Movement Disorders Clinical Trials

Purpose of the Study: 

A Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH. The study consists of 3 periods: (i) 4-week screening, (ii) 4-week randomized treatment, and (iii) 2-week follow up. The trial utilizes an operational design featuring the ability to conduct protocol required visits as either in clinic or remote visits (except Screening visit).

Eligibility Criteria:

• Subject is male or female and at least 30 years old.
• Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a sustained reduction in BP of ≥20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3 minutes of being tilted-up to ≥60o from a supine position as determined by a tilt-table test.
• Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit.
• For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992).
• For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
• For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization.
• Subject has plasma NE levels >100 pg/mL after being in seated position for 30 minutes.

Exclusion Criteria

• Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies.
• Subject has a known intolerance to other NRIs or SNRIs.
• Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
• Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization or requires concomitant use until the follow-up visit.
• Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1.
  Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1.
• Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
• Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
• Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
• Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject.
• Subject has any significant uncontrolled cardiac arrhythmia.
• Subject has a Montreal Cognitive Assessment (MoCA) ≤23.
• Subject had a myocardial infarction in the past 6 months or has current unstable angina.
• Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
• Subject has a clinically significant abnormal laboratory findings (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3.0 x upper limit of normal [ULN]; blood bilirubin [total] >1.5 x ULN; estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2, or any abnormal laboratory value that could interfere with safety of the subject).
• Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale) (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.

 

Status: Recruiting.

Sponsor: Theravance Biopharma

 

Purpose of the Study: 

This study is designed to evaluate the safety and efficacy of dipraglurant in PD patients with dyskinesia (randomized 1:1 to receive active or placebo) for 12 weeks (1 week at 150 mg per day and 11 weeks at 300 mg per day). The primary efficacy assessment will be based on the Unified Dyskinesia Rating Scale (UDysRS). Patients who complete the 12-week blinded treatment period may have the option to roll into an open-label safety extension study for an additional 12-month treatment period.

Eligibility Criteria:

• Patients with Parkinson's Disease on a stable regimen of antiparkinson's medications, including a levodopa preparation administered not less than 3 times daily.
• Meet protocol-specified criteria for moderate to severe dyskinesia symptoms based on UDysRS and Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assessments.
• Meet protocol specified criteria for ON time with troublesome dyskinesia based on a standard PD home diary.

Exclusion Criteria

• Prior surgical treatment for Parkinson's Disease (e.g., deep brain stimulation).
• Other neurological disease (including psychiatric disease and/or cognitive impairment) that, in the opinion of the investigator, would affect the patient's ability to complete study assessments.
• Other significant medical condition that may affect the safety of the patient or preclude adequate participation in the study.
• Pregnant or breast-feeding. Female patients who are of child-bearing potential must be using adequate contraceptive methods (e.g. oral contraceptive, double-barrier method, intra-uterine device, intra-muscular hormonal contraceptive), and have a negative pregnancy test at Screening.

 

Status: Not yet recruiting.

Sponsor: Addex Pharma S.A.

 

Purpose of the Study: 

 This is a phase 2 study designed to assess the safety, tolerability and efficacy of NLY01 in subjects with early untreated Parkinson's disease (PD). Evidence suggests NLY01, a pegylated form of exenatide, may be beneficial in PD and is being developed as a potential treatment for neurodegenerative disorders.

Eligibility Criteria:

• Patients who are diagnosed with Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Clinical Diagnostic criteria or Movement Disorder Society Research Criteria
• Patients with Parkinson's disease according to protocol specified scale assessments
• DaTscan consistent with diagnosis of Parkinson's Disease
• Men or women 30 to 80 years of age

Exclusion Criteria

• Diagnosis of secondary or atypical parkinsonism
• Prior use of dopaminergic treatment or MAO-B inhibitors for more than 28 days
• Medical or recreational use of marijuana or THC-containing compounds within 3 months of screening visit
• Pregnant or planning to become pregnant
• Metabolic, surgical, psychiatric or laboratory abnormality that would interfere with study compliance or safety in the judgment of the investigator

Link:

https://prismpdstudy.com/

Sponsor:

Neuraly, Inc.

 

Purpose of the Study: 

Parkinson's disease (PD) is a neurological condition, which affects the brain. PD gets worse over time, but how quickly it progresses varies a lot from person to person. Some symptoms of PD are tremors, stiffness, and slowness of movement. This study measures the efficacy, safety, and tolerability of ABBV-951 versus oral Levodopa (LD)/Carbidopa (CD) [LD/CD] in advanced PD participants to achieve reduction in motor fluctuations. 

Eligibility Criteria:

• Diagnosis of idiopathic Parkinson's Disease (PD) that is levodopa-responsive.
• Participants must be taking a minimum of 400 milligrams/day (mg/day) of Levodopa (LD) equivalents and be judged by the investigator to have motor symptoms inadequately controlled by current therapy, have a recognizable/identifiable "Off" and "On" states (motor fluctuations), and have an average "Off" time of at least 2.5 hours/day over 3 consecutive PD Diary days with a minimum of 2 hours each day.
• Participant or caregiver, if applicable, demonstrates the understanding and correct use of the delivery system, including the insertion of the cannula into the participant's abdomen, as assessed by the investigator or designee during the Screening period.

Exclusion Criteria

• Clinically significant, unstable medical conditions or any other reason that the investigator determines would interfere with the participant's participation in this study or would make the participant an unsuitable candidate to receive study drug.
• History of allergic reaction or significant sensitivity to LD or constituents of the study drug (and its excipients) and/or other products in the same class.
• Has no known active Coronavirus Disease - 2019 (COVID-19) infection.

