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

• Sponsor: Stealth BioTherapeutics Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02976038
• Collaborator: (none)
• Enrollment: 28
• Locations: 4
• Arm: 1
• Actual Duration (Months): 40.2
• Patients Per Site: 7
• Patients Per Site Per Month: 0.2

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Primary Mitochondrial Disease	Drug: elamipretide	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Mar 9, 2020
• Actual Study Completion Date: Apr 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: elamipretide Open-label once daily subcutaneous injection of 40mg elamipretide	Drug: elamipretide; 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.

Outcome Measures

Primary Outcome Measures

1. Distance Walked on Six Minute Walk Test [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit

Secondary Outcome Measures

1. EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

2. Euroquol Visual Analog Scale [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

3. NeuroQOL Fatigue Questionnaire [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

4. Patient Global Assessment : Categorical [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

5. Patient Global Assessment: Continuous Variable [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

6. Work Limitations Questionnaire [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

7. Physician Global Assessment Score (PhGA) by Visit [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

8. Physician Global Assessment (PhGA): Categorical [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

   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.

9. PMMSA Individual Items [Baseline, Week 13, 26, 52, 104, 156, End of Study (Week 160)]

   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.

10. Total Fatigue Score_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

    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.

11. Total Fatigue Score During Activities_Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) [Baseline, Month 3, Month 6 and Every 26 weeks for up to 160 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California	San Diego	California	United States	92123
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Akron Children's Hospital	Akron	Ohio	United States	44308
4	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224

Sponsors and Collaborators

• Stealth BioTherapeutics Inc.

Investigators

• Study Director: Jim Carr, PharmD, Stealth BioTherapeutics

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 29, 2019

More Information

Publications

None provided.

• Responsible Party: Stealth BioTherapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02976038
• Other Study ID Numbers: SPIMM-203
• First Posted: Nov 29, 2016
• Last Update Posted: Dec 17, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Stealth BioTherapeutics Inc.: Primary Mitochondrial Disease; Stealth; elamipretide
• Additional relevant MeSH terms: Mitochondrial Myopathies; Mitochondrial Diseases

Study Results

Participant Flow

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Period Title: Overall Study
STARTED	28
COMPLETED	0
NOT COMPLETED	28

Baseline Characteristics

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.8 (11.30)
Sex: Female, Male (Count of Participants)
Female	24 85.7%
Male	4 14.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%
Not Hispanic or Latino	27 96.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	27 96.4%
More than one race	1 3.6%
Unknown or Not Reported	0 0%
Baseline weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	65.93 (14.614)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit was measured.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Week 13	3.6 (52.68)
Week 26	-8.6 (56.33)
Week 52	-17.6 (70.60)
Week 78	-26.2 (73.17)
Week 104	-20.9 (77.78)
Week 130	-18.9 (76.94)
Week 156	-35.0 (NA)
End of Trial (Week 160)	-54.0 (70.30)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom EQ-5D-5L was measured. Trial was terminated early.

