Neuromuscular Disorders Clinical Trials I Ohio State Medical Center

ALS and Motor Neuron Disease

Purpose of the Study:

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS.

Eligibility Criteria:

Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS defined by revised El Escorial criteria.
Age 18 years or older.
Capable of providing informed consent and complying with study procedures, in the SI's opinion.
Time since onset of weakness due to ALS ≤ 36 months at the time of the Master Protocol Screening Visit.
Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time of the Master Protocol Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to pandemic related restrictions, Forced Vital Capacity (FVC).
Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are permitted in the study.
Participants must either not take edaravone or have completed at least one cycle of edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants are permitted in the study.
Participants must have the ability to swallow pills and liquids at the time of the Master Protocol Screening Visit and, in the SI's opinion, have the ability to swallow for the duration of the study.
Geographically accessible to the site.

Exclusion Criteria

Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to SI's judgment (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, or clinically significant laboratory abnormality or EKG changes). Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x 109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2, thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.
Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the SI's opinion.
Active cancer or history of cancer, except for the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years.
Use of investigational treatments for ALS (off-label use or active participation in a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior to the Master Protocol Screening Visit.
Exposure at any time to any gene therapies under investigation for the treatment of ALS (off-label use or investigational).
If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or of child-bearing potential and unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
Anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the SI's opinion.
If a participant is being re-screened, the disqualifying condition has not been resolved, or the mandatory wash-out duration has not occurred.
For those participating in the optional CSF collection, contraindication to undergoing a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be currently taking anticoagulation medications such as warfarin that would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed.

Link:

https://clinicaltrials.gov/ct2/show/NCT04297683?term=Platform+Trial&cond=ALS&draw=2&rank=1#eligibility

Sponsor:

Merit E. Cudkowicz, MD

Purpose:

The ASSESS ALL ALS protocol is a combined longitudinal natural history and biomarker study collecting a wide range of samples, clinical information and outcome measurements for future research into ALS and related neurological diseases. This study is designed to include all people diagnosed with ALS and control participants.

Inclusion Criteria for ALS Participants:

Age 18 years or older
Capable of providing informed consent
Willing to follow study procedures
Diagnosis of ALS by a physician
Access to a smartphone, computer or tablet, and internet (need not be in the home — access to a public library or other available computer with internet connection is sufficient)

Inclusion Criteria for control participants:

Age 18 years or older
Capable of providing informed consent
Willing to follow study procedures
No diagnosis of ALS , Progressive Muscular Atrophy (PMA) or Primary Lateral Sclerosis (PLS)
No history of familial ALS/Frontotemporal Dementia (FTD) in a close family member1 unless the participant has previously tested negative for the known causative ALS genes. Participants with a family history of singleton ALS are permitted to enroll. Defined by the presence of a known ALS causative gene such as C9orf72 in a family member or a family history suggestive of an inherited ALS/FTD syndrome defined by two family members with a history of ALS and/or FTD.
Access to a smartphone, computer or tablet, and internet (need not be in the home - access to a public library or other available computer with internet connection is sufficient)

Exclusion Criteria for all participants:

Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, active suicidal ideation, suicide attempt, or untreated major depression <= 90 days of screening, that would interfere with the study procedure, according to Investigator’s judgement.
Clinically significant unstable medical condition (other than ALS) (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, malignant and potentially progressive cancer) that would render the participant unlikely to be able to complete 12 months of follow-up, according to Investigator’s judgment.

Exclusion Criteria for participants undergoing optional Lumbar Puncture:

Medically unable to undergo lumbar puncture (LP) as determined by the site investigator (i.e., bleeding disorder, a skin infection at or near the LP site, known or suspected intracranial or intraspinal tumor or other cause of increased intracranial pressure).
Allergy to Lidocaine or other local anesthetic agents.
Use of anticoagulant medication or antiplatelet medications (aside from aspirin 81 mg) that cannot be safely withheld prior to lumbar puncture.
Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.
Current pregnancy based on participant self-report.
Clinical judgement of the site investigator that the participant would be unable to undergo multiple lumbar punctures.

Link to the study

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Purpose:

The PREVENT ALL ALS protocol is a longitudinal natural history and biomarker study for individuals genetically at risk for ALS/FTD. Through collecting a wide range of samples, clinical information and outcome measurements, the study aims to characterize pre-symptomatic ALS/FTD disease states. This trial also aims to identify genetically at risk individuals by offering genetic counseling and testing in an optional Sub-study.

Inclusion for PREVENT ALL ALS:

Age 18 years or older
Capable of providing informed consent
Willing to follow study procedures
First-degree relative of a known carrier of any ALS causative gene1 (regardless of whether ALS or FTD has actually been symptomatic in the family)

First-degree relative of an individual with ALS and/or FTD in a family with a “compelling family history” of ALS/FTD, regardless of whether genetic testing has occurred in symptomatic family members. A “compelling family history” is defined as a pedigree with at least 2 close relatives who had ALS or FTD, with at least one of those family members having had ALS.
Access to a smartphone, computer, or tablet, and internet (need not be in the home – access to a public library or other available computer with internet connection is sufficient)

Exclusion Criteria for PREVENT ALL ALS:

Evidence of neurological signs or symptoms concerning for ALS of FTD, at the discretion of the site investigator which will be communicated to the applicant along with referral for appropriate clinical follow-up.
Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, active suicidal ideation, suicide attempt, or untreated major depression <= 90 days (about 3 months) of screening, which in the opinion of the Investigator would interfere with the study procedures
Clinically significant, unstable medical condition (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, malignant and potentially progressive cancer) that would render the participant unlikely to be able to complete 12 months of follow-up, according to Investigator's judgment

Exclusion Criteria for Participants Undergoing Optional Lumbar Puncture:

Medically unable to undergo lumbar puncture (LP) as determined by the site investigator (i.e., bleeding disorder, a skin infection at or near the LP site, known or suspected intracranial or intraspinal tumor or other cause of increased intracranial pressure).
Allergy to Lidocaine or other local anesthetic agents.
Use of anticoagulant medication or antiplatelet medications (aside from aspirin 81 mg) that cannot be safely withheld prior to lumbar puncture.
Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.
Current pregnancy based on participant self-report
Clinical judgement of the site investigator that the participant would be unable to undergo multiple lumbar punctures.

