Neuromuscular Disorders Clinical Trials

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)

OR

• 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 of the Study: This is a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early-stage ALS (within 2 years of ALS symptoms onset). The study comprises a core double-blind (DB) 40-week treatment period followed by an open label extension (OLE).

Key Inclusion Criteria:

• are 18 years of age or older
• male or female, if of childbearing potential, strict contraception required
• have ALS confirmed by the trial doctors using different tests.
• have mild symptoms of ALS as measured by the ALSFRS-R questionnaire (total score >=30).
• have had symptoms of ALS (weakness) within 24 months of taking part in this trial.
• have not received treatment for ALS or are currently on a stable dose of an approved treatment for ALS.
• have the ability to slowly exhale a volume of air at least 60% of what is expected for the participant's sex, height and age.

Key Exclusion Criteria:

• Use of other investigational drugs within 5 half-lives of screening, or within 30 days (e.g., small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 24 weeks after stopping study medication.
• History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study.
• Clinical evidence of liver or renal disease/injury.
• Laboratory evidence of hematological abnormalities
• Presence of unstable psychiatric disease, cognitive impairment, neurological disease other than ALS, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the investigator's opinion.
• Participants that reported 'yes' on any suicidal ideation section except for the "Non-Suicidal Self-Injurious Behavior" in the past 2 years as per C-SSRS.
• Presence of cancer, HIV, Hep B, Hep C, tuberculosis, uncontrolled diabetes
• History of active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis.
• Taking any prohibited medications

Study Status: Active, recruiting.

Sponsor: Novartis Pharmaceuticals

Purpose of the Study: The purpose of this study is to evaluate safety, effect on cramps, function and quality of life of ranolazine versus placebo for the treatment of ALS.

Key Inclusion Criteria:

• 18 years or older
• Diagnosed with clinically definite, possible, probably, or lab-supported probable ALS per revised El Escorial criteria
• Breathing assessment called forced vital capacity (FVC) greater than or equal to 50%.\
• Able to swallow pills at the start of the study and expected to for the length of the study.
• If on ALS modifying medications must be on a stable dose at least 30 days.
• Experiencing 4 or more cramps per week during a 2-week screening period.

Key Exclusion Criteria:

• Disease duration < 5 years
• Tracheostomy invasive ventilation, or noninvasive ventilation of more than 12 hours/day
• Pregnant or lactating, adults unable to consent, and prisoners
• Taking ranolazine or investigational drug or has received an investigational drug within 30 days (or 5 half-lives for drugs, whichever is longer) prior to screening
• Medically uncontrolled comorbidities (heart, liver, kidney disease)
• Baseline QTc interval prolongation >450 ms for men/ >470 ms for women, history of long QT syndrome, or medications which prolong the QT interval
• Participation in an experimental drug trial less than 30 days before screening
• Patients have to be on a stable dosage of any medications used to treat muscle cramps for ≥30 days or have been off these medications ≥30 days prior to randomization.
• Presence of unstable psychiatric disease, cognitive impairment, neurological disease other than ALS, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the investigator's opinion.
• Participants that reported 'yes' on any suicidal ideation section except for the "Non-Suicidal Self-Injurious Behavior" in the past 2 years as per C-SSRS.
• Presence of cancer, HIV, Hep B, Hep C, tuberculosis, uncontrolled diabetes
• History of active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis.
• Taking any prohibited medications

Study Status: Active, recruiting.

Sponsor: Swathy Chandrashekhar, MD

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:

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.
2. 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).
3. 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.
4. 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
5. Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, assessments, and visits.
6. 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.
7. 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.

8. 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.
9. 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:

1. 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.
2. 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.

* 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

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

Exclusion Criteria for Part 1:

1. Requires permanent ventilation (> 22 hours of mechanical ventilation [invasive or noninvasive] per day for > 21 consecutive days) or tracheostomy
2. 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
3. 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
4. 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
5. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
6. Uncontrolled hypertension (BP > 160/100 mmHg)
7. 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.
8. Obstructive hydrocephalus
9. Presence of a functional ventriculoperitoneal shunt for the drainage of CSF or an implanted CNS catheter
10. 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
11. 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
12. Concurrent participation in any other interventional clinical study
13. 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.
14. 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
15. History of gene therapy or cell transplantation or any other experimental brain surgery
16. 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.
17. Clinically significant low platelet count (defined as < 100,000/mm3), coagulation tests, or laboratory abnormalities that would render a patient unsuitable for inclusion
18. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
19. 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.