Link:

https://clinicaltrials.gov/ct2/show/NCT04380142?term=M15-736&draw=2&rank=1

Sponsor:

AbbVie

 

Official Title:

A Randomized, Placebo Surgery Controlled, Double-blinded, Multi-center, Phase 2 Clinical Trial, Evaluating the Efficacy and Safety of VY-AADC02 in Advanced Parkinson's Disease With Motor Fluctuations

Purpose of the Study: 

 The main purpose of this study is to test the safety and efficacy (how well it works) of an experimental intervention called VY-AADC02 on the severity of Parkinson’s Disease (PD).

Eligibility Criteria:

You may be eligible if you:
1. Are between the ages of 40 to 75 years of age
2. Have been diagnosed with PD for at least 4 years
3. Are on a stable regimen of Parkinson's medications for at least 4 weeks prior to screening evaluation
4. Have the ability to travel to study visits

Key Exclusion Criteria:

1. Atypical or secondary parkinsonism, including but not limited to symptoms believed to be due to trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals, or toxins
2. Use of tetrahydrocannabinol within 6 months of screening evaluation
3. History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation.

Contact:
Katherine Ambrogi, BSN, RN
Phone: 614-688-6685
Email: katherine.ambrogi@osumc.edu

Purpose of the Study: 

The purpose of this international study is to evaluate long-term safety and effectiveness of Abbott deep brain stimulation (DBS) systems for all indications, including Parkinson's disease, essential tremor and dystonia. 

Eligibility Criteria:

1. Subject is scheduled for a new implant or implantable pulse generator (IPG) device replacement surgery with a market-released Abbott DBS system within 3 months.
2. Subject, or a legally acceptable representative, must provide written informed consent prior to any clinical investigation-related procedure.

Exclusion Criteria

1. Subject is currently enrolled or plans to enroll in another concurrent study that may confound the results of this clinical investigation, as determined by Abbott.
2. Subject has anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.

Contact:

Barbara Changizi, MD

Phone: 614-366-2420

Link:

https://clinicaltrials.gov/ct2/show/NCT04071847?term=ADROIT+study&draw=2&rank=1

Sponsor:

Abbott Medical Devices

Purpose of the Study: 

The purpose of this registry is to compile characteristics of world-wide outcomes for the use of Boston Scientific's commercially available Vercise DBS system in the treatment of Parkinson's disease.

Additionally, the utilization of Guide XT (GXT) System when used as a planning tool for the programming of patients with the Boston Scientific's Vercise DBS Systems is also evaluated.

Eligibility Criteria:

• Meets criteria established in locally applicable Vercise System Direction for Use
• At least 18 years old

Exclusion Criteria

• Meets any contraindication in the Vercise System locally applicable Directions for Use

Contact:

BSNClinicalTrials@bsci.com

Link:

https://clinicaltrials.gov/ct2/show/NCT02071134?term=US+DBS+Registry&draw=2&rank=2

Sponsor:

Boston Scientific Corporation

Purpose of the Study: 

The purpose of this study is to evaluate the clinical efficacy, safety and pharmacokinetics (PK) of 2 fixed doses of tavapadon and placebo in participants with early PD.

Eligibility Criteria:

• Male and female participants aged 40 to 80 years, inclusive, at the time of signing the ICF (Informed consent form).
• Participants with a diagnosis of that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria, with bradykinesia and motor asymmetry
• Participants with modified Hoehn and Yahr stage 1, 1.5, or 2
• Participants with disease duration (from time of diagnosis) of less than (<) 3 years and disease progression in the 3 years before signing the informed consent form (ICF)
• Participants with an MDS-UPDRS Part II score greater than or equal to (>=)2 and Part III score >=10 at the screening visit
• Participants with early PD who, in the opinion of the investigator, require pharmacologic intervention for disease management
• Participants who are treatment naïve or have a history of prior incidental treatment with dopaminergic agents (including L-Dopa and dopamine receptor agonist medications) for <3 months and not within 2 months of signing the ICF. Prior and concurrent use of Monoamine oxidase (MAO)-B inhibitors is permitted if use was initiated > 90 days before signing of the ICF and the dosage will remain stable for the duration of the trial (i.e, no change in the MAO-B inhibitor dose is permitted during the trial)
• Participants who are willing and able to refrain from any PD medications that are not permitted by the protocol (including dopaminergic agents) throughout participation in the trial

Exclusion Criteria

• Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supra nuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or post stroke parkinsonism)
• Participants with a history of nonresponse or insufficient response to L-Dopa or 2 or more other antiparkinsonian drugs at therapeutic dosages
• Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5)
• Participants with the presence of or history of brain tumor, hospitalization for severe head trauma, epilepsy (as defined by the International League Against Epilepsy), or seizures
• Participants with a history of psychosis or hallucinations within the previous 12 months based on medical records or participant/caregiver feedback
• Participants who answer "yes" on the C-SSRS Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR Participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide.
• Participants with substance abuse or dependence disorder, including alcohol, benzodiazepines, and opioids, but excluding nicotine, within the past 6 months (180 days)
• Participants with dementia or cognitive impairment that, in the judgement of the investigator, would exclude the participant from understanding the ICF or participating in the trial
• Participants with any condition that could possibly affect drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding)
• Participants with a history of neuroleptic malignant syndrome
• Participants who are currently receiving moderate or strong CYP3A4 inducers or CYP3A4 inhibitors (except for topical administration)
• Participants with a positive urine drug screen for illicit drugs are excluded and may not be retested or rescreened. Participants with a positive urine drug screen resulting from use of marijuana (any Tetrahydrocannabinol [THC]-containing product), prescription, or over-the-counter medications or products that, in the investigator's documented opinion, do not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results may continue evaluation for the trial following consultation and approval by the medical monitor
• Participants with a Montreal Cognitive Assessment (MoCA) score <26.