Arm/Group Title	No Problem	Slight Problem	Moderate Problem	Severe Problem	Extreme Problem
Arm/Group Description	Participant reports symptom is "no problem"	Participant reports symptom is a "slight problem"	Participant reports symptom is a "moderate problem"	Participant reports symptom is a "severe problem"	Participant reports symptom is an "extreme problem"
Measure Participants	28	28	28	28	28
Baseline: Anxiety/Depression	12 42.9%	8 NaN	4 NaN	3 NaN	1 NaN
Baseline: : Mobility	2 7.1%	10 NaN	11 NaN	5 NaN	0 NaN
Baseline: : Pain/Discomfort	4 14.3%	5 NaN	15 NaN	4 NaN	0 NaN
Baseline: : Self-Care	12 42.9%	10 NaN	5 NaN	0 NaN	1 NaN
Baseline: : Usual Activities	5 17.9%	7 NaN	12 NaN	4 NaN	0 NaN
Week 13 Anxiety/Depression	16 57.1%	6 NaN	5 NaN	1 NaN	0 NaN
Week 13 : Mobility	7 25%	7 NaN	12 NaN	1 NaN	1 NaN
Week 13 : Pain/Discomfort	4 14.3%	12 NaN	8 NaN	3 NaN	1 NaN
Week 13 : Self-Care	18 64.3%	7 NaN	2 NaN	0 NaN	1 NaN
Week 13 : Usual Activities	6 21.4%	15 NaN	5 NaN	0 NaN	2 NaN
Week 26 Anxiety/Depression	16 57.1%	6 NaN	5 NaN	0 NaN	0 NaN
Week 26 : Mobility	5 17.9%	6 NaN	12 NaN	4 NaN	0 NaN
Week 26 : Pain/Discomfort	8 28.6%	11 NaN	5 NaN	2 NaN	1 NaN
Week 26 : Self-Care	17 60.7%	7 NaN	3 NaN	0 NaN	0 NaN
Week 26 : Usual Activities	6 21.4%	13 NaN	7 NaN	1 NaN	0 NaN
Week 56 Anxiety/Depression	14 50%	5 NaN	4 NaN	1 NaN	1 NaN
Week 56 : Mobility	6 21.4%	6 NaN	4 NaN	9 NaN	0 NaN
Week 56 : Pain/Discomfort	6 21.4%	8 NaN	9 NaN	2 NaN	0 NaN
Week 56 : Self-Care	16 57.1%	6 NaN	2 NaN	1 NaN	0 NaN
Week 56: Usual Activities	8 28.6%	9 NaN	5 NaN	3 NaN	0 NaN
Week 78 Anxiety/Depression	12 42.9%	6 NaN	3 NaN	2 NaN	1 NaN
Week 78 : Mobility	5 17.9%	8 NaN	8 NaN	2 NaN	1 NaN
Week 78 : Pain/Discomfort	4 14.3%	14 NaN	5 NaN	1 NaN	0 NaN
Week 78 : Self-Care	15 53.6%	6 NaN	2 NaN	1 NaN	0 NaN
Week 78 : Usual Activities	5 17.9%	12 NaN	6 NaN	1 NaN	0 NaN
Week 104 Anxiety/Depression	10 35.7%	7 NaN	4 NaN	0 NaN	1 NaN
Week 104 : Mobility	4 14.3%	5 NaN	10 NaN	2 NaN	1 NaN
Week 104 : Pain/Discomfort	5 17.9%	8 NaN	9 NaN	0 NaN	0 NaN
Week 104 : Self-Care	15 53.6%	4 NaN	1 NaN	2 NaN	0 NaN
Week 104 : Usual Activities	3 10.7%	13 NaN	4 NaN	2 NaN	0 NaN
Week 130 Anxiety/Depression	7 25%	8 NaN	3 NaN	4 NaN	0 NaN
Week 130 : Mobility	7 25%	4 NaN	8 NaN	3 NaN	0 NaN
Week 130 : Pain/Discomfort	7 25%	6 NaN	5 NaN	4 NaN	0 NaN
Week 130 : Self-Care	14 50%	5 NaN	1 NaN	2 NaN	0 NaN
Week 130 : Usual Activities	6 21.4%	8 NaN	6 NaN	1 NaN	1 NaN
Week 156 Anxiety/Depression	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
Week 156 : Mobility	1 3.6%	0 NaN	0 NaN	0 NaN	0 NaN
Week 156 : Pain/Discomfort	0 0%	0 NaN	1 NaN	0 NaN	0 NaN
Week 156 : Self-Care	1 3.6%	0 NaN	0 NaN	0 NaN	0 NaN
Week 156 : Usual Activities	0 0%	1 NaN	0 NaN	0 NaN	0 NaN
End of Study (Week 160) Anxiety/Depression	9 32.1%	6 NaN	4 NaN	1 NaN	1 NaN
End of Study (Week 160) : Mobility	3 10.7%	5 NaN	9 NaN	4 NaN	0 NaN
21End of Study (Week 160) : Pain/Discomfort	4 14.3%	7 NaN	8 NaN	2 NaN	0 NaN
End of Study (Week 160) : Self-Care	9 32.1%	8 NaN	3 NaN	1 NaN	0 NaN
End of Study (Week 160) : Usual Activities	5 17.9%	7 NaN	6 NaN	2 NaN	1 NaN