Purpose of the Study: This is an open-label extension (OLE) study designed to evaluate the long-term safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical effects of subcutaneous (SC) administration of CTI-1601, also known as nomlabofusp, in subjects with Friedreich's ataxia (FRDA).

The objectives of this OLE study are:

• To evaluate the safety of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA
• To evaluate the PK of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA
• To evaluate the effect of long-term subcutaneous (SC) administration of CTI-1601 in subjects with FRDA on:
  
  • Tissue FXN concentrations
  • Clinical evaluations of FRDA
  • Gene Expression and select lipids

Key Exclusion Criteria:

• Subjects with FRDA who previously completed participation in a study of CTI-1601 will be eligible to participate in this study unless the subject experienced one or more of the following in a previous CTI-1601 study: a) serious adverse event (SAE) related to study drug; b) significant AE, defined as Grade 3 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (or higher), related to study drug; c) some other event, related to participation in a previous study with CTI-1601, that supports the exclusion of the subject from participating in this study as determined by the Sponsor (i.e., an AE considered clinically significant by the Sponsor regardless of whether it met SAE criteria and regardless of CTCAE grade); d) Withdraw from participation in a previous study of CTI-1601 for any reason.
• Subject has a HbA1c less than or equal to 7.0%.
• Subject must demonstrate sufficient dexterity and visual acuity to prepare and self-administer SC injections of CTI-1601 QD or is able to identify a caregiver who will be trained and committed to prepare and administer the daily injections.

Key Exclusion Criteria:

•  Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only one allele) for FRDA.
• Subject has any condition, disease, or situation, including a cardiac condition or disease, that in the opinion of the PI, could confound the results of the study or put the subject at undue risk, making participation inadvisable.
• Subject used any investigational drug (other than CTI-1601) or device within 90 days prior to Screening.
• Subject requires use of amiodarone.
• Subject used erythropoietin, etravirine, or gamma interferon within 90 days prior to Screening.
• Subject use of biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days prior to the first dose of study drug. Biotin supplementation ≤30 mcg/day is permitted if taken at a stable dose and frequency for at least 28 days prior to Screening and there is a commitment from the subject to maintain the biotin dose throughout the study (due to interference with assays).
• Subject uses more than 3 grams of acetaminophen daily.
• Subject receives medication that requires SC injection in the abdomen or thigh.
• Subject is unable to discontinue medications that have not been at a stable dose and frequency for at least 28 days prior to Screening.
• Subject has a Screening echocardiogram (ECHO) LVEF < 45%.
• Male subject has a QTcF > 450 milliseconds or female subject has a QTcF > 470 milliseconds on an ECG.

Study Status: Active, recruiting by Invitation

Sponsor: Larimar Therapeutics, Inc.

Purpose of the Study: This project is a global, multicenter, prospective, longitudinal, observational natural history study that can be used to understand the disease progression and support the development of safe and effective drugs and biological products for Friedreich ataxia.

Eligibility Criteria:

• Both males and females of any age
• Individuals with Friedreich ataxia (FA): Participants that meet genetically confirmed diagnosis of Friedreich ataxia
• Written informed consent provided
  • Informed consent must be obtained for all participants
  • For underage participants, they and the parent/ legally authorized representative have to sign the informed consent form, child assent (if applicable)
  • Persons who are not legally competent require the informed consent of their legally authorized representative

Key Exclusion Criteria:

• Unable or unwilling to provide informed consent
• Acute or ongoing medical or other conditions that would interfere with the conduct and assessments of the study
• For any reason in the opinion of the investigator, participant would be unlikely or unable to comply with study protocol requirements.

Study Status: Active, recruiting.

