MMPOWER-3: A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension

• Sponsor: Stealth BioTherapeutics Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03323749
• Collaborator: (none)
• Enrollment: 218
• Locations: 27
• Arms: 3
• Actual Duration (Months): 28.1
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a multicenter phase 3 randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the safety and efficacy of daily subcutaneous injections of elamipretide in subjects with primary mitochondrial myopathy. This will be followed by an open-label treatment extension.

Condition or Disease	Intervention/Treatment	Phase
Primary Mitochondrial Myopathy	Combination Product: elamipretide; Combination Product: placebo comparator; Combination Product: elamipretide open label treatment	Phase 3

Detailed Description

Part 11 is a 24-week, randomized, double-blind, parallel-group, placebo-controlled assessment of the efficacy and safety of single daily subcutaneous (SC) doses of 40 mg elamipretide (vs placebo) administered with the elamipretide delivery system as a treatment for subjects with primary mitochondrial myopathy (PMM). Part 2 was to assess the long-term safety and tolerability of single daily SC doses of 40 mg elamipretide administered with the elamipretide delivery system for up to 144 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Daily Subcutaneous Injections of Elamipretide in Subjects With Primary Mitochondrial Myopathy Followed by an Open-Label Treatment Extension
• Actual Study Start Date: Oct 9, 2017
• Actual Primary Completion Date: Feb 10, 2020
• Actual Study Completion Date: Feb 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Elamipretide 40 mg (0.5mL) elamipretide subcutaneous (SC) daily	Combination Product: elamipretide; 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system; Other Names: MTP-131
Placebo Comparator: Part 1: Placebo Placebo SC daily	Combination Product: placebo comparator; 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system; Other Names: Placebo
Experimental: Part 2: Elamipretide open label Elamepretide 40 mg (0.5 mL) SC daily	Combination Product: elamipretide open label treatment; 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system

Outcome Measures

Primary Outcome Measures

1. Six-minute Walk Test (6MWT) [Baseline to 24 weeks]

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

2. Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) [Baseline to 24 weeks]

   Change from Baseline in Total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) by visit. Each individual item score ranges from 1 (none) to 4 (severe). The total fatigue score ranges from 4-16. Lower values represent a better outcome. The total fatigue score is the sum of question 1 through question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.

Secondary Outcome Measures

1. Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA). [Baseline to 24 weeks]

   Change from baseline in Fatigue During Activities. Fatigue During Activities is the sum of question 2 (tiredness during activities) and question 4 (muscle weakness during activities.) The four response options are: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Raw scores for each subject range from 2-8. A lower score means a better outcome, with less fatigue. A higher score means a worse outcome, with more fatigue.

2. Neuro-QoL Fatigue Activities of Daily Living [Baseline to 24 weeks]

   Change From Baseline in Neuro-QoL Fatigue Activities of Daily Living by Visit. Each individual item score ranges from 1-5. Total raw score for the entire item bank ranges from 19-95. Raw scores will be calibrated using Item Response Theory Model. Lower values represent a better outcome. Individual items will be summed to calculate total scores.

3. Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment [Baseline to 24 weeks]

   The item score rangers from 1 (none) to 4 (severe). Lower values represent a better outcome. The most bothersome score is the average of the identified most bothersome symptom of the Primary Mitochondrial Myopathy Symptom Assessment by each subject.

4. Neuro-QoL Fatigue Short Form Score [24 Weeks]

   Change From Baseline in Neuro-QoL Fatigue - Short Form: Total T-Scores by Visit. The Neuro-QoL Fatigue Short Form is comprised of the sum of the first 8 questions of the Neuro-QoL Item Bank v1.0 - Fatigue. Each question is scored as following: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always. The questions include: I felt exhausted, I felt that I had no energy, I felt fatigued, I was too tired to do my household chores, I was too tired to leave the house, I was frustrated by being too tired to do the things I wanted to do, I felt tired, and I had to limit my social activity because I was tired. T-scores are calculated from the short form scoring table provided by the instrument authors (Neuro-QoL User Manual, 2015). T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Change from baseline: Negative numbers mean less fatigue, better outcome, positive score means more fatigue, worse outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

PART 1:

Inclusion Criteria:

• Willing and able to provide a signed informed consent form prior to participation in any trial-related procedures

• Agrees to adhere to the trial requirements for the length of the trial, including the use of the elamipretide delivery system

• Subject is ≥ 16 and ≤ 80 years of age

• Diagnosed with PMM in the opinion of the investigator and confirmed by an Adjudication Committee

• Woman of childbearing potential must agree to use a highly effective method of birth control

Exclusion Criteria:

• Subject has myopathic signs and or/symptoms due to a neuropathic process or gait problem that would interfere with the 6 minute walk test (6MWT), in the opinion of the Investigator

• Female who are pregnant, planning to become pregnant, or breastfeeding/lactating

• At Screening, the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2

• Subject has undergone an in-patient hospitalization within the 30 days prior to the Baseline Visit or has a planned hospitalization or a surgical procedure during the trial.