Contact:

Ariane Park, MD, MPH

Phone: 614-293-4649   Email: ariane.park@osumc.edu

Link:

https://clinicaltrials.gov/ct2/show/NCT04201093?term=CVL-751-PD-001&draw=2&rank=1

Sponsor:

Cerevel Therapeutics, LLC

 

Purpose of the Study: 

The purpose of this study is to assess the effect of tavapadon on the change from baseline in total daily hours of "on" time without troublesome dyskinesia in L-Dopa-treated participants with Parkinson's Disease (PD) who are experiencing motor fluctuations.

Eligibility Criteria:

• Sexually active men or women of childbearing potential must agree to practice effective birth control, or remain abstinent during the trial and for 4 weeks after the last dose of trial treatment
• Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Participants who are able, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures
• Participants with a diagnosis of PD that is consistent with the UK Parkinson's Disease Society Brain Bank diagnostic criteria, with bradykinesia and motor asymmetry
• Participants with modified Hoehn and Yahr stage 2, 2.5, or 3 in the "on" state
• Participants with a good response to L-Dopa in the judgment of the investigator
• Participants who return a completed self-reported home diary for motor function status (Hauser diary) during the screening period (after diary training and concordance testing has occurred), with recordings for 2 consecutive days (ie, 2 consecutive 24-hour periods) showing at least 2 and half hours of "off" time on each of the 2 days
• Participants who are on a stable dose of L-Dopa for at least 4 weeks prior to screening and are taking a minimum total daily dose of 400 milligram (mg) divided in at least 4 doses per day of standard carbidopa/levodopa or divided in at least 3 doses per day of extended-release carbidopa/levodopa capsules. The carbidopa/levodopa dose and frequency must be maintained for the duration of the trial
• Prior and concurrent use of catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase (MAO-B) inhibitors, amantadine, or anticholinergic drugs is permitted if use was initiated greater than (>) 90 days before signing of the informed consent, the dosage has remained stable for a minimum of 4 weeks before signing of the informed consent, and the dosage will remain stable for the duration of the trial (ie, no change in the COMT, MAO-B inhibitor, or amantadine dose is permitted during the trial).

Exclusion Criteria

• Participants with a history or clinical features consistent with essential tremor, atypical or secondary parkinsonian syndrome (including, but not limited to, progressive supranuclear palsy, multiple system atrophy, cortico-basal degeneration, or drug-induced or poststroke parkinsonism)
• Participants with a history of nonresponse or insufficient response to L-Dopa at therapeutic dosages
• Participants who have had previous surgical intervention (eg, deep brain stimulation) for PD or for whom such a procedure is planned or anticipated during the trial period
• Participants with an acute or chronic, clinically significant medical or psychiatric condition, cognitive impairment, or laboratory abnormality that might increase the risk associated with trial participation or administration of trial treatment or interfere with the interpretation of the trial results or that, in the judgment of the investigator, would make the Participant inappropriate for entry into this trial.- Medical conditions that are minor or well controlled may be considered acceptable if the condition does not expose the Participant to an undue risk of a significant AE or interfere with the assessments of safety or efficacy during the course of the trial. Participants with symptoms of anxiety or depression that are not debilitating and that are stable or adequately controlled with non-prohibited medication are considered acceptable. The medical monitor should be contacted in any instance where the investigator is uncertain regarding the stability of a Participant's medical conditions(s) and the potential impact of the condition(s) on trial participation
• Participants with a history or current diagnosis of a clinically significant impulse control disorder (Disruptive, Impulse Control, and Conduct Disorder per DSM-5) (American Psychiatric Association, 2013)
• Participants with the presence of or history of brain tumor, hospitalization for severe head trauma, epilepsy (as defined by the International League Against Epilepsy), or seizures
• Participants with a history of psychosis or hallucinations within the previous 12 months
• Participants who answer "yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred within the last 6 months, OR Participants who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR Participants who, in the opinion of the investigator, present a serious risk of suicide
• Participants with substance abuse or dependence disorder, including alcohol, benzodiazepines, and opioids, but excluding nicotine, within the past 6 months (180 days)
• Participants with dementia or cognitive impairment that, in the judgement of the investigator, would exclude the Participant from understanding the ICF or participating in the trial
• Participants with any condition that could possibly affect drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding)
• Participants who have a positive result for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV) antibodies at screening
• Participants with a history of malignancy other than:
• Non-metastatic basal or squamous cell carcinoma of the skin or carcinoma in situ that was surgically removed in total >1 year before signing the ICF and had not recurred
• Another type of malignancy that had been in remission for ≥5 years before signing the ICF and had not recurred
• Participants with a history of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical intervention; second- or third-degree atrioventricular block; sick sinus syndrome; severe or unstable angina; or congestive heart failure within the last 12 months. A recent (less than or equal to [<=12] months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control
• Participants with a history of neuroleptic malignant syndrome
• Female Participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving IMP
• Participants who are currently receiving moderate or strong cytochrome P450 (CYP) 3A4 inducers or CYP3A4 inhibitors (except for topical administration)
• Participants with a positive urine drug screen for illicit drugs are excluded and may not be retested or rescreened. Participants with a positive urine drug screen resulting from use of marijuana (any tetrahydrocannabinol-containing product), prescription, or over-the-counter medications or products that, in the investigator's documented opinion, do not signal a clinical condition that would impact the safety of the Participant or interpretation of the trial results may continue evaluation for the trial following consultation and approval by the medical monitor
• Participants who are using any prohibited medication during the trial within at least 4 weeks or 5 half-lives (whichever is greater) prior to signing the ICF
• Participants with a Montreal Cognitive Assessment (MoCA) score <26
• Participants with a sitting blood pressure greater than or equal to (>=) 160 millimeter of Hg (mmHg) (systolic) or >=100 mmHg (diastolic) on a single measurement. If abnormal, up to 2 repeat measurements are permitted after at least 5 minutes of rest
• Participants with clinically significant orthostatic hypotension (eg, syncope)
• Participants with a 12-lead ECG demonstrating a QTcF interval >450 msec (average of 3 ECGs obtained at the Screening Visit)
• Participants with moderate or severe renal impairment (creatinine clearance as estimated by Cockcroft-Gault formula <30 milliliter per minute [mL/min] or on dialysis)
• Participants with any of the following abnormalities in clinical laboratory tests at the Screening Visit, as assessed by the central laboratory and confirmed by a single repeat measurement, if deemed necessary:
• AST or ALT >=3 × Upper Limit Normal (ULN)
• Total bilirubin >=1.5 × ULN. Participants with a history of Gilbert's syndrome may be eligible provided they have a value <ULN for direct bilirubin
• Participants with other abnormal laboratory test results, vital sign results, or ECG findings unless, in the judgment of the investigator, the findings are not medically significant and would not impact the safety of the Participants or the interpretation of the trial results. The medical monitor should be contacted to discuss individual cases, as needed. Tests with exclusionary results should be repeated to ensure reproducibility of the abnormality before excluding a Participant based on the criteria provided in the protocol. For ECGs, 3 consecutive recordings are required and if 2 of the 3 remain exclusionary, then the Participant is not eligible for the trial
• Participants who previously participated in any tavapadon trial, including this trial, and received investigational medicinal product (IMP)
• Participants who received treatment with any other investigational drug within 60 days before signing the ICF
• Any Participant who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial.