Sponsor: Friedreich's Ataxia Research Alliance

Purpose of the Study: Interventional: to evaluate the safety and tolerability of RTA-408 and the change in peak work in maximal exercise testing in individuals with Friedreich’s Ataxia

Eligibility Criteria:

• Genetically confirmed Friedreich’s ataxia
• Male or female, age 16-40 inclusive
• No changes to their exercise regimen within 30 days prior to study day 1 and willing to remain on the same exercise regimen during the study
• Ability to complete maximal bicycle testing
• Adequate kidney function
• Able to swallow capsules

Study Status: Recruiting participants

Principal Investigator: J. Chad Hoyle, MD

Contact: Amy Barlett, 614-366-9050, Amy.bartlett@osumc.edu

Funding: Reata Pharmaceuticals, Inc.

Purpose of the Study: The purpose of this Phase 3 study is to demonstrate the efficacy of DNTH103 as compared to placebo in participants with chronic inflammatory demyelinating polyneuropathy (CIDP).

Eligibility Criteria:

• Must have given written informed consent before any study-related activities are carried out.
• Weight range between 40 kilograms (kg) and 120 kg.
• Confirmed diagnosis of CIDP or possible CIDP. Participants must have either typical CIDP or one of the following variants: motor or multifocal CIDP. Diagnosis must be confirmed by the Independent CIDP Review Panel.
• CIDP Disease Activity Status (CDAS) score ≥ 3 at screening.
• Must be neurologically stable (ie, no relapses or other neurological events that could affect examinations).
• Must have an adjusted INCAT score between 2 and 9 inclusive.
• Must fulfill one of the following treatment conditions for CIDP:
• Currently treated with and responded to immunoglobulin (Ig) (intravenous immunoglobulin [IVIg] or subcutaneous immunoglobulin [SCIg]) alone or Ig (IVIg or SCIg) plus oral corticosteroids, or previously treated with and responded to, but either no longer have access to or are no longer being treated with, Ig (IVIg or SCIg) alone or Ig (IVIg or SCIg) plus oral corticosteroids.
  • Currently treated with and responded to oral corticosteroids alone or oral corticosteroids in combination with azathioprine or mycophenolate mofetil, or previously treated with and responded to, but no longer have access to, oral corticosteroids.
  • Refractory participants who have had failure (worsened) or an inadequate response (defined as no clinically meaningful improvement after treatment for a minimum of 12 weeks on Ig and/or oral corticosteroids) or are unable to tolerate these treatments due to side effects.
  • Treatment naïve with no history of prior treatment for CIDP.
• Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability.
• Female participants must be of nonchildbearing potential or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception.
• Male participants must be surgically sterile for at least 90 days prior to Screening or agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception.

Key Exclusion Criteria:

•  Clinical signs or symptoms suggestive of polyneuropathy of other causes, such as inflammatory neuropathies.
• Known evidence of central demyelination or known history of myelopathy.
• History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant or that could have a potential impact on safety/efficacy or study procedures.
• Any other condition, including mental illness or prior therapy that would make the participant unsuitable for this study.
• Known complement deficiency or history of positive titer for anti-C1 antibodies.
• Diagnosis of systemic lupus erythematosus (SLE) or family history of SLE (defined as a parent, sibling, or child).
• Diagnosis of an autoimmune disorder other than CIDP.
• Any coexisting or overlapping condition, which may interfere with outcome assessments, such as severe diabetic neuropathy, fibromyalgia, inflammatory arthritis or osteoarthritis affecting the hands and feet.
• Prior history of N. meningitidis infection.
• History of active malignancy within 5 years prior to screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone.
• Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies.

Study Status: Active, recruiting

Funding: Dianthus Therapeutics

Purpose of the Study: The primary goal of this proposal is to collect motor and functional outcomes specific to FSHD over time. By collecting measures specific to FSHD, this will help ensure the best level of clinical care is being provided. Also, the hope is to speed up drug development by gaining a better understanding of how having FSHD impacts motor function and other health outcomes (i.e. breathing, wheelchair use, etc.) and how big a change in motor function would be clinically meaningful to those with FSHD.

Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) will have approximately 450 FSHD participants followed for a minimum of 3 years. A subset of MOVE FSHD participants, approximately 200, will participate in the MOVE+ sub-study which includes whole body MRI and reachable workspace, as well as optional muscle biopsy and wearable device (US participants only).

Key Inclusion Criteria:

• Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring.

Key Exclusion Criteria:

• Unwilling or unable to provide informed consent.
• Any other medical condition which in the opinion of the investigator would interfere with study participation.