Inclusion Criteria for Genetic Testing Results Sub-study:

Age 18 years of age or older
Capable of providing informed consent
Willing to follow study procedures
Currently enrolled in the PREVENT ALS Study

1 Gene Eligibility Criteria: Gene is ranked as ClinGen Definitive or Strong Classification and Variant is Classified as Pathogenic or Likely Pathogenic by ACMG Criteria. If only the gene and not the specific variant is known to the participant, they are eligible if the gene is ranked as Definitive or Strong. If gene is not Definitive or Strong classification or Variant is classified as a variant of uncertain significance, participant’s eligibility must be submitted for adjudication by PREVENT study team.

Exclusion Criteria for Genetic Testing Sub-Study:

Presence of unstable psychiatric illness (psychosis, active suicidal ideation, suicide attempt, or untreated major depression) in whom predictive genetic testing would confer a high risk of harm, at the discretion of the site investigator

Link to the study

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Purpose:

ION363 is an intrathecally administered ASO drug targeted to a specific sequence of the FUS RNA transcript and prevent production of FUS protein. The purpose of this study is the efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with amyotrophic lateral sclerosis (FUS-ALS).

Inclusion Criteria for Part 1:

Must provide written informed consent (and assent, if indicated per patient’s age and institutional guidelines) (signed and dated) and any authorizations required by local law.
At the time of informed consent, a patient must be ≥ 10 years of age and have signs or symptoms consistent with an ALS disease process (in the opinion of the Investigator).
Genetic mutation in FUS confirmed by a testing laboratory that is CLIA-certified and CE-marked, or equivalent. Mutations must be reviewed and approved by a Variant Classification Committee.
Upright (sitting position) SVC is ≥ 50% of predicted value (as adjusted for sex, age, and height) OR if SVC is < 50% of predicted value, must be 10 to 30 years of age (inclusive) at the time of informed consent AND had ALS symptom onset within 12 months before the time of informed consent
Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, assessments, and visits.
A patient who is taking edaravone, riluzole, Relyvrio (sodium phenylbutyrate/taurursodiol combination, called Albrioza in Canada), sodium phenylbutyrate, or tauroursodeoxycholic acid (TUDCA, also known as taurursodiol or urosodiol) must be on a stable dose for ≥ 28 days prior to Day 1 and willing to continue on that dose throughout the duration of the study, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
Satisfies the following:

A female must not be pregnant or lactating and must fulfill one of the following:

is surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or vasectomized male partner)
is postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
is abstinent* or
if engaged in sexual relations of childbearing potential, agrees to use a highly effective contraceptive method (refer to Section 6.3.1) from the time of signing the ICF until at least 40 weeks after the last dose of Study Drug

A male must be abstinent*, be surgically sterile (had a vasectomy with negative semen analysis at follow-up or has a surgically sterile non-pregnant female partner), or if engaged in sexual relations with a woman of childbearing potential (WOCBP), agree to use a highly effective contraceptive method (refer to Section 6.3.1) from the time of signing the ICF until at least 40 weeks after the last dose of Study Drug.

* Only true abstinence (i.e., abstinence in line with the preferred and usual lifestyle of the patient) is acceptable. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.

Stable concomitant medications and nutritional support for at least 1 month prior to Study Day 1. Concomitant medications or nutritional support that have not been stable for at least 1 month prior to Study Day 1 may be allowed per Investigator judgment.
Has an informant/caregiver who, in the Investigator’s judgment, has frequent and sufficient contact with the patient to be able to provide accurate information about the patient’s cognitive and functional abilities throughout the study. In addition, a patient who is < 18 years old must have a trial partner (parent, caregiver, or other) who is reliable, competent, at least 18 years of age, and willing to accompany the patient to all trial visits.

Inclusion Criteria for Part 2:

Completed or was rescued from Part 1, or enrolled and received at least 1 dose of ION363 in the IIS. Patients from the IIS must provide written informed consent (and assent, if indicated per patient’s age and institutional guidelines) (signed and dated) and any authorizations required by local law.
Satisfies the following:

A female must not be pregnant or lactating and must fulfill one of the following:

is surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or vasectomized male partner)
is postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
abstinent* or
if engaged in sexual relations of childbearing potential, agrees to use a highly effective contraceptive method (refer to Section 6.3.1) from the time of signing the ICF until at least 40 weeks after the last dose of Study Drug

A male must be abstinent*, be surgically sterile (had a vasectomy with negative semen analysis at follow-up or has a surgically sterile non-pregnant female partner), or if engaged in sexual relations with a WOCBP, agrees to use a highly effective contraceptive method (refer to Section 6.3.1) from the time of signing the ICF until at least 40 weeks after the last dose of Study Drug.