• Subject has clinically significant cardiac disease or prior interventional procedure and/or respiratory disease (medical history or current clinical findings) within 3 months of the Baseline Visit, in the opinion of the Investigator.

• Subject has QTc elongation (using the correction factor utilized at the clinical site) defined as a QTc >450 msec in male subjects and >480 msec in female subjects.

• ECG evidence of acute ischemia, atrial fibrillation, or active conduction system abnormalities with the exception of any of the following:

1. First degree Atrioventricular bock (AV-block)

2. Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)

3. Right bundle branch block

• Subject has severe vision impairment that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements

• Subject has a seizure disorder that, in the opinion of the Investigator, may interfere with their ability to complete all trial requirements.

• Active malignancy or any other cancer from which the subject has been disease-free for < 2 years.

• Subject has a solid organ transplant and/or is currently receiving treatment with therapy for immunosuppression, in the opinion of the Investigator.

• Subject has been previously diagnosed with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.

• Subject has a history of a systemic eosinophilic illness and/or an eosinophil count

1,000 cells x10^6/L at the Screening Visit.

• Subject is currently participating or has participated in an interventional clinical trial (i.e.,investigational product or device, stem cell therapy, gene therapy) within 30 days of the Baseline Visit; or is currently enrolled in a non-interventional clinical trial (except for SPIMM-300) at the Baseline Visit which, in the opinion of the Investigator, may be potentially confounding with results of the current trial (e.g., exercise therapy trial).

• Subject has previously received elamipretide (MTP-131), for any reason.

• Subject has a history of active substance abuse during the year before the Baseline Visit, in the opinion of the Investigator.

• 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.

PART 2:

Continuation Criteria:

• Subjects must continue to be able and willing to adhere to the trial requirements.

• Subject is appropriate to continue in Part 2 (i.e. subject was compliant in Part 1), in the opinion of the Investigator.

• Subject has not had a serious adverse event (SAE)/serious adverse device effect (SADE) attributed to the elamipretide delivery system.

• Subject has not permanently discontinued the elamipretide delivery system.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego	La Jolla	California	United States	92093
2	Stanford University	Palo Alto	California	United States	94304
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Rare Disease Research, LLC	Atlanta	Georgia	United States	30318
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Columbia University Medical Center	New York	New York	United States	10032
7	Akron Children's Hospital	Akron	Ohio	United States	44308
8	Cleveland Clinical Neurological Institute	Cleveland	Ohio	United States	44195
9	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
10	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
11	Baylor College of Medicine/Texas Children's Hospital	Houston	Texas	United States	77030
12	University of Texas Health Science Center	Houston	Texas	United States	77030
13	Seattle Children's Hospital	Seattle	Washington	United States	98105
14	Adult Metabolic Diseases Clinic	Vancouver	British Colombia	Canada
15	McMaster University Medical Center	Hamilton	Ontario	Canada
16	Copenhagen Neuromuscular Center	Copenhagen		Denmark	DK-2100
17	University Hospital of Bonn	Bonn		Germany	53105
18	Klinikum der Universität München, Friedrich-Baur Institute	Munich		Germany	80336
19	Institute of Genomic Medicine and Rare Disorders	Budapest		Hungary	1083
20	IRCCS Institute of Neorological Sciences of Bologna, Bellaria Hospital	Bologna		Italy	40139
21	Azienda Ospedaliero Universitaria Policlinico G. Martino	Messina		Italy	98125
22	Istituto Nazionale Neurologico Carlo Besta	Milan		Italy	20133
23	Dipartimento Ambientale di Neuroscienze	Pisa		Italy	56126
24	Ospedale Pediatrico Bambin Gesù	Rome		Italy	00165
25	Istituto di Neurologia, Fondazione Policlinico Universitario A. Gemelli	Rome		Italy	00168
26	MRC Centre for Neuromuscular Diseases	London		United Kingdom
27	Royal Victoria Infirmary	Newcastle Upon Tyne		United Kingdom

Sponsors and Collaborators

• Stealth BioTherapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 15, 2018
• Statistical Analysis Plan - Nov 29, 2019

More Information

Publications

None provided.