Study Status: Active, recruiting

Sponsor: University of Kansas Medical Center

Purpose of the Study: The primary cause of facioscapulohumeral muscular dystrophy (FSHD), a common adult-onset dystrophy, was recently discovered identifying targets for therapy. As multiple drug companies pursue treatments for FSHD, there is an urgent need to define the clinical trial strategies which will hasten drug development, including creating disease-relevant outcome measures and optimizing inclusion criteria. This proposal will develop two new outcome measures and optimize eligibility criteria by testing 160 patients in 7 sites over a period of 18 months.

Key Inclusion Criteria:

• Patients with genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring
• Patients with symptomatic limb weakness
• Patients must be able to walk 30 feet without the support of another person or assistance (canes, walking sticks, and braces allowed; no walker).
• If taking over the counter supplements, willing to remain consistent with supplement regimen throughout the course of the study

Key Exclusion Criteria:

• Patients with cardiac or respiratory dysfunction (deemed clinically unstable, or would interfere with safe testing, in the opinion of the Investigator)
• Patients with orthopedic conditions that preclude safe testing of muscle function
• Patients that regularly use available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists
• Patients that have used an experimental drug in an FSHD clinical trial within the past 30 days
• Patients that are pregnant

Study Status: Active, not recruiting.

Sponsor: University of Kansas Medical Center

Purpose of the study: A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous AOC 1020 for the Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD)

Key inclusion criteria

• Clinical and genetic diagnosis of FSHD1 or FSHD2
• Ability to walk independently at pre-specified walking speed (orthoses and ankle braces allowed) for at least 10 meters at screening
• Adequate muscle strength based on QMT composite score

Key exclusion criteria

• Breastfeeding, pregnancy, or intent to become pregnant during the study
• Unwilling or unable to comply with contraceptive requirements
• Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
• Blood Pressure > 140/90 mmHg at Screening
• Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of the drug, whichever is longer
• Treatment with an oligonucleotide within 9 months of Screening

Study status: Active, recruiting.

Sponsor: Avidity Biosciences, Inc.

Contact email: nmresearch@osumc.edu

Purpose of the Study: The purpose of this Phase 2 study is to evaluate the safety, tolerability, pharmacometrics, and efficacy of DNTH103 in participants with multifocal motor neuropathy(MMN).

Key Inclusion Criteria:

• Must have given written informed consent before any study-related activities are carried out
• Adult males and females, 18 to 75 years of age (inclusive)
• Weight range between 40 to 120 kg
• Confirmed diagnosis of definite or probable MMN
• Evidence of:
  • Responsiveness to Ig treatment; and
  • Receiving a stable Ig regimen
• Documented vaccinations against encapsulated bacteria in accordance with local requirements and vaccine availability
• Female participants must be of nonchildbearing potential or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception
• Male participants must be surgically sterile for at least 90 days prior to Screening or agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception 

Key Exclusion Criteria:

• History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant or that could impact efficacy assessments
• Any coexisting conditions which may interfere with outcome assessments (eg, severe diabetic neuropathy)
• Concurrent or previous use of rituximab, cyclophosphamide, mycophenolate mofetil, azathioprine, or cyclosporine. If a participant has previously used these medications, the last dose must be at least 6 months prior to randomization
• Currently or previously on complement inhibitors including in a clinical trial setting
• Prior history (at any time) of N. meningitidis infection
• Diagnosis of an autoimmune disorder other than MMN
• Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies during Screening
• History of active malignancy within 5 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone
• Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent (whichever is longer) prior to randomization (Day 1)
• Any other overlapping condition for which the condition or treatment of the condition may affect the study assessments or outcomes
• Any other condition, including mental illness or prior therapy, that in the opinion of the Investigator would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements

Study Status: Active, recruiting

Sponsor: Dianthus Therapeutics

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

Purpose of the Study: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Global Study to Evaluate the Efficacy and Safety of Intravenous Delpacibart Etedesiran (abbreviated del-desiran, formerly AOC 1001) for the Treatment of Myotonic Dystrophy Type 1

Key Inclusion Criteria:

• Clinical and genetic diagnosis (CTG repeat ≥ 100) of DM1
• Ability to walk independently (orthoses and ankle braces allowed) for at least 10 meters at screening

Key Exclusion Criteria:

• Breastfeeding, pregnancy, or intent to become pregnant during the study
• Unwilling or unable to comply with contraceptive requirements
• Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
• Diabetes that is not adequately controlled
• History of decompensated heart failure within 3 months of screening. Participants with preexisting pacemaker/ICD are not excluded.
• Body Mass Index > 35 kg/m2 at Screening
• Recently treated with an investigational drug or biological agent
• Treatment with anti-myotonic medication within 5 half-lives or 14 days of baseline, whichever is longer, prior to baseline.