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom EQ VAS was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Baseline	65.29 (17.83)
Week 13	65.44 (22.68)
Week 26	62.70 (21.23)
Week 52	70.52 (21.27)
Week 78	64.88 (22.18)
Week 104	67.23 (21.75)
Week 130	72.18 (21.38)
Week 156	60.00 (NA)
End of Trial (Week 160)	60.48 (23.28)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom Neuro-Qol Fatigue was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Week 13	-8.39 (16.43)
Week 26	-9.33 (16.40)
Week 52	-10.88 (17.48)
Week 78	-6.79 (17.07)
Week 104	-8.27 (18.61)
Week 130	-6.77 (15.69)
Week 156	13.00 (NA)
End of Study (Week 21 up to Week 160)	-2.67 (17.38)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom PGA was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Excellent	1 3.6%
Fair	11 39.3%
Good	9 32.1%
Poor	5 17.9%
Very Good	2 7.1%
Excellent	0 0%
Fair	6 21.4%
Good	12 42.9%
Poor	2 7.1%
Very Good	6 21.4%
Excellent	1 3.6%
Fair	10 35.7%
Good	8 28.6%
Poor	3 10.7%
Very Good	5 17.9%
Excellent	0 0%
Fair	3 10.7%
Good	13 46.4%
Poor	4 14.3%
Very Good	5 17.9%
Excellent	0 0%
Fair	7 25%
Good	10 35.7%
Poor	4 14.3%
Very Good	3 10.7%
Excellent	0 0%
Fair	7 25%
Good	8 28.6%
Poor	2 7.1%
Very Good	5 17.9%
Excellent	1 3.6%
Fair	6 21.4%
Good	10 35.7%
Poor	4 14.3%
Very Good	1 3.6%
Excellent	0 0%
Fair	1 3.6%
Good	0 0%
Poor	0 0%
Very Good	0 0%
Excellent	0 0%
Fair	8 28.6%
Good	9 32.1%
Poor	3 10.7%
Very Good	1 3.6%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom Change From Baseline in Patient Global Assessment was measured.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Baseline	3.61 (0.99)
Week 13	3.15 (0.88)
Week 26	3.15 (0.88)
Week 52	3.24 (0.97)
Week 78	3.50 (0.93)
Week 104	3.27 (0.94)
Week 130	3.50 (1.01)
Week 156	4.00 (NA)
End of Trial (Week 160)	3.62 (0.80)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All individuals for whom Work Limitations was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Mental/Interpersonal: Baseline	67.59 (15.58)
Mental/Interpersonal: Week 13	71.33 (20.00)
Mental/Interpersonal: Week 26	72.00 (18.54)
Mental/Interpersonal: Week 52	75.06 (19.37)
Mental/Interpersonal: Week 78	70.62 (20.02)
Mental/Interpersonal: Week 104	68.57 (17.42)
Mental/Interpersonal: Week 130	66.11 (24.77)
Mental/Interpersonal: End of Trial (Week 160)	74.72 (19.66)
Output Task: Baseline	69.67 (20.99)
Output Task: Week 13	75.20 (21.89)
Output Task: Week 26	75.20 (18.16)
Output Task: Week 52	71.56 (18.05)
Output Task: Week 78	61.50 (20.28)
Output Task: Week 104	59.33 (25.85)
Output Task: Week 130	73.00 (22.50)
Output Task: End of Trial (Week 160)	71.00 (19.91)
Physical Task: Baseline	56.39 (23.37)
Physical Task Week 13	58.67 (17.37)
Physical Task Week 26	55.00 (11.57)
Physical Task Week 52	52.59 (14.32)
Physical Task Week 78	57.78 (11.55)
Physical Task Week 104	56.67 (25.53)
Physical Task Week 130	58.33 (23.03)
Physical Task: End of Trial (Week 160)	58.75 (23.03)
Time Management Baseline	61.60 (23.26)
Time Management Week 13	72.40 (21.54)
Time Management Week 26	68.00 (24.25)
Time Management Week 52	68.89 (25.83)
Time Management Week 78	72.89 (21.43)
Time Management Week 104	56.67 (27.76)
Time Management Week 130	57.71 (29.11)
Time Management End of Trial (Week 160)	68.57 (24.92)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom PhGA was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Baseline	3.32 (0.61)
Week 13	3.11 (0.80)
Week 26	3.00 (0.73)
Week 52	2.72 (0.84)
Week 78	3.25 (0.79)
Week 104	3.18 (0.85)
Week 130	3.18 (0.73)
Week 156	5.00 (NA)
End of Study (Week 160)	3.40 (0.60)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom PhGA was measured. Trial was terminated early.