• Responsible Party: Stealth BioTherapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03323749
• Other Study ID Numbers: SPIMM-301
• First Posted: Oct 27, 2017
• Last Update Posted: Jan 24, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Stealth BioTherapeutics Inc.: Myopathy; PMD; Primary Mitochondrial Disease; MTP-131; elamipretide
• Additional relevant MeSH terms: Muscular Diseases; Mitochondrial Myopathies

Study Results

Participant Flow

Arm/Group Title	Double-Blind Elamipretide, Then Open Label Elamepretide	Double-Blind Placebo Then Open-Label Elamepretide
Arm/Group Description	40 mg (0.5mL) elamipretide subcutaneous (SC) daily elamipretide: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system, then elamipretide open-label treatment: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system	Placebo SC daily Double-blind period: placebo comparator: Placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system. Open-label period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system.
Period Title: Double-blind Period
STARTED	109	109
COMPLETED	102	103
NOT COMPLETED	7	6
Period Title: Double-blind Period
STARTED	93	103
COMPLETED	0	0
NOT COMPLETED	93	103

Baseline Characteristics

Arm/Group Title	Elamipretide	Placebo	Total
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system, then Open-label Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks, then Open-label Period: Elamipretide: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system	Total of all reporting groups
Overall Participants	109	109	218
Age, Customized (years) [Mean (Standard Deviation) ]
Years, Double-blind	45.5 (15.72)	44.3 (14.34)	44.9 (15.02)
Years, Open-label	45.7 (15.97)	45.0 (14.25)	45.3 (15.05)
Sex: Female, Male (Count of Participants)
Female	67 61.5%	73 67%	140 64.2%
Male	42 38.5%	36 33%	78 35.8%
Female	56 51.4%	67 61.5%	123 56.4%
Male	37 33.9%	36 33%	73 33.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 10.1%	10 9.2%	21 9.6%
Not Hispanic or Latino	95 87.2%	96 88.1%	191 87.6%
Unknown or Not Reported	3 2.8%	3 2.8%	6 2.8%
Hispanic or Latino	8 7.3%	10 9.2%	18 8.3%
Not Hispanic or Latino	82 75.2%	91 83.5%	173 79.4%
Unknown or Not Reported	3 2.8%	2 1.8%	5 2.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.9%	0 0%	1 0.5%
Asian	2 1.8%	5 4.6%	7 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.9%	0 0%	1 0.5%
White	103 94.5%	100 91.7%	203 93.1%
More than one race	2 1.8%	1 0.9%	3 1.4%
Unknown or Not Reported	0 0%	3 2.8%	3 1.4%
American Indian or Alaska Native	1 0.9%	0 0%	1 0.5%
Asian	0 0%	4 3.7%	4 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.9%	0 0%	1 0.5%
White	89 81.7%	95 87.2%	184 84.4%
More than one race	2 1.8%	1 0.9%	3 1.4%
Unknown or Not Reported	0 0%	3 2.8%	3 1.4%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Double-blind	64.81 (20.287)	67.24 (17.336)	66.02 (18.865)
Open-label	65.66 (20.867)	68.01 (17.237)	66.89 (19.033)

Outcome Measures

1. Primary Outcome

Title	Six-minute Walk Test (6MWT)
Description	Change From Baseline in Distance Walked (meters) on the Six-Minute Walk Test by Visit
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

All participants for whom 6MWT was measured

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks
Measure Participants	109	109
Week 4	16.243 (42.0071)	7.811 (39.5737)
Week 12	18.286 (47.7766)	8.801 (52.1093)
Week 24	15.330 (61.4860)	17.386 (51.6956)

2. Primary Outcome

Title	Total Fatigue Score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA)
Description	Change from Baseline in Total fatigue score on the on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) by visit. Each individual item score ranges from 1 (none) to 4 (severe). The total fatigue score ranges from 4-16. Lower values represent a better outcome. The total fatigue score is the sum of question 1 through question 4 on the Primary Mitochondrial Myopathy Symptom Assessment.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

All participants for whom Total Fatigue Score (Q1 to Q4) Based on PMMSA by Visit was measured

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system, then Open-label Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks, then Open-label Period: Elamipretide: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system
Measure Participants	109	109
Week 4	-1.01 (1.714)	-1.08 (1.865)
Week 12	-1.08 (1.775)	-1.26 (2.259)
Week 24	-1.18 (2.132)	-1.09 (2.443)

3. Secondary Outcome

Title	Fatigue During Activities Score on the Primary Mitochondrial Disease Symptom Assessment (PMMSA).
Description	Change from baseline in Fatigue During Activities. Fatigue During Activities is the sum of question 2 (tiredness during activities) and question 4 (muscle weakness during activities.) The four response options are: 1=Not at all, 2=Mild, 3=Moderate, and 4=Severe. Raw scores for each subject range from 2-8. A lower score means a better outcome, with less fatigue. A higher score means a worse outcome, with more fatigue.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

All participants for whom Fatigue During Activities was measured.