Is suitable for study participation, in the opinion of the Investigator

Exclusion Criteria for Part 1:

Requires permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days) or tracheostomy
Any known genetic variant (other than those in the FUS gene) that is pathogenic or likely to be pathogenic for the ALS–frontotemporal dementia (FTD) spectrum of disease
Positive test result for:

Human immunodeficiency virus (HIV)
Hepatitis C (HCV), unless previously treated and has been serum/plasma HCV RNA negative for at least 6 months after the end of treatment
Hepatitis B (HBV) by HBV surface antigen test, unless currently on nucleotide/nucleoside analogue treatment

Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 3 months before Screening, major surgery within 2 months before Screening) or physical examination
Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
Uncontrolled hypertension (BP > 160/100 mmHg)
Malignancy within 1 year before Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and have not recurred within 6 months may also be eligible per Investigator judgment.
Obstructive hydrocephalus
Presence of a functional ventriculoperitoneal shunt for the drainage of CSF or an implanted CNS catheter
Known significant brain or spinal disease that would interfere with the LP procedure, CSF circulation, or safety assessment, including tumors or abnormalities by MRI or computed tomography (CT), subarachnoid hemorrhage, suggestion of raised intracranial pressure on MRI or ophthalmic examination, spinal stenosis or curvature, Chiari malformation, obstructive hydrocephalus, syringomyelia, tethered spinal cord syndrome, and connective tissue disorders such as Ehlers-Danlos syndrome and Marfan syndrome
Presence of significant cognitive impairment, not due to a developmental disability, based on the Mini-Mental State Examination (MMSE) (score of < 20) or an equivalent assessment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression, as determined by the Investigator
Concurrent participation in any other interventional clinical study
Previous or current treatment with any other oligonucleotide (including small interfering RNA [siRNA], tofersen). This exclusion criterion does not apply to coronavirus disease 2019 (COVID-19) vaccinations, which are allowed.
Treatment with another investigational drug, biological agent, or device within 1 month before Screening or 5 half-lives of the investigational agent, whichever is longer
History of gene therapy or cell transplantation or any other experimental brain surgery
Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication that cannot be safely paused before and/or after an LP procedure according to local or institutional guidelines and/or Investigator determination after consultation with the appropriate treating physician. Low-dose aspirin (≤ 100 mg/day, administered as monotherapy) is permitted and may be continued through the LP procedure.
Clinically significant low platelet count (defined as < 100,000/mm3), coagulation tests, or laboratory abnormalities that would render a patient unsuitable for inclusion
Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
Has any other conditions that would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study, in the opinion of the Investigator

No additional exclusion criteria are specified for Part 2.

Link to the study

Sponsor: Ionis Pharmaceuticals, Inc.

Ataxia

Purpose of the Study: Friedreich's ataxia is an autosomal recessive cerebellar ataxia caused by triplet-repeat expansions. The causative mutation is a trinucleotide (GAA) repeat expansion in the first intron of the frataxin gene, leading to impaired transcription of frataxin. The pathological consequences of frataxin deficiency include a severe disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation, and an increased sensitivity to oxidative stress.

A hallmark of Friedreich's ataxia is impairment of antioxidative defense mechanisms, which play a major role in disease progression. Studies have demonstrated that nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling is grossly impaired in patients with Friedreich's ataxia. Therefore, the ability of omaveloxolone (RTA 408) to activate Nrf2 and induce antioxidant target genes is hypothesized to be therapeutic in patients with Friedreich's ataxia. This 2-part study will evaluate the efficacy, safety, and pharmacodynamics of omaveloxolone (RTA 408) in the treatment of patients with Friedreich's ataxia.

Key Inclusion Criteria:

Have genetically confirmed Friedreich's ataxia
Have a modified FARS score ≥20 and ≤80
Be male or female and ≥16 years of age and ≤40 years of age
Have no changes to exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the 16-week study period
Have the ability to complete maximal exercise testing
Be able to swallow capsules

Key Exclusion Criteria:

Have uncontrolled diabetes (HbA1c >11.0%)
Have B-type natriuretic peptide value >200 pg/mL
Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease
Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
Have known or suspected active drug or alcohol abuse
Have clinically significant abnormalities of clinical hematology or biochemistry, including but not limited to elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase, or alanine aminotransferase
Have any abnormal laboratory test value or serious pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study enrollment
Have taken any of the following drugs within 7 days prior to Study Day 1 or plan to take any of these drugs during the time of study participation:
Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g., carbamazepine, phenytoin, ciprofloxacin, grapefruit juice)
Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
Have participated in any other interventional clinical study within 30 days prior to Study Day 1
Have a cognitive impairment that may preclude ability to comply with study procedures
Prior participation in a trial with omaveloxolone (RTA 408)

Study Status: Active, not recruiting.

Sponsor: Reata Pharmaceuticals, Inc.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Fascioscapulohumeral Muscular Dystrophy (FSHD)

Purpose of the Study: This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks.

Key Inclusion Criteria:

The patient must have consented to participate and must have provided signed, dated and witnessed IRB-approved informed consent form that conforms to federal and institutional guidelines.
Male or female subjects
Patients must be between 18 and 65 years of age, inclusive
Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy.
Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening
Must have a MRI-eligible muscle for biopsy
Must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
Will practice an approved method of birth control

Key Exclusion Criteria:

Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.
Acute or chronic history of liver disease or known to have current alanine aminotransferase ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C.
Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2).
Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2.
Male subjects with a female partner who is planning to become pregnant during the study or within 90 days after the last dose of study drug.
Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a study with an investigational product. Note: concurrent participation in other non-drug studies may be acceptable if confirmed in writing by the sponsor.

Study Status: Completed

Sponsor: Fulcrum Therapeutics

Purpose of the Study: This study is an open-label extension to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.

Key Inclusion Criteria:

The patient must have consented to participate and must have provided signed, dated and witnessed an IRB-approved informed consent form that conforms to federal and institutional guidelines.
Male or female subjects
Patients must be between 18 and 65 years of age, inclusive
Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy.
Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening
Must have a MRI-eligible muscle for biopsy
Must be will and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
Will practice an approved method of birth control

Key Exclusion Criteria:

Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.
Acute or chronic history of liver disease or known to have current alanine aminotransferase ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C.
Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2).
Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2.
Male subjects with a female partner who is planning to become pregnant during the study or within 90 days after the last dose of study drug.
Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a study with an investigational product. Note: Concurrent participation in other non-drug studies may be acceptable if confirmed in writing by the sponsor.

Study Status: Enrolling by invitation.