Contact:

Ariane Park, MD, MPH

Phone: 614-293-4649   Email: ariane.park@osumc.edu

Link:

https://clinicaltrials.gov/ct2/show/NCT04542499?term=CVL-751-PD-003&draw=2&rank=1

Sponsor:

Cerevel Therapeutics, LLC

 

Purpose of the Study: 

The objective of this Phase 1b investigation is to evaluate the safety and potential clinical effect of AAV2-GDNF delivered to the putamen in subjects with either a recent or a long-standing diagnosis of PD. 

Eligibility Criteria:

• Male and female adults 35-75 years of age (inclusive)
• Diagnosed with Parkinson's disease
• Modified Hoehn and Yahr stage I-III OFF medication

• Time since receiving a clinical diagnosis of PD and disease severity consistent with one of the following:

  1. EITHER: Less than 5 years since clinical diagnosis of PD and mild to moderate UPDRS III OFF score
  2. OR: At least 4 years since clinical diagnosis of PD and moderate to severe UPDRS III OFF score
• Responsiveness to levodopa

Exclusion Criteria

• Atypical parkinsonism
• Severe dyskinesia
• Presence of dementia, psychosis, substance abuse or qualify as "severe depression"
• Prior brain surgery (i.e. deep brain stimulator or DBS implantation) or other brain imaging abnormalities
• Receiving an investigational drug
• History of cancer or poorly controlled medical conditions that would increase surgical risk
• Inability to tolerate laying flat in an MRI or allergy to gadolinium

Contact:

OSUgenetherapyresearch@osumc.edu

Link:

https://clinicaltrials.gov/ct2/show/NCT04167540?term=AAV2-GDNF&draw=2&rank=2

Sponsor:

Brain Neurotherapy Bio, Inc.

Purpose of the Study: 

This study is being done to find out if light therapy can help people with Parkinson’s disease (PD) who experience difficulties with their sleep. We also want to find out if light therapy is safe and does not cause too many side effects.

If you qualify to join, it will take you about 4 months to complete this research study. During this time, we will ask you
to make 5 study visits to The Ohio State University and complete 3 phone calls.

Eligibility Criteria:

• Diagnosis of idiopathic PD
• Stable dose of all PD medications for at least 30 days prior to randomization
• Willingness to wear an Actiwatch and complete daily sleep logs

Exclusion Criteria:

• Presence of moderate depression
• Co-existent significant sleep apnea
• Co-existent symptomatic restless legs syndrome (RLS)
• Cognitive impairment
• Pregnant women

Research Team:

Principal Investigator: Stephen Kolb, MD, PhD

Co-Investigator: Warren Lo, MD

Coordinator: Amy Bartlett, CCRC  Contact Email: Amy.Bartlett@osumc.edu  Contact Phone: 614-366-9050

Link:

https://neuronext.org/projects/nn110-enlite-pd

Purpose of the Study: 

Parkinson's disease (PD) is a neurodegenerative disorder involving loss of dopamine producing neurons located in the striatum. Levodopa is the primary treatment used to treat Parkinson's disease, which converts to dopamine by the enzyme (protein) Aromatic L-Amino Acid Decarboxylase (AADC). As PD progresses, the amount of AADC levels in the brain decreases, and in turn, reduces the amount of dopamine that is produced with each dose of levodopa.

