Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)

Study Overview
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Brief Summary
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This is a Phase 2 Open-Label extension study to evaluate the long term safety and tolerability of daily elamipretide injections in patients with genetically confirmed Primary Mitochondrial Disease who previously participated in the SPIMM-202 Clinical Trial

Detailed Description
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This open-label, non-comparative, extension trial will enroll subjects with genetically confirmed PMD who have completed the End-of-Study Visit in the SPIMM-202 trial. Subjects who do not discontinue or withdraw from the trial will receive treatment with 40 mg SC elamipretide for the shortest of the following: 260 weeks; regulatory approval and commercial availability of elamipretide in the subject's respective country; or termination of the clinical development for elamipretide in subjects with PMD.

Official Title
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A Multicenter, Open-Label Phase 2 Extension Trial to Characterize the Long-term Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)

Conditions
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Primary Mitochondrial Disease

Intervention / Treatment
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* Drug: elamipretide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Investigator determines the subject can, and subject agrees to, adhere to the trial requirements for the length of the trial including self-administration (by subject or trained caregiver) of the study drug Subject completed the End-of-Study Visit in SPIMM-202 Exclusion Criteria: Subject has any prior or current medical condition that, in the judgment of the Investigator, would prevent the subject from safely participating in and/or completing all trial requirements Subject has received any investigational compound (excluding elamipretide) and/or has participated in another interventional clinical trial within 30 days prior to the SPIMM-203 Baseline Visit (excluding SPIMM-202) or is concurrently enrolled in any non-interventional research of any type judged to be scientifically or medically incompatible with the trial as deemed by the Investigator in consultation with the Sponsor Subject experienced an adverse reaction attributed to study drug resulting in permanent discontinuation of study drug in the SPIMM-202 trial. Female subjects who are pregnant, planning to become pregnant, or lactating Subject has undergone an in-patient hospitalization within the 1 month prior to the SPIMM-203 Baseline Visit

Ages Eligible for Study
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Minimum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: elamipretide<br>Open-label once daily subcutaneous injection of 40mg elamipretide | Drug: elamipretide<br>* 40 mg, subcutaneous injections (in the abdomen) daily for the shortest of the following: 260 weeks; regulatory approval and commercial availability of elamipretide in the subject's respective country; or termination of the clinical development for elamipretide in subjects with PMD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distance Walked on Six Minute Walk Test | Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) | EuroQol 5 dimensions 5 levels (EQ-5D-5L) by visit. Count of participants per arm, or severity level of dimension. Measures 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Score ranges from 5-25 with lower score=better outcome, and higher score means a worse outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Euroquol Visual Analog Scale | Euroquol Visual Analog Scale (EQ VAS): A patient-reported measure. The visual scale is numbered from 0 to 100, participants are directed as follows: 100 means the best health you can imagine, 0 means the worst health you can imagine. Mark an X on the scale to indicate how your health is TODAY. Higher scores mean better outcome, lower scores mean worse outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| NeuroQOL Fatigue Questionnaire | Change from baseline in NeuroQOL Fatigue Questionnaire by visit. Questionnaire is comprised of 8 questions measuring participants incidence of fatigue affecting activities of daily living. Participants respond by choosing one of the following: 1=never, 2=rarely, 3=sometimes, 4=often, 5=always, with a lower score meaning a better outcome with fatigue affecting participant less, and high score meaning a worse outcome, with fatigue affecting the participant more. Total raw scores range from 8-40. Scores were converted to percentages: range0-100%. Change from baseline score: negative number means improved from baseline, positive number means worsened compared to baseline. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Patient Global Assessment : Categorical | Patient Global Assessment [PGA] Score by Visit, count of participants. Patient-reported current health status by visit. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Total score ranges from 1-5. Higher score means worse health status, means worse outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Patient Global Assessment: Continuous Variable | Patient Global Assessment [PGA] Score by Visit, Patient-reported current health status by visit. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Total score ranges from 1-5. Higher score means worse health status, lower score means worse outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Work Limitations Questionnaire | Work Limitations Questionnaire by visit. Comprised of 25 items, in 4 categories, or demands: Mental/Interpersonal, Output Tasks, Physical Tasks, and Time Management, measuring the degree to which employed individuals are experiencing limitations on-the-job due to their health problems, and health-related productivity loss. 1= All of the time (100%), 2= most of the time, 3=some of the time (about 50%), 4=slight bit of time, 5=none of the time (0%), 6=does not apply to my job. (Presenteeism). The WLQ items ask respondents to rate their level of difficulty or ability to perform specific job demands. Scale score range from 0 (limited none of the time=better outcome) to 100 (limited all of the time= worse outcome) and represent the reported amount of time in the prior two weeks respondents were limited on-the-job. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Physician Global Assessment Score (PhGA) by Visit | Physician Global Assessment- Mean Score by visit. PGA Scale asks physician to rate participant's current health status as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Total score ranges from 1-5. Higher score means lower health status, worse outcome; lower score means better health status, better outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Physician Global Assessment (PhGA): Categorical | Physician Global Assessment [PhGA] Score by Visit, Physician-reported current health status by visit. PhGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Total score ranges from 1-5. Higher score means worse health status, means worse outcome. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| PMMSA Individual Items | The PMMSA is a patient-reported outcome measure, assessing a participant's worst feeling of 10 symptoms during the last 24 hours: tiredness at rest, tiredness during activities, muscle weakness at rest, muscle weakness during activities, balance, vision, abdominal discomfort, muscle pain, numbness, and headache using a 4-point scale: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Max Score =40= worse outcome, Min score= 10= better outcome on scale. PMMSA Individual Items shows number or participants with mild, moderate, severe or no symptoms at all. | Baseline, Week 13, 26, 52, 104, 156, End of Study (Week 160) | 
| Total Fatigue Score_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) | Change from baseline in the Total Fatigue score Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) where participants report their worst feeling of 4 symptoms: Tiredness at rest, Tiredness during activities, Muscle weakness at rest, Muscle weakness during activities, at the end of each treatment period. Total fatigue score is sum of Q1 to Q4 only of PMMSA) and is scored as follows: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Total score range is 4-16; lower score means less fatigue and better outcome, higher score means more fatigue and worse outcome. Raw scores were transformed into percentages: 0-100%. Change from baseline: the lower the score, the better the outcome,=less fatigue; the higher the score, means worse outcome= more fatigue. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 
| Total Fatigue Score During Activities_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) | Change from baseline in the Total Fatigue during Activities score Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) where participants report their worst feeling of 2 symptoms: Tiredness during activities, Muscle weakness during activities, at the end of each treatment period. Total fatigue score is sum of Q2 and Q4 only of PMMSA) and is scored as follows: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Total score range is 2-8; lower score means less fatigue and better outcome, higher score means more fatigue and worse outcome. Raw scores were transformed into percentages: 0-100%. Change from baseline: the lower the score, the better the outcome,=less fatigue; the higher the score, means worse outcome= more fatigue. | Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Mitochondrial Disease, Stealth, elamipretide