Sponsor: Fulcrum Therapeutics

Myotonic Dystrophy Type 1

Purpose of the Study: Building on previous work of the Myotonic Dystrophy Clinical Research Network (DMCRN), the present study seeks to overcome insufficient data on natural history; lack of reliable biomarkers; and incomplete characterization and limited biological understanding of the phenotypic heterogeneity of Myotonic Dystrophy 1 by examining strategies to improve the reliability by making further refinements in our sample collection and analysis procedures by developing strategies for managing patient heterogeneity going forward.

Key Inclusion Criteria:

Age 18 to 70 (inclusive)
Competent to provide informed consent
Clinical diagnosis of DM1 based on research criteria1 or positive genetic test
Comment: The clinical research criteria require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in > 99% of individuals who satisfied these criteria
Of the 95 patients undergoing the tibialis anterior muscle biopsy, at least half will have at least moderate weakness of ankle dorsiflexion, defined as MRC score ≤ 4+. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy. Approximately 10 patients at each site will undergo the muscle biopsy.

Key Exclusion Criteria:

Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than skin cancer.
Current alcohol or substance abuse
Concurrent enrollment in clinical trial for DM1, or participation in trial within 6 months of entry.
Concurrent pregnancy or planned pregnancy during the course of the study.
Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator, compromise performance on study measures.
Note: non-ambulatory participants are not excluded, but are limited to <15% of enrollment.
Known CTG repeat expansion size less than 100 repeats, unless there are clear cut signs of limb weakness and muscle wasting. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy.
Use of anticoagulant such as warfarin or a direct oral anticoagulant (e.g. dabigatran) due to the increased risk of bleeding.
Use of aspirin or non-steroidal anti-inflammatory agents should be discontinued 3 days prior to the biopsy procedure, if possible.
Platelet count <50,000 (if known) due to the increased risk of bleeding.
History of a bleeding disorder due to the increased risk of bleeding.
Advanced wasting of tibialis anterior (TA) muscle that precludes needle muscle biopsy in order to ensure that a sample taken would be of muscle and not just fat and fascia.
Previous muscle biopsy of either TA in order to provide muscle tissue samples of non-biopsied muscles.

Study Status: Enrolling by invitation.

Sponsor: Virginia Commonwealth University

Other Conditions

Purpose of the Study: THAOS is a global, multi-center, longitudinal observational survey open to all patients with transthyretin amyloidosis (ATTR), including ATTR-PN (polyneuropathy), ATTR-CM (cardiomyopathy) and wild-type ATTR-CM. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate. The principal aims of this outcome survey are to better understand and characterize the natural history of the disease by studying a large and heterogenous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.

Key Inclusion Criteria:

Evidence of a personally signed and dated informed consent document indicating that the participant (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Males and females greater than or equal to 18 years of age.
Confirmed genotyped TTR mutation with or without a diagnosis of hereditary or wild-type ATTR amyloidosis. Confirmation of ATTRwt amyloidosis will be determined by genotyped confirmation that patient does not possess a known mutation in TTR gene (ie, is a carrier of wild-type allele only) via genetic testing and one of the following set of criteria (a, b, or c):
Presence of amyloid in cardiac biopsy tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or
Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in non-cardiac tissue confirmed as TTR amyloid by mass spectrometry or immunohistochemistry; or
Evidence of cardiac involvement by echocardiogram as defined by left ventricle wall thickness of >12 mm, and presence of amyloid in cardiac tissue indirectly confirmed by scintigraphy with a "bone seeking tracer" eg, 99mTC-DPD [99mTC-3,3-diphosphono-1,2-propano-dicarboxylic acid], 99mTC- PYP [Pyrophosphate], and 99mTC-HMDP [hydroxymethylene diphosphonate] with Perugini grade greater than or equal to 2.

Key Exclusion Criteria:

Patient has evidence of primary (light chain) or secondary amyloidosis.

Study Status: Recruiting.

Sponsor: Pfizer

Purpose of the Study: The TopCSPN trial is a double blinded randomized placebo controlled study of oral topiramate as a potential disease modifying therapy for cryptogenic sensory peripheral neuropathy (CSPN). Patients with CSPN who also have metabolic syndrome (defined by the ATPIII criteria) who do not have an alternative cause for neuropathy will be potentially eligible. The co primary outcome measures are change in the Norfolk Quality of Life - Diabetic Neuropathy (NQOL-DN) Scale and intraepidermal nerve fiber density (IEFND) at the distal thigh. The treatment phase will last 24 months.

Key Inclusion Criteria:

Age 18-80
Diagnosis of confirmed symptomatic distal symmetric peripheral polyneuropathy based on the Toronto consensus criteria for probable neuropathy (the presence of unequivocal signs and symptoms of neuropathy)45.
Evidence of symptomatic neuropathy based on a screening visit NQOL-DN score of >9.
Metabolic syndrome based on modified ATPIII criteria. Specific criteria require 3 of the following 6 to be present at the screening visit.
Waist circumference >102 cm for men, >88 cm for women
Serum triglycerides of > 150 mg/dl
HDL < 40 mg/dl for men, < 50 mg/dl for women
Those with either a normal HDL or TRG who are taking a lipid lowering medication for this purpose
Blood pressure 130/85 mm Hg or use of anti-hypertension drug
Hyperglycemia based on American Diabetes Association (ADA) criteria at screening based on any one or more of the following: fasting plasma glucose > 100 mg/dL (5.6 mmol/L), 2-hour glucose tolerance test > 140 mg/dL (7.8 mmol/L), or hemoglobin A1c > 5.7% .
No current or prior history of therapy with topiramate.
If female of child-bearing potential (i.e., not surgically sterile or post-menopausal defined as age > 51 years without menses for ≥ 2 years), negative serum pregnancy test at screening and negative urine pregnancy test at baseline visit.
Women of child-bearing potential or men with sexual partners of childbearing potential be willing to use an acceptable method of birth control for the duration of the study and for 12 weeks following completion of study drug therapy. Acceptable methods of birth control include abstinence, oral contraceptives, the contraceptive patch, intra-uterine device, the contraceptive ring, and or barrier contraception such as condoms with spermicide.

