Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation

Study Overview
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Brief Summary
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This is a phase 2a, double-blind, placebo-controlled, single-center study. Twenty-one patients who qualify for the study will be randomly assigned to either active drug or placebo. The study will take place at Newcastle University. Patients will have a 66% chance of getting active drug. Patients will be required to take study treatment orally twice a day for 28 days. A baseline visit will occur within 21 days of screening visit. All patients will be followed for 1 week after completion of study or early withdrawal from the study.

Official Title
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A Phase 2a, Double Blind, Randomized, Placebo-controlled, 28 Day, Two-arm, Parallel Group Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation and Evidence of Impaired Mitochondrial Function

Conditions
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Neuromuscular Disease

Intervention / Treatment
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* Drug: A0001 (alpha-tocopherolquinone)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of neuromuscular symptoms due to the A3243G mitochondrial DNA point mutation PCR/ATP ratio of <1.9 following the Cardiac MRS at screening Exclusion Criteria: Any major illness not due to the A3243G mitochondrial DNA point mutation in the past three months or any significant ongoing chronic medical illness, especially significant central nervous neurological disease limiting capacity to carry out the study Use of any investigational product within the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A0001<br>A0001 (0.75 g BID) | Drug: A0001 (alpha-tocopherolquinone)<br>* 28 days (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 28 days of placebo oral capsules. Treatment taken twice daily with meals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in the rate of ATP recovery (Vmax) in cardiac muscle as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) |  | Baseline and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in cardiac structure and function as measured by Magnetic Resonance Imaging (MRI) |  | Baseline and Day 28 | 
| Exercise tolerance as measured by a 6 minute walk test |  | Baseline, Day 14 and Day 28 | 
| Improvement in the rate of Maximal ATP recovery (Vmax) as measured by 31Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) MRI of calf muscle during a standardized isolated calf muscle procedure of 2 bouts of plantar flexion exercise |  | Baseline and Day 28 | 
| Fasting blood lactate, fasting blood glucose, fasting blood insulin , fasting blood HbA1c levels |  | Baseline, Day 14 and Day 28 | 
| Mitochondrial disease severity (NMDAS) |  | Baseline and Day 28 | 
| Quality of life (SF-36® Health Survey Questionnaire) |  | Baseline and Day 28 | 
| Global impression of clinical severity |  | Baseline, Day 14 and Day 28 | 
| Modified fatigue impact scale |  | Baseline, Day 14 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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A3243G Mitochondrial DNA Point Mutation