Arm/Group Title	Excellent	Fair	Good	Poor	Very Good
Arm/Group Description	Number of participants the Physician rated current disease status as Excellent	Number of participants Physician rated current disease status as Fair	Number of participants Physician rated current disease status as Good	Number of participants Physician rated current disease status as Poor	Number of participants the Physician rated current disease status as Very Good
Measure Participants	28	28	28	28	28
Baseline	0 0%	8 NaN	18 NaN	1 NaN	1 NaN
Week 13	0 0%	7 NaN	13 NaN	1 NaN	6 NaN
Week 26	1 3.6%	6 NaN	16 NaN	0 NaN	4 NaN
Week 52	1 3.6%	2 NaN	12 NaN	1 NaN	9 NaN
Week 78	0 0%	8 NaN	11 NaN	1 NaN	4 NaN
Week 104	0 0%	4 NaN	12 NaN	2 NaN	4 NaN
Week 130	0 0%	5 NaN	13 NaN	1 NaN	3 NaN
Week 156	0 0%	0 NaN	0 NaN	1 NaN	0 NaN
End of Study (Week 160)	0 0%	6 NaN	13 NaN	1 NaN	0 NaN

10. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

All participants for which PMMSA was measured. Trial was terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Mild	11 39.3%
Moderate	5 17.9%
Not At All	8 28.6%
Severe	3 10.7%
Mild	5 17.9%
Moderate	16 57.1%
Not At All	1 3.6%
Severe	5 17.9%
Mild	4 14.3%
Moderate	6 21.4%
Not At All	16 57.1%
Severe	1 3.6%
Mild	6 21.4%
Moderate	12 42.9%
Not At All	5 17.9%
Severe	4 14.3%
Mild	12 42.9%
Moderate	10 35.7%
Not At All	1 3.6%
Severe	3 10.7%
Mild	2 7.1%
Moderate	18 64.3%
Not At All	0 0%
Severe	7 25%
Mild	11 39.3%
Moderate	2 7.1%
Not At All	11 39.3%
Severe	3 10.7%
Mild	6 21.4%
Moderate	13 46.4%
Not At All	0 0%
Severe	8 28.6%
Mild	5 17.9%
Moderate	13 46.4%
Not At All	0 0%
Severe	9 32.1%
Mild	8 28.6%
Moderate	9 32.1%
Not At All	6 21.4%
Severe	4 14.3%
Mild	6 21.4%
Moderate	8 28.6%
Not At All	11 39.3%
Severe	3 10.7%
Mild	11 39.3%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	7 25%
Mild	10 35.7%
Moderate	2 7.1%
Not At All	14 50%
Severe	2 7.1%
Mild	11 39.3%
Moderate	7 25%
Not At All	7 25%
Severe	3 10.7%
Mild	13 46.4%
Moderate	6 21.4%
Not At All	7 25%
Severe	2 7.1%
Mild	10 35.7%
Moderate	9 32.1%
Not At All	3 10.7%
Severe	6 21.4%
Mild	6 21.4%
Moderate	6 21.4%
Not At All	15 53.6%
Severe	1 3.6%
Mild	14 50%
Moderate	10 35.7%
Not At All	2 7.1%
Severe	2 7.1%
Mild	12 42.9%
Moderate	11 39.3%
Not At All	0 0%
Severe	5 17.9%
Mild	11 39.3%
Moderate	7 25%
Not At All	8 28.6%
Severe	2 7.1%
Mild	7 25%
Moderate	5 17.9%