Key Exclusion Criteria:

CSS-PI clinical determination of an alternative cause for peripheral neuropathy (including but not limited to rheumatological disorders, Hepatitis B or C, breast cancer treated with neurotoxic chemotherapy within the past 15 years). All potential subjects will have screening neuropathy labs including assessment for diabetes (Hemoglobin A1c, oral glucose tolerance test), vitamin B12 level, and immunofixation47.
Type I diabetes or current use of insulin or use of insulin in the past 3 months.
HgA1c > 7.5%. Borderline screening labs can be repeated within two weeks with PPI approval.
History of recurrent nephrolithiasis, a single episode of nephrolithiasis within one year prior to screening, or use of ongoing preventative treatment.
Family history of a hereditary neuropathy in a first-degree relative.
Severe neuropathy: Utah Early Neuropathy Score > 24 at screening
Active foot ulceration or a history of a nontraumatic foot amputation.
ECG with QTc more than 450 ms in men, or 470 ms in women.
Risk of excessive bleeding at the skin biopsy site based on the clinical assessment of the CSS-PI.
Chronic corticosteroid use excluding topical or inhaled treatment.
Use of a carbonic anhydrase inhibitor (such as acetazolamide) due to risk of nephrolithiasis.
Planned bariatric surgery.
Use of other weight loss medications.
Use of scheduled opiates, or as needed opiate medications more than three times weekly.
Use of topical capsaicin products within 16 weeks of screening or at any time on study.
Medication change for neuropathy symptoms during the 8 weeks prior to screening; or anticipated change for the duration of study participation.
Current use of an intrathecal pain pump or spinal cord stimulator.
Screening laboratory creatinine ≥ 2.0 mg/dl.
Severe edema, dermatologic or lower extremity condition that would increase risk of skin biopsy.
Major depression, bipolar affective disorder, or other mental health disorders that are sufficiently severe to increase adverse event risk or impact neuropathy assessment in the opinion of the responsible site principal investigator.
Current suicidal ideation within one year prior to the baseline visit as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS).
Ataxia sufficiently severe to represent an unacceptable fall risk in the opinion of the site principal investigator.
A serious medical condition expected to dramatically shorten life span or prevent participation.
Any clinically significant condition or illness, which, in the opinion of the CSS-PI, would pose a risk to the subject or might confound the study including metabolic acidosis, bone marrow suppression, blood dyscrasias, bleeding disorder, or closed angle glaucoma.
History of alcohol or drug abuse within the past two years, or existing neuropathy related to past drug or alcohol abuse.
History of malignancy within five years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
A history of epilepsy.
An inability to understand or cooperate with the procedures of the study.
Pregnant, or intending to become pregnant, or breastfeeding.

Study Status: Active, not recruiting.

Sponsor: Virginia Commonwealth University

Purpose of the Study: To evaluate the safety and efficacy of intravenous onasemnogene abeparvovec-xioi in pre-symptomatic patients with SMA and 2 or 3 copies SMN2

Key Inclusion Criteria:

Age ≤6 weeks (≤42 days) at time of dose
Ability to tolerate thin liquids as demonstrated through a formal bedside swallowing test
Compound muscle action potential (CMAP) ≥2mV at Baseline; centralized review of CMAP data will be conducted
Gestational age of 35 to 42 weeks
• Patients with pre-symptomatic SMA Type 1 as determined by the following features:
2 copies of SMN2 Patients with 2 copies of SMN2 (n ≥12)
• Patients with pre-symptomatic SMA Type 2 as determined by the following features:
3 copies of SMN2

Key Exclusion Criteria:

Weight at screening visit <2 kg
Hypoxemia (oxygen saturation <96% awake or asleep without any supplemental oxygen or respiratory support) at the screening visit or for altitudes >1000 m, oxygen saturation <92% awake or asleep without any supplemental oxygen or respiratory support at the screening visit
Any clinical signs or symptoms at screening or immediately prior to dosing that are, in the opinion of the Investigator, strongly suggestive of SMA
Tracheostomy or current prophylactic use or requirement of noninvasive ventilatory support at any time and for any duration prior to screening or during the screening period
Patients with signs of aspiration/inability to tolerate nonthickened liquids based on a formal swallowing test performed as part of screening or patients receiving any non-oral feeding method
Clinically significant abnormalities in hematology or clinical chemistry parameters as determined by investigator or medical monitor
Treatment with an investigational or commercial product, including nusinersen, given for the treatment of SMA. This includes any history of gene therapy, prior antisense oligonucleotide treatment, or cell transplantation.
Patients whose weight-for-age is below the third percentile based on World Health Organization (WHO) Child Growth Standards
Biological mother with active viral infection as determined by screening laboratory samples (includes human immunodeficiency virus [HIV] or positive serology for hepatitis B or C)
• Biological mothers with clinical suspicion of Zika virus that meet Centers for Disease Control and Prevention (CDC) Zika virus epidemiological criteria including history of residence in or travel to a geographic region with active Zika transmission at the time of travel will be tested for Zika virus RNA. Positive results warrant confirmed negative Zika virus RNA testing in the patient prior to enrollment.
Serious nonrespiratory tract illness requiring systemic treatment and/or hospitalization within 2 Weeks prior to screening
Upper or lower respiratory infection requiring medical attention, medical intervention, or increase in supportive care of any manner within 4 Weeks prior to dosing
Severe nonpulmonary/respiratory tract infection within 4 Weeks before administration of gene replacement therapy or concomitant illness that, in the opinion of the Investigator or Sponsor medical monitor, creates unnecessary risks for gene replacement therapy such as:
Major renal or hepatic impairment
Known seizure disorder
Diabetes mellitus
Idiopathic hypocalciuria
Symptomatic cardiomyopathy
Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
Previous, planned or expected major surgical procedure including scoliosis repair surgery/procedure during the study assessment period
Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, immunosuppressive therapy within 4 Weeks prior to gene replacement therapy
AntiAAV9 antibody titer >1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay
• Should a potential patient demonstrate AntiAAV9 antibody titer >1:50, he or she may receive retesting inside the 30-Day screening period and will be eligible to participate if the AntiAAV9 antibody titer upon retesting is ≤1:50, provided the <6 Week age requirement at the time of dosing is still met
Biological mother involved with the care of the child refuses anti-AAV9 antibody testing prior to dosing

Study Status: Active, not recruiting.