The primary objective of this study is to evaluate the safety of increasing AADC levels, via gene delivery. The investigational drug, termed VY-AADC-01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery.

Participants will continue to take their Parkinson medications, including levodopa while participating in this study.

The safety and potential clinical responses to VY-AADC-01 will be assessed by repeated clinical evaluations of Parkinson's disease, treatment review phone calls, cognitive tests, laboratory blood tests, patient reported outcomes scales, patient diaries, collection of adverse events, and neuro-imaging. Clinical evaluations will be performed over a 3 year follow-up period. 

Eligibility Criteria:

• Diagnosed with idiopathic PD.
• Adequate duration of levodopa therapy.
• Disease duration of at least 5 years or more.
• Modified Hoehn & Yahr Staging with at least 2.5 hours or more in the OFF state.
• Candidate for surgical intervention because of disabling motor complications.
• UPDRS Part III (total score) of at least 25 in the OFF state.
• Unequivocal responsiveness to dopaminergic therapy.
• Stable Parkinson's symptoms and medications for at least 4 weeks prior to screening evaluation.
• Ability to comprehend and sign the informed consent.
• Normal laboratory values prior to surgery.
• Medically and mentally capable of undergoing and complying with the surgical procedure and protocol requirements.
• Ability to travel to study visits alone or able to designate a caregiver.
• Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).Approved by the Eligibility Review Committee. 

Link:

https://clinicaltrials.gov/ct2/show/NCT03065192?term=PD-1102&draw=2&rank=1

 

Purpose of the Study: 

A Phase 3 study to evaluate efficacy, safety, and tolerability of ampreloxetine (TD-9855) in subjects with primary autonomic failures (MSA, PD, or PAF) and symptomatic nOH with up to 4 weeks of treatment.

Eligibility Criteria:

• Subject is male or female and at least 30 years old.
• Subject must meet the diagnostic criteria of symptomatic nOH, as demonstrated by a sustained reduction in BP of ≥20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3 minutes of being tilted-up to ≥60o from a supine position as determined by a tilt-table test.
• Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit.
• For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria (1992).
• For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
• For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization.
• Subject has plasma NE levels >100 pg/mL after being in seated position for 30 minutes.

Exclusion Criteria

• Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis, and autoimmune neuropathies.
• Subject has a known intolerance to other NRIs or SNRIs.
• Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension unrelated to autonomic dysfunction.
• Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization or requires concomitant use until the follow-up visit.

• Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to V1.

  • Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1.
• Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
• Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
• Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
• Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject.
• Subject has any significant uncontrolled cardiac arrhythmia.
• Subject has a Montreal Cognitive Assessment (MoCA) ≤23.
• Subject had a myocardial infarction in the past 6 months or has current unstable angina.
• Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
• Subject has a clinically significant abnormal laboratory findings (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3.0 x upper limit of normal [ULN]; blood bilirubin [total] >1.5 x ULN; estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2, or any abnormal laboratory value that could interfere with safety of the subject).
• Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Columbia Suicide Severity Rating Scale) (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject's appropriateness for inclusion in the study.

Link:

https://clinicaltrials.gov/ct2/show/NCT03750552?term=TD-9855&draw=2&rank=4

Sponsor:

Theravance Biopharma

Purpose of the Study: 

This is a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of Valbenazine to treat chorea in subjects with Huntington disease.

Eligibility Criteria:

• Have a clinical diagnosis of Huntington Disease (HD) with chorea
• Be able to walk, with or without the assistance of a person or device
• Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study
• Be able to read and understand English

Exclusion Criteria

• Have a history of prior VMAT2 inhibitor therapy
• Have difficulty swallowing
• Are currently pregnant or breastfeeding
• Have a known history of long QT syndrome, cardiac tachyarrhythmia, left bundle-branch block, atrioventricular (AV) block, bradycardia (<60 bpm), or heart failure
• Have an unstable or serious medical or psychiatric illness
• Have a significant risk of suicidal behavior
• Have current substance dependence or substance (drug) or alcohol abuse
• If taking antidepressant therapy, be on a stable regimen
• Have received gene therapy at any time
• Have received an investigational drug within 30 days before the baseline visit or plan to use an investigational drug (other than valbenazine) during the study
• Have had a blood loss ≥550 mL or donated blood within 30 days before the baseline visit

Link:

 https://clinicaltrials.gov/ct2/show/NCT04102579?term=KINECT-HD&cond=Huntington+Disease&draw=2&rank=1

Sponsor:

Neurocrine Biosciences

Status:

Recruiting

 

Purpose of the Study: 

This is a Phase 3, open-label study to evaluate the long-term safety and tolerability of valbenazine, and to provide subjects continued access to valbenazine for the treatment of chorea associated with Huntington disease.

Eligibility Criteria:

• Have participated in in Study NBI-98854-HD3005 and: a)Study drug dosing completion of Study NBI-98854-HD3005, as demonstrated by completed study drug dosing through the end of treatment period; b) Early terminated Study NBI-98854-HD3005 for administrative reasons due to COVID-19 (eg, site closure related to COVID-19).
• Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently while participating in the study until 30 days (females) or 90 days (males) after the last dose of the study drug.