Study Status: Active, recruiting.

Sponsor: Avidity Biosciences, Inc.

Purpose of the study: A Global Phase 3 Open-Label Extension Study to Assess the Long-Term Safety, Tolerability, and Efficacy of Intravenous Delpacibart Etedesiran (abbreviated del-desiran, formerly AOC 1001) for the Treatment of Myotonic Dystrophy Type 1

Key inclusion criteria

• Completion of any prior AOC 1001 studies with satisfactory completion of dosing and follow-up assessments and satisfactory compliance with the protocol requirements of the parent study, as determined by the Investigator.

Key exclusion criteria

• Breastfeeding, pregnancy, or intent to become pregnant during the study.
  Unwilling to comply with contraceptive requirements.
  Any new conditions or worsening of existing condition that in the opinion of the Investigator would make the participant unsuitable for the study.

Study status: Active, recruiting.

Sponsor: Avidity Biosciences, Inc.

Contact email: nmresearch@osumc.edu

Purpose of the Study: This is an observational study to investigate the improvement of NMJ defects in adult patients with SMA following treatment with Risdiplam. Eligible patients will have received treatment with daily oral Risdiplam after receiving approval through their commercial insurance or drug assistance program. All subjects will be evaluated at one visit. Eligible subjects must have been receiving risdiplam for at least 12 months.

Key Inclusion Criteria:

• Signed Informed Consent Form
• Age 18-70 years at time of signing Informed Consent Form
• Able and willing to provide written informed consent and to comply with the program protocol according to ICH and local regulations
• Ability to comply with the study protocol, in the investigator's judgment
• Adequately recovered from any acute illness at the time of screening, and considered clinically well enough to participate, in the opinion of the treating physician
• Patients with retinopathy of prematurity should have evidence of stable disease
• Genetic confirmation of 5q SMA documented on standard genetic tests for the disorder
• Treated with risdiplam for a duration of 12 months or longer

Key Exclusion Criteria:

• Treatment with an investigational therapy within 180 days prior to initiation of study drug
• History of established diagnosis of neuromuscular junction disorder
• Co-morbid conditions that preclude travel or testing
• Patients who are, in the investigator's opinion, mentally or legally incapacitated to provide an informed consent

Study Status: Active, recruiting

Sponsor: Bakri Elsheikh

Purpose of the study: The purpose of this expanded access program (EAP) is to provide access to apitegromab for eligible patients with spinal muscular atrophy (SMA) prior to approval by the local regulatory agency . A medical doctor must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.

Key inclusion criteria:

• ≥2 years of age.
• Documented diagnosis of 5q SMA.

Key exclusion criteria:

• Previous history of a hypersensitivity reaction to a monoclonal antibody or recombinant protein bearing an Fc domain (eg, a soluble receptor-Fc fusion protein), apitegromab, or excipients of apitegromab.
• Enrolled in a clinical study for any investigational drug.
• Pregnant or breastfeeding.

Study status: Active, recruiting

Sponsor: Scholar Rock, Inc.

Contact email: nmresearch@osumc.edu

Purpose of the Study: The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in patients with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran or the reference comparator patisiran during the Treatment Period. The Treatment Period is followed by a Treatment Extension Period during which all participants in the patisiran group will switch to vutrisiran. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints.

Key Inclusion Criteria:

• Male or female of 18 to 85 years of age (inclusive);
• Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation;
• Has adequate neurologic impairment score (NIS);
• Has adequate polyneuropathy disability (PND) score;
• Has adequate Karnofsky Performance Status (KPS).