Sponsor: Novartis Gene Therapies

Purpose of the Study: Anti-myelin-associated glycoprotein (MAG) is a rare autoimmune disorder of the peripheral nerves that presents with weakness, gait imbalance, and loss of sensation. It almost always occurs in the setting of excess protein buildup in the body in the form of immunoglobulin monoclonal (IgM) gammopathy. Anti-MAG neuropathy currently has no established therapies. It is diagnosed through blood tests (anti-MAG and IgM), nerve conduction studies (which showed marked velocity slowing), and clinical exam findings.The efficacy of lenalidomide has been demonstrated in anti-MAG peripheral neuropathy with two separate dosing regimens: 25mg on days 1-21 of each 28 day cycle in conjunction with oral dexamethasone 20mg/day on days 1-4 of each cycle as well as at 5mg on days 1-21 of each cycle without oral dexamethasone. This phase 1 study aims to determine the maximum tolerated dose (MTD) of Lenalidomide in patients with anti-MAG neuropathy. We will explore preliminary efficacy and postulate that this drug is effective in this subset of patients, using preselected, specifically tailored outcome measures that encompass quality of life, neurologic function, serum protein levels, and focused measures of proprioception.

Key Inclusion Criteria:

Patients must have Distal acquired demyelinating sensorimotor (DADS) peripheral neuropathy phenotype as defined per European Federation of Neurological Societies (EFNS) demyelinating criteria with preferential distal nerve involvement, as captured per terminal latency index [terminal distance/(conduction velocity x terminal latency)], in the setting of a monoclonal gammopathy
Patients must be at least 18 years of age with no evidence of multiple myeloma, light chain amyloidosis or other hematologic disorder requiring treatment.
Patient may be enrolled at any time from last line of therapy.
Patients must have ANC > 1000/µL and Platelets ≥75,000/µL
Patients must have adequate hepatic function as evidenced by: total bilirubin < 1.5 mg/dL, alkaline phosphatase < 3X the ULN, and AST/ALT < 2X the ULN.
Patients must be able to take any of the following once lenalidomide starts and for at least 5 days after last dose lenalidomide: 1) 81-325 mg of coated aspirin daily; 2) full dose warfarin (target INR 2-3); 3) 2.5 mg or above of apixaban twice daily; 4) low molecular weight heparin; 5) 20 mg or above of rivaroxaban daily.
Patients must have adequate renal function as evidenced by serum creatinine < 2mg/dL or calculated creatinine clearance of ≥ 40ml/min within 14 days of registration using MDRD formula.
Patient must be able to swallow capsule or tablet.
Patients must provide informed consent.
All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
Two negative pregnancy tests will be required for all women of child bearing potential, with the second negative test having been at least 7 days prior to starting the study drug. Breast feeding is not permitted.
Fertility requirements
Female patients with child bearing potential must have two negative pregnancy tests, with the second negative test having been at least 7 days prior to starting the study drug.
Male patients must agree to use an adequate method of contraception starting from screening to 90 days after stopping the drug.
Female patients must be either posy-menopausal, free from menses ≥2 yrs., surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from sexual activity starting from screening to 90 days after stopping the drug.
Female patients of child bearing potential must agree to comply with the fertility and pregnancy test requirements dictated by the Rev-Assist program.

Key Exclusion Criteria:

Patient with concurrent hematologic or oncologic malignancy requiring systemic treatment
History of allergic reaction (including erythema nodosum) to lenalidomide
Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
Patients with a history of gastrointestinal surgery or other procedure that might, in the opinion of the investigator(s), interfere with the absorption or swallowing of the study drugs.
Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff.
Any other medical condition, including mental illness or substance abuse deemed by the investigator(s) to likely interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.

Study Status: Recruiting.

Sponsor: Ohio State University

Purpose of the Study: This is a phase 3 double-blind randomized study to study the efficacy and safety of intravenous ATB200 Co-administered with oral AT2221 in adult subjects with Late Onset Pompe Disease compared with Alglucosidase Alfa/placebo.

Key Inclusion Criteria:

Subject must provide signed informed consent prior to any study-related procedures being performed.
Male and female subjects are ≥ 18 years old and weigh ≥ 40 kg at screening.
Female subjects of childbearing potential and male subjects must agree to use medically accepted methods of contraception during the study and for 90 days after the last dose of study drug.
Subject must have a diagnosis of LOPD based on documentation of one of the following:
deficiency of GAA enzyme
GAA genotyping
Subject is classified as one of the following with respect to ERT status:
ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for ≥ 24 months
ERT-naïve, defined as never having received investigational or commercially available ERT
Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:
both screening values of 6MWD are ≥ 75 meters
both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults
the lower value of 6MWD is within 20% of the higher value of 6MWD

Key Exclusion Criteria:

Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before Day 1 or is anticipated to do so during the study.
Subject has received gene therapy for Pompe disease
Subject is taking any of the following prohibited medications within 30 days before Day 1:
miglitol (eg, Glyset)
miglustat (eg, Zavesca)
acarbose (eg, Precose or Glucobay)
voglibose (eg, Volix, Vocarb, or Volibo)
Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days.
Subject requires the use of invasive or noninvasive ventilation support for > 6 hours per day while awake.
Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221.
Subject has a medical condition or any other extenuating circumstance that may, in the opinion of the investigator or medical monitor, pose an undue safety risk to the subject or may
compromise his/her ability to comply with or adversely impact protocol requirements. This includes clinical depression (as diagnosed by a psychiatrist or other mental health professional) with uncontrolled or poorly controlled symptoms.
Subject, if female, is pregnant or breastfeeding at screening.
Subject, whether male or female, is planning to conceive a child during the study.
Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing.