Exclusion Criteria

• Are currently pregnant or breastfeeding
• Have difficulty swallowing
• Have a known history of long QT syndrome, cardiac tachyarrhythmia, left bundle-branch block, atrioventricular (AV) block, uncontrolled bradyarrhythmia, or heart failure
• Have an unstable or serious medical or psychiatric illness
• Have a significant risk of suicidal behavior
• Have current substance dependence or substance (drug) or alcohol abuse
• Have received gene therapy at any time
• Have received an investigational drug (other than valbenazine) within 30 days before the baseline visit or plan to use an investigational drug (other than valbenazine) during the study
• Have had a blood loss ≥550 mL or donated blood within 30 days before the baseline visit
• Have a history of severe hepatic impairment or history of protocol specified hematologic abnormalities during the course of the NBI-98854-HD3005 study
• Had a medically significant illness within 30 days before baseline, or any history of neuroleptic malignant syndrome

Link:

 https://clinicaltrials.gov/ct2/show/NCT04400331?term=valbenazine&cond=Huntington+Disease&draw=2&rank=1

Sponsor:

Neurocrine Biosciences

Status:

Recruiting (Only open to patients who complete KINECT-HD)

 

Purpose of the Study: 

This is the first study of AMT-130 in patients with early manifest HD and is designed to establish safety and proof-of-concept (PoC). CT-AMT-130-01 is a Phase I/II, randomized, multicenter, dose escalation, double-blind, imitation surgery, first-in-human (FIH) study.

Eligibility Criteria:

• Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic classification level (DCL) of 4 OR a DCL of 3 if the subject either meets the definition of multidimensional manifest HD (UHDRS question 80) or has cognitive symptoms
• HTT gene expansion testing with the presence of ≥40 CAG repeats.
• Striatal MRI volume requirements per hemisphere: Putamen ≥2.5 cm3 (per side); Caudate ≥2.0 cm3 (per side)
• All HD concomitant medications (addressing motor, behavioral, and cognitive symptoms) stable for 3 months prior to Screening.
• Able and willing to provide written informed consent
• Able and willing to comply with all procedures and study visits

Exclusion Criteria

• Evidence of suicide risk
• Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
• Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation, etc.) within 60 days prior to Screening or anytime over the duration of this study.
• Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter
• Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASO), cell transplantation or any other experimental brain surgery.
• Any contraindication to lumbar puncture or 3.0 Tesla MRI as per local guidelines.
• Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder.
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
• Current or recurrent disease, infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule

Link:

https://clinicaltrials.gov/ct2/show/NCT04120493?term=CT-AMT130-01&draw=2&rank=1

Sponsor:

UniQure Biopharma B.V.

Status:

Recruiting

 

Purpose of the Study: 

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pridopidine 45 mg BID in patients with early stage HD. Eligible patients who completed the Main Study (65 to 78 weeks) will have the option to enroll into an open-label extension.

Eligibility Criteria:

• Diagnosis of HD based on clinical features and the presence of ≥36 CAG repeats in the huntingtin gene
• Diagnostic confidence level (DCL) of 4
• Adult-onset HD with onset of signs and symptoms ≥18 years of age
• Stage 1 or Stage 2 HD, defined as a UHDRS-TFC score of ≥7, at screening

Exclusion Criteria

• Use of pridopidine within 12 months before the baseline visit.
• Gene therapy at any time
• Any serious medical condition or clinically significant laboratory, or vital sign abnormality that precludes the patient's safe participation in and completion of the study e.g. significant heart disease within 12 weeks before baseline or history of certain cardiac arrhythmias
• History of epilepsy or seizures within the last 5 years
• Pregnant or breastfeeding, or intention to become pregnant during the study

Link:

https://clinicaltrials.gov/ct2/show/NCT04556656?term=PROOF-HD&cond=huntington&draw=1&rank=1

Sponsor:

Prilenia

Status:

Pending

 

Purpose of the Study: Enroll-HD is a longitudinal, observational, multinational study that will integrate two existing Huntington’s Disease (HD) registries, REGISTRY in Europe and COHORT in North America and Australia, while also expanding to include sites in Latin America and Asia. With no end date and annual assessments, the goal of Enroll-HD is to build a large and rich database of longitudinal clinical information and biospecimens. This database will serve as a basis for future studies aimed at developing tools and biomarkers for progression and prognosis, identifying clinically relevant phenotypic characteristics and establishing clearly defined endpoints for interventional studies.

Description of Study: The primary objective of Enroll-HD is to develop a comprehensive repository of prospective and systematically collected clinical research data (demography, clinical features, family history, genetic characteristics) and biological specimens (blood) from individuals with manifest HD, unaffected individuals known to carry the HD mutation or to be at risk of carrying the HD mutation, and control research participants (e.g., spouses, siblings or offspring of HD mutation carriers known not to carry the HD mutation). Enroll-HD is conceived as a broad-based and long-term project to maximize the efficiencies of non-clinical research and participation in clinical research. With more than 200 sites in roughly 30 countries, Enroll HD will be the largest database available for HD researchers.

Eligibility Criteria:

• Carriers: This group comprises the primary study population and consists of individuals who carry the HD gene expansion mutation.
• Controls: This group comprises the comparator study population and consists of individuals who do not carry the HD expansion mutation.