Not At All	13 46.4%
Severe	2 7.1%
Mild	11 39.3%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	6 21.4%
Mild	13 46.4%
Moderate	1 3.6%
Not At All	12 42.9%
Severe	1 3.6%
Mild	11 39.3%
Moderate	7 25%
Not At All	7 25%
Severe	2 7.1%
Mild	13 46.4%
Moderate	4 14.3%
Not At All	7 25%
Severe	3 10.7%
Mild	10 35.7%
Moderate	11 39.3%
Not At All	1 3.6%
Severe	5 17.9%
Mild	7 25%
Moderate	3 10.7%
Not At All	14 50%
Severe	3 10.7%
Mild	15 53.6%
Moderate	8 28.6%
Not At All	1 3.6%
Severe	3 10.7%
Mild	12 42.9%
Moderate	10 35.7%
Not At All	0 0%
Severe	5 17.9%
Mild	6 21.4%
Moderate	9 32.1%
Not At All	7 25%
Severe	5 17.9%
Mild	10 35.7%
Moderate	2 7.1%
Not At All	10 35.7%
Severe	3 10.7%
Mild	10 35.7%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	5 17.9%
Mild	10 35.7%
Moderate	4 14.3%
Not At All	10 35.7%
Severe	1 3.6%
Mild	8 28.6%
Moderate	6 21.4%
Not At All	9 32.1%
Severe	2 7.1%
Mild	8 28.6%
Moderate	8 28.6%
Not At All	6 21.4%
Severe	3 10.7%
Mild	12 42.9%
Moderate	7 25%
Not At All	1 3.6%
Severe	5 17.9%
Mild	4 14.3%
Moderate	5 17.9%
Not At All	13 46.4%
Severe	3 10.7%
Mild	12 42.9%
Moderate	8 28.6%
Not At All	4 14.3%
Severe	1 3.6%
Mild	12 42.9%
Moderate	10 35.7%
Not At All	0 0%
Severe	3 10.7%
Mild	8 28.6%
Moderate	9 32.1%
Not At All	5 17.9%
Severe	3 10.7%
Mild	11 39.3%
Moderate	2 7.1%
Not At All	9 32.1%
Severe	2 7.1%
Mild	7 25%
Moderate	13 46.4%
Not At All	1 3.6%
Severe	3 10.7%
Mild	6 21.4%
Moderate	3 10.7%
Not At All	14 50%
Severe	1 3.6%
Mild	10 35.7%
Moderate	5 17.9%
Not At All	7 25%
Severe	2 7.1%
Mild	10 35.7%
Moderate	9 32.1%
Not At All	5 17.9%
Severe	0 0%
Mild	8 28.6%
Moderate	9 32.1%
Not At All	2 7.1%
Severe	5 17.9%
Mild	7 25%
Moderate	3 10.7%
Not At All	12 42.9%
Severe	2 7.1%
Mild	11 39.3%
Moderate	8 28.6%
Not At All	1 3.6%
Severe	4 14.3%
Mild	8 28.6%
Moderate	10 35.7%
Not At All	1 3.6%
Severe	5 17.9%
Mild	10 35.7%
Moderate	5 17.9%
Not At All	6 21.4%
Severe	3 10.7%
Mild	7 25%
Moderate	4 14.3%
Not At All	10 35.7%
Severe	1 3.6%
Mild	10 35.7%
Moderate	7 25%
Not At All	1 3.6%
Severe	4 14.3%
Mild	5 17.9%
Moderate	2 7.1%
Not At All	14 50%
Severe	1 3.6%
Mild	10 35.7%
Moderate	7 25%
Not At All	5 17.9%
Severe	0 0%
Mild	10 35.7%
Moderate	6 21.4%
Not At All	4 14.3%
Severe	1 3.6%
Mild	8 28.6%
Moderate	8 28.6%
Not At All	3 10.7%
Severe	3 10.7%
Mild	5 17.9%
Moderate	2 7.1%
Not At All	12 42.9%
Severe	3 10.7%