Study Status: Completed.

Sponsor: Amicus Therapeutics

Purpose of the Study: This is a single center, 22-month observational study of nusinersen treatment in adult patients with spinal muscular atrophy (SMA). There will be a total of seven visits. Nusinersen is provided as standard of care and not considered research in this study. Information will be collected regarding the general health, and function including muscle strength of, as well as any positive and/or adverse events experienced by the study participants.

Key Inclusion Criteria:

Age 18 to 60 years
Genetic confirmation of 5q SMA documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder
SMN2 copy number of 3 or greater
Subjects must be able to walk thirty feet without assistance (i.e. no canes, walkers)
Interest in participating and the ability to meet the study requirements
Women of childbearing-age are required to be on birth control or abstain while participating in the research study

Key Exclusion Criteria:

Subjects with history of spinal disease that will interfere with the lumbar puncture procedure
Subjects with history of bacterial meningitis or encephalitis
Subjects with history of use of investigational drug treatment for SMA in the last six months, or plan on enrolling in any other treatment trial during the duration of this trial
History of treatment with gene therapy, stem cell or antisense oligonucleotide
Patients with co-morbid conditions that preclude travel, testing or study medications
Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing
Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding

Study Status: Active, not recruiting.

Sponsor: Ohio State University

Key Inclusion Criteria:

Age 18 to 60 years
Genetic confirmation of 5q SMA documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder
SMN2 copy number of 3 or greater
Subjects must be able to walk thirty feet without assistance (i.e. no canes, walkers)
Interest in participating and the ability to meet the study requirements
Women of childbearing-age are required to be on birth control or abstain while participating in the research study

Key Exclusion Criteria:

Subjects with history of spinal disease that will interfere with the lumbar puncture procedure
Subjects with history of bacterial meningitis or encephalitis
Subjects with history of use of investigational drug treatment for SMA in the last six months, or plan on enrolling in any other treatment trial during the duration of this trial
History of treatment with gene therapy, stem cell or antisense oligonucleotide
Patients with co-morbid conditions that preclude travel, testing or study medications
Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing
Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding

Study Status: Active, not recruiting.

Sponsor: Ohio State University

Refractory Generalized Myasthenia Gravis (GMG)

Purpose of the Study: The purpose of the MycarinGstudy is to demonstrate the clinical efficacy and to assess safety and tolerability of rozanolixizumab in patients with generalized myasthenia gravis (MG).

Key Inclusion Criteria:

Study participant must be ≥18 years of age, at the time of signing the informed consent
Study participant has documented diagnosis of generalized myasthenia gravis (gMG) at Visit 1, based on study participant's history and supported by previous evaluations
Study participant has a confirmed positive record of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) at Screening (Visit 1).The presence of autoantibodies may be confirmed with repeat testing at Visit 1
Study participant has Myasthenia Gravis Foundation of America (MGFA) Class II to IVa at Visit 1
Study participant with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 3 (with ≥3 points from non-ocular symptom) AND a quantitative myasthenia gravis (QMG) score of at least 11 at Visit 1 and at Baseline (Visit 2)
Study participant is considered for additional treatment such as intravenous immunoglobulin g (IVIg) or plasma exchange (PEX) by the Investigator

Key Exclusion Criteria:

Study participant has a known history of hyperprolinemia
Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) in the opinion of the Investigator, or had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of investigational medicinal product (IMP)
Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial infection (NTMBI) will be excluded
Study participant has experienced hypersensitivity reaction after exposure to other anti-neonatal Fc receptor (FcRn) drugs
Study participant with severe (defined as Grade 3 on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis at Visit 1 or Visit 2
Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrow transplant

Study Status: Recruiting.

Sponsor: UCB Biopharma SRL

Purpose of the Study: Myasthenia gravis is an autoimmune condition that causes muscle weakness. Autoimmune means the body makes antibodies that attack its own cells and tissues. These types of antibodies are also known as autoantibodies. People with generalized myasthenia gravis have a weakness in many muscles. TAK-079 is a medicine to help people with generalized myasthenia gravis. The main aim of this study is to check if people with generalized myasthenia gravis have side effects from 2 doses of TAK-079. Other aims are to learn if TAK-079 improves their clinical condition and lowers their autoantibody levels.

Key Inclusion Criteria:

Diagnosis of Myasthenia Gravis (MG) supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening.
Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV at screening.
Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 6 or greater at screening, with at least 4 points attributed to nonocular items.
If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with stable dosing ongoing for at least 3 months before screening. Participants receiving azathioprine must be on a stable dose for at least 6 months before screening.
If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy, as opposed to pulse therapy.
If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening.
The doses of concomitant standard background therapy must be expected to remain stable throughout the study unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Participants must be on at least one allowed background medication.

Key Exclusion Criteria:

Presence of a thymoma (previous history of a fully encapsulated thymoma removed ≥ 12 months before screening is allowed) or history of invasive thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before screening.
History of thymectomy within 12 months before screening.
MGFA class I or V.
Received intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), or plasmapheresis/plasma exchange within 4 weeks before screening, or an expectation that any therapy besides the participants standard background therapies may be used for treatment of MG (eg, a rescue therapy) between screening and dosing.
Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
Note: FEV1 testing is required for participants suspected of having COPD or asthma.
Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 months before first dosing. Participants with prior exposure to rituximab must have CD19 counts within the normal range at screening.
Known autoimmune disease other than MG that could interfere with the course and conduct of the study.
Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study.
Opportunistic infection ≤12 weeks before initial study dosing or currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved without systemic therapy prior to Day 1.

Study Status: Recruiting.

Sponsor: Takeda

Sporadic Inclusion Body Myositis (IBM)

Purpose of the Study: Funding Source - FDA OOPD. The purpose of this study is to evaluate the safety and efficacy of the study drug, Arimoclomol in IBM patients.