These two major categories can be further subdivided into six different subgroups of eligible individuals:

• Manifest/Motor-manifest HD: Carriers with clinical features that are regarded in the opinion of the investigator as diagnostic of HD
• Pre-Manifest/-Motor-manifest HD: Carriers without clinical features regarded as diagnostic of HD
• Genotype Unknown: This group includes a first- or second-degree relative (i.e., related by blood to a carrier) who has not undergone predictive testing for HD and therefore has an undetermined carrier status
• Genotype Negative: This group includes a first- or second-degree relative (i.e., related by blood to a carrier)  who has undergone predictive testing for HD and is known not to carry the HD expansion mutation
• Family Control: Family members or individuals not related by blood to carriers (e.g., spouses, partners, caregivers)
• Community Controls: Individuals unrelated to HD carriers who did not grow up in a family affected by HD. Data collected from community controls will be used for generation of normative data for sub-studies

Status of Study: Recruiting

Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672

Purpose of Study: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of SD-809 ER in subjects switching from tetrabenazine to SD-809 ER. In addition, the safety and tolerability of long-term treatment with SD-809 ER will be assessed in “Switch” subjects as well as “Rollover” subjects completing a randomized, double-blind, placebo-controlled study of SD-809 ER.

Eligibility Criteria: Men and women age 18 and older who have been diagnosed with manifest HD, as indicated by characteristic motor exam features, and who have a documented expanded CAG repeat (≥ 37) at or before screening. Subjects must meet either of the following:

• Have successfully completed participation in the First-HD Study (SD-809-C-15) OR
• Have been receiving an FDA-approved dose of tetrabenazine that has been stable for ≥ 8 weeks before screening and is providing a therapeutic benefit for control of chorea.

Also:

Subjects have a Total Functional Capacity (TFC) score ≥ 5 at screening.

Subjects are able to swallow study medication whole.

Subjects have provided written, informed consent, or a legally authorized representative (LAR) has provided written informed consent and the subjects have provided assent.

Subjects have provided a Research Advance Directive.

Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion.

Subject have a reliable caregiver who interacts with them daily, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required.

Subjects are able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices [e.g., walker, cane] are permitted during ambulation).

Subjects have sufficient reading skills to comprehend the subject-completed rating scales.

Status of Study: Ongoing, not recruiting

Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
email: Allison.Daley@osumc.edu

Sponsor: Auspex Pharmaceuticals, Inc.

Purpose of Study: This is a 12-month, open-label, extension study of PF-02545920 20 mg-dosed BID following study A8241021 in subjects with HD. Primary endpoints will be to assess long-term safety and tolerability of 20 mg BID of PF-02545920. Secondary endpoints will be the change from baseline in the Total Motor Score (TMS)assessment, and/or the Total maximum Chorea (TMC) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after six and 12 months of treatment, and Clinical Global Impression-Improvement score after six and 12 months of treatment.

Description of Study: Subjects who were assigned to the 20 mg PF-02545920-dose group in the preceding A8241021 study will receive 20 mg PF-02545920 without any titration. All other subjects will be titrated to the 20 mg BID dose as follows: 5 mg BID for seven days, 10 mg BID for seven days, 15 mg BID for seven days, then 20 mg BID for the remainder of the treatment phase. Up to 260 subjects may take part in this open-label extension.

Eligibility Criteria: Men and women age 30 to 65 who have completed study A8241021 and have a diagnosis of HD, including ≥36 CAG repeats.

Status of Study: Recruiting

Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
email: Allison.Daley@osumc.edu

Sponsor: Pfizer

Purpose of Study: This study is a 26-week, randomized, parallel-group, double-blind comparison of PF-02545920 5 mg, PF-02545920 20 mg and placebo-dosed BID in the treatment of motor impairment of subjects with Huntington’s disease.

Description of Study: Investigators plan to randomize approximately 260 subjects in the study. Primary endpoint is the change from baseline in the Total Motor Score (TMS) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 26 weeks of treatment. Secondary endpoints will include change from baseline in the Total Maximum Chorea (TMC) score of the UHDRS after 13 and 26 weeks of treatment and Clinical Global Impression-Improvement score after 13 and 26 weeks of treatment.

Eligibility Criteria: Men and women age 30 to 65 with CAG repeat equal to or greater than 36; total motor score equal to or greater than 10; total functional capacity equal to or greater than 7 are eligible.

Status of Study: Recruiting

Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
email: Allison.Daley@osumc.edu

Sponsor: Pfizer

Purpose of Study: Individuals with dementia with Lewy Bodies (DLB) and Huntington’s disease (HD) experience balance and walking problems that lead to falls. Treadmill walking has demonstrated improvements in balance walking and fall risk in individuals with Parkinson’s disease (PD), suggesting that it may be beneficial for individuals with DLB and HD. In PD subjects, changes in gait parameters have been noted after only one treadmill training session. The investigators propose a pilot study to investigate the safety, feasibility and utility of trying to improve mobility and fall risk through a single session of treadmill walking in individuals with DLB and HD.

Description of Study: Several studies using HD animal models have shown that HD mice housed in enriched environments or in cages with running wheels that stimulated physical activity demonstrated a delayed onset and/or slowed decline in motor function compared to mice in non-enriched environments (van Dellen et al. 2000, 2008; Spires et al., 2004).

Evidence suggests that aerobic exercise may have neuroprotective effects and helps the elderly and individuals with neurodegenerative diseases to maintain better cognitive and motor function than those who are inactive. More specifically, there is strong evidence from animal and human trials in neurological populations (e.g., Parkinson’s disease, spinal cord injury, stroke) that treadmill training can improve walking and motor function. Immediate effects of a single-session of treadmill walking in the Parkinson’s disease population were improved overground gait measures (e.g., gait speed, stride length, double support percent, stride variability), and longer-term treadmill training studies demonstrated additional improvements in Unified Parkinson Disease Rating Scale scores, fall risk and health-related quality of life (Herman et al., 2008).