Key Exclusion Criteria:

• Had a prior liver transplant or is likely to undergo liver transplantation during the study;
• Has known other (non-hATTR) forms of amyloidosis or leptomeningeal amyloidosis;
• Has New York Heart Association heart failure classification >2;
• Clinically significant liver function test abnormalities;
• Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
• Received an experimental drug within 30 days of dosing;
• Received prior TTR-lowering treatment;
• Has other known causes of neuropathy.

Study Status: Active, not recruiting.

Sponsor: Alnylam Pharmaceuticals

Purpose of the Study: The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.

Key Inclusion Criteria:

• Adult patients with generalized Myasthenia Gravis (age 18-75 years)
• Positive serology testing for AChR+ antibody at screening
• Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG and likely not in need v of a respirator for the duration of the study, as judged by the Investigator.
• The confirmation of the diagnosis of gMG should be documented and supported by ≥1 of the following 3 tests:
• History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation.
• History of positive edrophonium chloride test
• Patient has demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician.
• Baseline MG-ADL score ≥6, with ≥50% of the total score due to non-ocular symptoms
• Participants not optimally controlled for ≥ 6 months on
• just one NSIST; or
• two or more NSISTs; or
• on frequent (at least quarterly) plasmapheresis, plasma exchange, or intravenous immunoglobulin to control symptoms despite treatment with steroids and NSISTs; or
• one of the following gMG treatments:
• a FcRN antagonist approved for gMG
• rituximab
• other approved gMG therapies excluding complement inhibitors.
• Consistent with all other iptacopan trials, participants will have to be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae. In addition, participants will be vaccinated against Haemophilus influenzae, depending on the local regulations and on the availability of this vaccine in the countries of study conduct. The vaccination will be performed at least 2 weeks prior to first dosing with iptacopan, covering as many serotypes as possible. If iptacopan treatment will start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment must be initiated and administered until 2 weeks post vaccination.

Key Exclusion Criteria:

• Have been treated with intravenous immunoglobulin (IVIG)/plasma exchange (PLEX) in the past month, with rituximab in the past 6 months, eculizumab in the past 2 months, ravulizumab or other complement inhibitors in the past 3 months, efgartigimod or other anti- FcRn therapies in the past 3 months, or had a thymectomy in the past 6 months or a planned thymectomy during the trial period.
• Participants with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV): serologic panel test results indicative of an active (acute or chronic) infection; Active Hepatitis C Virus (HCV): serology positive for HCV-Ab; Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count
  • 200 cells/mm3
• Female participants who are pregnant or lactating, or are intending to become pregnant.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
• Active systemic bacterial, viral (including COVID-19) or fungal infection or any major episode of infection that required hospitalization or injectable antimicrobial therapy within 14 days prior to study drug administration.
• History of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae.
• Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration

Study Status: Active, recruiting

Sponsor: Novartis Pharmaceuticals

Purpose of the Study: Phase 1b/2a First-in-Human (FIH) clinical trial to assess the safety, tolerability, pharmacodynamics (PD), and efficacy of multiple ascending doses of CNP-106.

Key Inclusion Criteria:

• Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations.
• Men and non-pregnant women, ages 18-75 years inclusive.
• Female subjects of childbearing potential must agree not to become pregnant during the clinical study, have a negative pregnancy test at the Screening Visit, and agree to one of the following:
  • Use two highly effective forms of birth control starting at initial screening and continuing throughout the study duration.
  • Practice abstinence starting at initial screening and continuing throughout the study duration.
• Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class III-IV (Cohort 1). Upon successful DMC review and approval of preliminary safety data obtained from Cohort 1 through Day 15, Cohort 2 will enroll subjects with MGFA Clinical Classification Class II-IV.
• Subjects positive for anti-AChR antibodies by radioimmunoassay (RIA) (Mayo Clinic).
• Subjects with MG-ADL Score ≥ 6 at Screening and Baseline Visit with ≥ 50% of the score derived from non-ocular symptoms.
• Subjects with QMG Score ≥ 11 at Screening and Baseline Visit.
• For subjects on any medication used to treat the symptoms of MG (ex. Corticosteroids, pyridostigmine), subjects must be on a stable dose for a minimum of 90 days prior to enrollment and must agree not to increase their dose through clinical study duration unless reviewed and approved by the medical monitor and the site investigator.
• Female subjects who agree to not breastfeed starting at initial screening and throughout the study duration.
• Female subjects who agree to not donate ova starting at initial screening and throughout the study duration.
• Male subjects with a spouse or partner of childbearing potential, who themselves and their spouse or partner agree to practice an effective form of birth control as discussed with the study doctor or study staff starting at Screening and throughout the study duration.