Mild	11 39.3%
Moderate	6 21.4%
Not At All	2 7.1%
Severe	3 10.7%
Mild	10 35.7%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	2 7.1%
Mild	7 25%
Moderate	5 17.9%
Not At All	5 17.9%
Severe	5 17.9%
Mild	8 28.6%
Moderate	1 3.6%
Not At All	9 32.1%
Severe	3 10.7%
Mild	8 28.6%
Moderate	7 25%
Not At All	1 3.6%
Severe	5 17.9%
Mild	8 28.6%
Moderate	2 7.1%
Not At All	11 39.3%
Severe	0 0%
Mild	7 25%
Moderate	4 14.3%
Not At All	7 25%
Severe	3 10.7%
Mild	9 32.1%
Moderate	7 25%
Not At All	4 14.3%
Severe	1 3.6%
Mild	8 28.6%
Moderate	8 28.6%
Not At All	1 3.6%
Severe	4 14.3%
Mild	7 25%
Moderate	3 10.7%
Not At All	11 39.3%
Severe	0 0%
Mild	9 32.1%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	2 7.1%
Mild	9 32.1%
Moderate	10 35.7%
Not At All	0 0%
Severe	2 7.1%
Mild	7 25%
Moderate	7 25%
Not At All	4 14.3%
Severe	3 10.7%
Mild	1 3.6%
Moderate	0 0%
Not At All	0 0%
Severe	0 0%
Mild	1 3.6%
Moderate	0 0%
Not At All	0 0%
Severe	0 0%
Mild	0 0%
Moderate	0 0%
Not At All	1 3.6%
Severe	0 0%
Mild	0 0%
Moderate	0 0%
Not At All	0 0%
Severe	1 3.6%
Mild	0 0%
Moderate	1 3.6%
Not At All	0 0%
Severe	0 0%
Mild	0 0%
Moderate	0 0%
Not At All	0 0%
Severe	1 3.6%
Mild	0 0%
Moderate	1 3.6%
Not At All	0 0%
Severe	0 0%
Mild	0 0%
Moderate	0 0%
Not At All	0 0%
Severe	1 3.6%
Mild	0 0%
Moderate	0 0%
Not At All	0 0%
Severe	1 3.6%
Mild	0 0%
Moderate	0 0%
Not At All	1 3.6%
Severe	0 0%
Mild	8 28.6%
Moderate	2 7.1%
Not At All	6 21.4%
Severe	4 14.3%
Mild	9 32.1%
Moderate	8 28.6%
Not At All	0 0%
Severe	4 14.3%
Mild	9 32.1%
Moderate	5 17.9%
Not At All	7 25%
Severe	0 0%
Mild	5 17.9%
Moderate	9 32.1%
Not At All	4 14.3%
Severe	3 10.7%
Mild	8 28.6%
Moderate	7 25%
Not At All	4 14.3%
Severe	2 7.1%
Mild	3 10.7%
Moderate	11 39.3%
Not At All	2 7.1%
Severe	5 17.9%
Mild	5 17.9%
Moderate	5 17.9%
Not At All	11 39.3%
Severe	0 0%
Mild	7 25%
Moderate	9 32.1%
Not At All	1 3.6%
Severe	4 14.3%
Mild	4 14.3%
Moderate	10 35.7%
Not At All	1 3.6%
Severe	6 21.4%
Mild	3 10.7%
Moderate	9 32.1%
Not At All	6 21.4%
Severe	3 10.7%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom PMMSA was measured. Study terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Week 13	-15.12 (29.33)
Week 26	-15.06 (29.72)
Week 52	-17.01 (25.36)
Week 78	-13.41 (31.05)
Week 104	-18.65 (30.15)
Week 130	-12.92 (31.12)
Week 156	25.00 (NA)
End of Trial (Week 160)	-8.33 (33.00)