This study builds upon foundational knowledge gained in animal and other neurologic populations to determine the feasibility, safety and possible immediate benefit of treadmill walking in individuals with HD. The primary purpose of this pilot study is to investigate the safety, feasibility and utility of a single 20-minute session of treadmill walking to improve gait parameters in ambulatory individuals with DLB and HD.

Secondarily we will explore the effects of treadmill walking on mobility, fall risk, and motor coordination. Based on previous studies utilizing a single session of treadmill training in the PD population, we hypothesize that treadmill walking will improve overground spatiotemporal gait parameters (gait speed, stride length, double support percent and stride-to-stride variations in gait) in individuals with DLB and HD (Pohl et al., 2003; Frenkel-Toledo et al., 2005; Bello et al., 2008).

Eligibility Criteria: Men and women age 18 to 20 with a diagnosis of Huntington’s disease or Dementia with Lewy Bodies, the ability to ambulate 80 feet without assistance, and the ability to provide informed consent and understand directions are eligible.

Status of Study: Recruiting

Co-Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
email: Allison.Daley@osumc.edu

Sponsor: The Ohio State University

Purpose of Study: The purpose of this study is to evaluate the safety, tolerability, PK and efficacy of VX15/2503 in subjects with late-prodromal and early-manifest Huntington's disease.

Description of Study: VX15/2503-N-131 is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study of VX15/2503 in subjects with late-prodromal and early-manifest Huntington's disease. The primary objective is to evaluate the safety and tolerability of monthly IV administration of a single dosage of VX15/2503 (or placebo). Secondary objectives include determining the effect of VX15/2503 on brain volumes (MRI), FDG-PET imaging and clinical features of HD including cognition, motor function, behavior, functional abilities and global function. Additional secondary objectives include PK / PD, immunogenicity and exploratory biomarkers.

Enrollment will involve approximately 84 individuals who are 21 years of age or older with late-prodromal (CAG-age product score [CAP score] of greater than 200 and Diagnostic Confidence Level [DCL] of 2 or 3) or early-manifest HD (Total Functional Capacity (TFC) greater than or equal to 11). The study will be divided into Cohort A and Cohort B.

Cohort A subjects will be treated for six months with either drug or placebo (1:1), and then all subjects will be treated with drug for six months, followed by three months of follow up. Treatment duration for each subject will be 12 months. Participation in Cohort A will include a screening visit, a baseline visit within 30 days of screening, 12 monthly treatment visits beginning at baseline and continuing through month 12, a follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort A subjects will participate in the study for approximately 16 months.

Cohort B subjects will be treated with drug or placebo (1:1) for 18 months, followed by three months of follow up. Treatment duration for each subject will be 18 months. (The duration of treatment may be reduced to 12 months based on the outcome of the analysis of the data from Cohort A.) Participation in Cohort B will include a screening visit, a baseline visit within 30 days of screening, 18 monthly treatment visits beginning at baseline and continuing through month 18, a follow-up safety phone call at one month and a follow-up safety visit three months after the final infusion. Cohort B subjects will participate in the study for approximately 22 months.

Eligibility Criteria: Male or female at least 21 years of age at screening.

Must fulfill one of the following criteria at screening:

• Late-prodromal HD as defined by a CAP score of greater than 200 and DCL 2 or 3,
• Early-manifest HD as defined by a TFC greater than or equal to 11. Subject must have been given a clinical diagnosis of HD

Must fulfill both of the following criteria at screening:

• Have undergone genetic testing with a known CAG repeat greater than or equal to 36
• Have no features of juvenile HD (Westphal variant).

Females must be either surgically sterile, postmenopausal or nonlactating and nonpregnant. Female subjects of childbearing potential must practice a highly effective method of contraception

Males must agree to use a reliable method of birth control

Subjects are willing and capable of providing informed consent for study participation and CAG genotyping (all subjects)

Subjects are capable of reading, writing and communicating effectively with others

Subjects are taking stable doses of any concomitant medications (including tetrabenazine) during the month prior to the baseline visit, and dosing must remain stable throughout the study.

Status of Study: Recruiting

Principal Investigator: Sandra Kostyk, MD, PhD

Contact:
Allison Daley, MS, MPH
Phone: 614-688-8672, Fax: 614-366-8672
email: Allison.Daley@osumc.edu

Sponsor: Vaccinex, Inc.

Collaborator: Huntington Study Group

Purpose of Study: The objective of this prospective, multisite, single-arm study is to capture the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in patients with essential tremor (ET).

Description of Study: This study is evaluating a new technique for performing thalamotomy for tremor control. While current techniques have possible invasive or radiation effects, the use of ExAblate is non-invasive and without radiation. After informed consent and screening, eligible subjects will undergo an ExAblate treatment. All subjects will be followed at one day; one week; one, three, six and 12 months; and for up to five years as directed by their doctor.

Eligibility Criteria: Men and women age 22 and older with a diagnosis of essential tremor, as confirmed by clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder, and significant disability from their ET despite medical treatment. Subjects should be on a stable dose of all ET medications for 30 days prior to study entry, able to communicate sensations during the ExAblate transcranial procedure, and able and willing to give informed consent and attend all study visits.

Status of Study: Recruiting

Contacts:
Phuong (Lina) Nguyen, MBA, CCRP
Phone: 614-366-6952
Email: phuong.nguyen2@osumc.edu

Amelia Hargrove
Phone: 614-366-6639
Email: amelia.hargrove@osumc.edu

Sponsor: Insightec