Key Inclusion Criteria:

Meet any of the European Neuromuscular Centre Inclusion Body Myositis research diagnostic criteria 2011 categories for IBM
Demonstrate being able to arise from a chair without support from another person or device
Able to ambulate at least 20 ft/6 meters with or without assistive device. Once arisen from the chair, participant may use any walking device, i.e. walker/frame, can, crutches, or braces. They cannot be supported by another person and cannot use furniture or wall for support.
Body weight of >= 40 kg
Pre-menopausal women must have a negative pregnancy tst prior to dosing iwht study medication.
If a participant in the bimagrumab study, the participant must be off of the study medication for at least 6 months.
Able to give informed consent

Key Exclusion Criteria:

History of any of the following excludes subject participation in the study: chronic infection particularly HIV or Hepatitis B or C; cancer other than basal cell cancer less than five years prior; or other chronic serious medical illnesses.
Presence of any of the following on routine blood screening: WEB <3000; platelets < 100,000; hematocrit , 30%; BUN > 30 mg%; creatinine > 1.5 mg%; symptomatic liver disease with serum albumin < 3 g/dL.
History of most recent creatine kinase >15x the upper limit of normal without any other explanation besides IBM.
History of non-compliance with other therapies
Use of testosterone except for physiologic replacement doses in case of androgen deficiency. Participants must have documented proof of the androgen deficiency.
Coexistence of other disease that would be likely to affect outcome measures.
Drug or alcohol abuse within past three months
Participation in a recent drug study in the last 30 days prior to the screening visit or use of a biologic agent less than 6 months prior to the screening visit.
Women who are lactating or unwilling to use adequate method of birth control who are not surgically sterile. Adequate birth control includes use of intrauterine device, abstinence, or oral contraceptives or a double barrier method, e.g condom plas diaphragm will be necessary for both male and female participants.
Participants taking >7.5 mg prednisolone or equivalent or participants on IVIg or other immunosuppressants within the last 3 months.

Study Status: Completed

Sponsor: Orphazyme

Neuromuscular Disorders Clinical Trials

ALS and Motor Neuron Disease

HEALEY ALS Platform Trial

ASSESS ALL ALS - Longitudinal Biomarker Study for Symptomatic ALS and Control Participant

PREVENT ALL ALS - Longitudinal Biomarker Study for Participants Who Are Genetically At Risk for Amyotrophic Lateral Sclerosis (ALS)

FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)

Ataxia

RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe

Clinical Outcome Measures in Friedreich’s Ataxia

A Phase 2 Study of the Safety, Efficacy and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Fingolimod 0.5 Mg Administered Orally Once Daily Versus Placebo in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Fascioscapulohumeral Muscular Dystrophy (FSHD)

Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)

Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD) With Open-Label Extension (OLE)

Preclinical Trial Preparedness in Fascioscapulohumeral Muscular Dystrophy (FSHD)

A Placebo-Controlled, Randomized, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biological Activity of ATYR1940 in Adult Patients with Molecularly Defined Genetic Muscular Dystrophies

Myotonic Dystrophy Type 1

Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1)

A Phase 1/2a Blinded, Placebo-Controlled Study to Assess the Safety, Tolerability and Dose-Range Finding of Multiple Ascending Doses of ISIS 598769 Administered Subcutaneously to Adult Patients With Myotonic Dystrophy Type 1

A Multicenter Observational Study to Assess the Variability of Molecular Biomarkers and Clinical Measures in Patients With Myotonic Dystrophy Type 1

Other Conditions

Transthyretin Amyloidosis Outcome Survey (THAOS)

The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Who Have Already Been Treated With ALN-TTR02 (Patisiran)

Topiramate for Cryptogenic Sensory Peripheral Neuropathy in Metabolic Syndrome (CSPN) (TopCSPN)

Pre-Symptomatic Study of Intravenous Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for Patients With Multiple Copies of SMN2 (SPR1NT)

Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study

PROPEL Study - A Study Comparing ATB200/AT2221 With Alglucosidase/Placebo in Adult Subjects With LOPD

HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With LOPD

A Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of ATTRv Amyloidosis With a V122I or T60A Mutation

Adults With SMA Treated With Nusinersen

Adults With SMA Treated With Nusinersen

Genetic and Molecular Characterization of Inherited Neuropathies

A Double Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, Efficacy and Preliminary Dose-Response of BAF312 in Patients With Active Dermatomyositis

A Phase 3 Switchover Study of the Efficacy and Safety of BMN 701 (GILT-tagged Recombinant Human GAA) in rhGAA Exposed Subjects With Late-Onset Pompe Disease

Open-Label Trial of Ranolazine in Myotonia Congenita

A Two-Part, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of BVS857 in Patients With Spinal and Bulbar Muscular Atrophy (SBMA)

Transthyretin-Associated Amyloidosis Outcomes Survey (THAOS): A Global, Multi-Center, Longitudinal, Observational Survey of Patients With Documented Transthyretin (TTR) Mutations or Wild-Type TTR Amyloidosis

Refractory Generalized Myasthenia Gravis (GMG)

Safety and Efficacy Study of RA101495 in Subjects With Generalized Myasthenia Gravis

Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis

A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

Safety, Tolerability, and Efficacy of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE)

A Study of TAK-079 in People with Generalized Myasthenia Gravis

Open-Label Extension of Zilucoplan in Subjects With Generalized Myasthenia Gravis (RAISE-XT)

A Phase II Trial of Rituximab in Myasthenia Gravis

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (GMG)

A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacodynamics of Belimumab in Subjects With Generalized Myasthenia Gravis

Sporadic Inclusion Body Myositis (IBM)

Study of Arimoclomol in Inclusion Body Myositis (IBM)

Using Next Generation Sequencing to Unravel the Pathogenesis of Sporadic Inclusion Body Myositis (IBM) – The International IBM Consortium Genetic Study

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