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants for whom PMMSA was measured. Study terminated early.

Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
Measure Participants	28
Week 13	-14.20 (29.13)
Week 26	-14.10 (28.55)
Week 52	-17.36 (25.76)
Week 78	-14.49 (32.30)
Week 104	-20.63 (28.34)
Week 130	-15.00 (31.94)
Week 156	33.33 (NA)
End of Trial (Week 160)	-8.33 (31.30)

Adverse Events

Time Frame	Baseline through end of study for up to 260 weeks
Arm/Group Title	Elamipretide
Arm/Group Description	Open-label once daily subcutaneous injection of 40mg elamipretide elamipretide: 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.
All Cause Mortality
	Elamipretide
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Serious Adverse Events
	Elamipretide
	Affected / at Risk (%)	# Events
Total	8/28 (28.6%)
Cardiac disorders
Bradycardia	1/28 (3.6%)
Congenital, familial and genetic disorders
Hereditary optic atrophy	1/28 (3.6%)
Gastrointestinal disorders
Pancreatitis acute	1/28 (3.6%)
Dysphagia	1/28 (3.6%)
Intestinal obstruction	1/28 (3.6%)
Hepatobiliary disorders
Cholelithiasis	1/28 (3.6%)
Infections and infestations
Urosepsis	1/28 (3.6%)
Bacteraemia	1/28 (3.6%)
Urinary tract infection	1/28 (3.6%)
Cellulitis	1/28 (3.6%)
Pneumonia	1/28 (3.6%)
Injury, poisoning and procedural complications
Ankle fracture	1/28 (3.6%)
Tibia fracture	1/28 (3.6%)
Investigations
Troponin increased	1/28 (3.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer stage I	1/28 (3.6%)
Nervous system disorders
Hemiparesis	1/28 (3.6%)
Syncope	1/28 (3.6%)
Renal and urinary disorders
Renal colic	1/28 (3.6%)
Acute kidney injury	1/28 (3.6%)
Vascular disorders
Cerebrovascular accident	1/28 (3.6%)
Other (Not Including Serious) Adverse Events
	Elamipretide
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Cardiac disorders
Tachycardia	3/28 (10.7%)
Gastrointestinal disorders
Vomiting	5/28 (17.9%)
Abdominal distension	3/28 (10.7%)
Abdominal pain	3/28 (10.7%)
Abdominal pain upper	3/28 (10.7%)
Diarrhoea	3/28 (10.7%)
Abdominal discomfort	2/28 (7.1%)
Constipation	2/28 (7.1%)
Haemorrhoids	2/28 (7.1%)
Impaired gastric emptying	2/28 (7.1%)
Nausea	2/28 (7.1%)
Injection site pruritus	21/28 (75%)
General disorders
Injection site pruritus	18/28 (64.3%)
Injection site mass	13/28 (46.4%)
Injection site urticaria	13/28 (46.4%)
Injection site pain	10/28 (35.7%)
Injection site swelling	7/28 (25%)
Chest pain	6/28 (21.4%)
Fatigue	6/28 (21.4%)
Injection site bruising	4/28 (14.3%)
Injection site rash	4/28 (14.3%)
Pyrexia	3/28 (10.7%)
Chills	2/28 (7.1%)
Injection site haemorrhage	2/28 (7.1%)
Injection site induration	2/28 (7.1%)
Peripheral swelling	2/28 (7.1%)
Infections and infestations
Nasopharyngitis	8/28 (28.6%)
Gastroenteritis viral	6/28 (21.4%)
Urinary tract infection	4/28 (14.3%)
Sinusitis	4/28 (14.3%)
Upper respiratory tract infection	4/28 (14.3%)
Influenza	3/28 (10.7%)
Bronchitis	2/28 (7.1%)
Ear infection	2/28 (7.1%)
Fungal infection	2/28 (7.1%)
Hordeolum	2/28 (7.1%)
Pneumonia	2/28 (7.1%)
Postoperative wound infection	2/28 (7.1%)
Vaginal infection	2/28 (7.1%)
Ligament sprain	3/28 (10.7%)
Skin laceration	3/28 (10.7%)
Injury, poisoning and procedural complications
Fall	10/28 (35.7%)
Concussion	4/28 (14.3%)
Contusion	4/28 (14.3%)
Joint dislocation	2/28 (7.1%)
Muscle strain	2/28 (7.1%)
Thermal burn	2/28 (7.1%)
Investigations
Blood lactic acid increased	4/28 (14.3%)
Alanine aminotransferase increased	3/28 (10.7%)
Eosinophil count increased	3/28 (10.7%)
Weight increased	2/28 (7.1%)
Metabolism and nutrition disorders
Hypokalaemia	2/28 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/28 (14.3%)
Pain in extremity	4/28 (14.3%)
Back pain	3/28 (10.7%)
Muscle fatigue	2/28 (7.1%)
Muscular weakness	2/28 (7.1%)
Nervous system disorders
Headache	7/28 (25%)
Dizziness	3/28 (10.7%)
Hypoaesthesia	3/28 (10.7%)
Migraine	3/28 (10.7%)
Neuralgia	3/28 (10.7%)
Dizziness postural	2/28 (7.1%)
Dystonia	2/28 (7.1%)
Syncope	2/28 (7.1%)
Tremor	2/28 (7.1%)
Psychiatric disorders
Anxiety	3/28 (10.7%)
Depression	3/28 (10.7%)
Adjustment disorder with depressed mood	2/28 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/28 (10.7%)
Throat irritation	3/28 (10.7%)
Apnoea	3/28 (10.7%)
Nasal congestion	2/28 (7.1%)
Oropharyngeal pain	2/28 (7.1%)
Skin and subcutaneous tissue disorders
Rash	3/28 (10.7%)
Urticaria	3/28 (10.7%)
Acne	2/28 (7.1%)
Dermal cyst	2/28 (7.1%)
Pruritus	2/28 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.