Back to resultsOpen-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
Primary Purpose
Primary Mitochondrial Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
elamipretide
Sponsored by
About this trial
This is an interventional treatment trial for Primary Mitochondrial Disease focused on measuring Primary Mitochondrial Disease, Stealth, elamipretide
Eligibility Criteria
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
Sites / Locations
- University of California
- Massachusetts General Hospital
- Akron Children's Hospital
- Children's Hospital of Pittsburgh of UPMC
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
elamipretide
Arm Description
Open-label once daily subcutaneous injection of 40mg elamipretide
Outcomes
Primary Outcome Measures
Distance Walked on Six Minute Walk Test
Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02976038
First Posted
November 18, 2016
Last Updated
November 19, 2021
Sponsor
Stealth BioTherapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02976038
Brief Title
Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Terminated
Why Stopped
Registration trial did not meet the primary end points
Study Start Date
December 2016 (Actual)
Primary Completion Date
March 9, 2020 (Actual)
Study Completion Date
April 9, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stealth BioTherapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Mitochondrial Disease
Keywords
Primary Mitochondrial Disease, Stealth, elamipretide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
elamipretide
Arm Type
Experimental
Arm Description
Open-label once daily subcutaneous injection of 40mg elamipretide
Intervention Type
Drug
Intervention Name(s)
elamipretide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Distance Walked on Six Minute Walk Test
Description
Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Secondary Outcome Measure Information:
Title
EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Euroquol Visual Analog Scale
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
NeuroQOL Fatigue Questionnaire
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Patient Global Assessment : Categorical
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Patient Global Assessment: Continuous Variable
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Work Limitations Questionnaire
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Physician Global Assessment Score (PhGA) by Visit
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Physician Global Assessment (PhGA): Categorical
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
PMMSA Individual Items
Description
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.
Time Frame
Baseline, Week 13, 26, 52, 104, 156, End of Study (Week 160)
Title
Total Fatigue Score_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
Title
Total Fatigue Score During Activities_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
Description
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.
Time Frame
Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jim Carr, PharmD
Organizational Affiliation
Stealth BioTherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of California
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
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