Key Exclusion Criteria:

• Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class I or V.
• Subjects with a history of cerebrovascular accident in the past 12 months.
• Subjects with MG-ADL Score < 6 at Screen or Subjects with MG-ADL Score ≥ 6 at Screen with ˂ 50% of the score derived from non-ocular symptoms.
• Subjects with QMG Score < 11 at Screen.
• Subjects who have used the following medications:
  • Tacrolimus within 6 months prior to the first dosing;
  • Methotrexate within 5 half-lives or 90 days after last dose (whichever is longer);
  • Anti-FcRn inhibitors (ex. Efgartigimod) within 5 half-lives or 90 days after last dose (whichever is longer);
  • C5 complement inhibitor (ex. Eculizumab) within 5 half-lives or 90 days after last dose (whichever is longer);
  • Anti-CD20 (ex. Rituximab) within 5 half-lives for 90 days after last dose (whichever is longer);
  • Inclusion of subjects on other immunomodulatory drugs will be at the discretion of the medical monitor and study site investigator.
• Subjects who have used immunoglobulins given SC or IV (SCIg or IVIg) or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening.
• Subjects who have had thymectomy or any other thymic surgery performed within 12 months prior to Screening.
• Subjects with untreated thymic malignancy, carcinoma, or thymoma.
• Subjects with a history of tuberculosis or positive PPD skin test.
• Subjects who have received administration of any live vaccine (other than intranasal Influenza) within 28 days or subunit vaccine within 14 days prior to Screening or are planning to receive any vaccination throughout the study duration.
• Subjects who have received any COVID-19 vaccine within 14 days prior to Screening. Subjects who have received the first dose of any COVID-19 vaccine may not screen for the study until 14 days following their last dose of the vaccine if applicable.
• Subjects with laboratory test results at Screening or prior to study dosing that are outside the normal limits and considered by the investigator to be clinically significant. Note: Clinically significant laboratory test results at screening that are related to the condition (MG) are acceptable as long as all inclusion and no other exclusion criteria are met.
• Subjects with positive test results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/antibody as determined at Screening.
• Subjects with a history of or currently active immune disorders other than MG (including autoimmune disease) unless the condition, after discussion with the medical monitor and study site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
• Subjects with a history of or current active diseases other than myasthenia gravis requiring immunosuppressive drugs (including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil) unless the condition, after discussion with the medical monitor and site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
• Subjects with a clinical history of significant cardiovascular disease as determined by the Investigator.
• Subjects with a complication or medical history of malignancy within the past 5 years which, in the investigator's opinion, makes the subject unsuitable for study participation.
• Subjects with a history of mast cell activation disease.
• Subjects who, in the investigator's opinion, will be unable to adhere to study procedures.
• Subjects who have received an investigational therapy other than CNP-106 within 28 days or 5 half-lives, whichever is longer, prior to Screening.
• Subjects with any known active condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
• Known sensitivity to any components of CNP-106 (PLGA, sucrose, mannitol or sodium citrate).

 Study Status: Active, recruiting

Sponsor: COUR Pharmaceutical Development Company, Inc.

Purpose of the Study:

• Describe epidemiological and clinical characteristics, natural history and real-world clinical management of ATTR amyloidosis patients
• Characterize the safety and effectiveness of patisiran and vutrisiran as part of routine clinical practice in the real-world clinical setting
• Describe disease emergence/progression in pre-symptomatic carriers of a known disease-causing transthyretin (TTR) variant

Key Inclusion Criteria:

• Diagnosis of ATTR amyloidosis or documented known disease-causing TTR variant for the cohort of pre-symptomatic carriers
• Germany Only: Patients must be treated per the summary of product characteristics (SmPC) for any approved treatment for ATTR amyloidosis

Key Exclusion Criteria:

• Current enrollment in a clinical trial for any investigational agent

Study Status: Active, recruiting.

Sponsor: Alnylam Pharmaceuticals