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks
Measure Participants	109	109
Week 4	-0.48 (0.890)	-0.60 (0.998)
Week 12	-0.57 (0.923)	-0.67 (1.199)
Week 24	-0.64 (1.151)	-0.59 (1.360)

4. Secondary Outcome

Title	Neuro-QoL Fatigue Activities of Daily Living
Description	Change From Baseline in Neuro-QoL Fatigue Activities of Daily Living by Visit. Each individual item score ranges from 1-5. Total raw score for the entire item bank ranges from 19-95. Raw scores will be calibrated using Item Response Theory Model. Lower values represent a better outcome. Individual items will be summed to calculate total scores.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

All participants for whom Change From Baseline in Neuro-QoL Fatigue Activities of Daily Living by Visit was measured.

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks
Measure Participants	109	109
Week 4	-2.5 (5.33)	-2.7 (5.31)
Week 12	-2.9 (6.00)	-2.9 (5.13)
Week 24	-2.7 (6.06)	-2.1 (5.39)

5. Secondary Outcome

Title	Change From Baseline in the Most Bothersome Symptom Score on the Primary Mitochondrial Myopathy Symptoms Assessment
Description	The item score rangers from 1 (none) to 4 (severe). Lower values represent a better outcome. The most bothersome score is the average of the identified most bothersome symptom of the Primary Mitochondrial Myopathy Symptom Assessment by each subject.
Time Frame	Baseline to 24 weeks

Outcome Measure Data

Analysis Population Description

All participants for whom Most Bothersome Symptom Score (PMMSA) by Visit was measured.

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks
Measure Participants	109	109
Week 4	-0.21 (0.492)	-0.24 (0.535)
Week 12	-0.24 (0.535)	-0.34 (0.656)
Week 24	-0.25 (0.618)	-0.30 (0.713)

6. Secondary Outcome

Title	Neuro-QoL Fatigue Short Form Score
Description	Change From Baseline in Neuro-QoL Fatigue - Short Form: Total T-Scores by Visit. The Neuro-QoL Fatigue Short Form is comprised of the sum of the first 8 questions of the Neuro-QoL Item Bank v1.0 - Fatigue. Each question is scored as following: 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always. The questions include: I felt exhausted, I felt that I had no energy, I felt fatigued, I was too tired to do my household chores, I was too tired to leave the house, I was frustrated by being too tired to do the things I wanted to do, I felt tired, and I had to limit my social activity because I was tired. T-scores are calculated from the short form scoring table provided by the instrument authors (Neuro-QoL User Manual, 2015). T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Change from baseline: Negative numbers mean less fatigue, better outcome, positive score means more fatigue, worse outcome.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

All participants for whom Neuro-QoL Fatigue Short Form Score T-scores were measured.

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Double-blind Period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system	Double-Blind Period: Placebo comparator: 40 mg of placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks
Measure Participants	109	109
Week 4	-3.37 (5.077)	-2.89 (5.915)
Week 12	-3.43 (5.681)	-3.60 (5.614)
Week 24	-2.68 (5.769)	-2.61 (5.773)

Adverse Events

Time Frame	Double-blind period: 24 weeks and continued with Open-label period: up to 144 weeks.
Arm/Group Title	Double-Blind Elamipretide		Double-Blind Placebo		Open-Label Elamipretide		Open-Label Placebo
Arm/Group Description	Double-blind period: elamipretide: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system, then elamipretide open-label treatment: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system		Placebo SC daily Double-blind period: placebo comparator: Placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system. Open-label period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system.		Double blind period: elamipretide: 40mg (0.5mL) of elamipretide administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system, then elamipretide open-label treatment: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system		Double-blind period: placebo comparator: Placebo administered as once daily 0.5 mL subcutaneous injections for 24 weeks using the elamipretide delivery system. Open-label period: 40 mg of elamipretide administered as once daily 0.5 mL subcutaneous injections for up to 144 weeks using the elamipretide delivery system.
All Cause Mortality
	Double-Blind Elamipretide		Double-Blind Placebo		Open-Label Elamipretide		Open-Label Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/109 (0%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Serious Adverse Events
	Double-Blind Elamipretide		Double-Blind Placebo		Open-Label Elamipretide		Open-Label Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/109 (4.6%)		3/109 (2.8%)		12/93 (12.9%)		9/103 (8.7%)
Cardiac disorders
Acute myocardial infarction	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Coronary artery dissection	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Atrioventricular block complete	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Congenital, familial and genetic disorders
MELAS syndrome	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Ear and labyrinth disorders
Vertigo	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Gastrointestinal disorders
Gastroenteritis	0/109 (0%)		1/109 (0.9%)		0/93 (0%)		0/103 (0%)
Intestinal pseudo-obstruction	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Duodenal ulcer haemorrhage	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
General disorders
Chest pain	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Hepatobiliary disorders
Cholelithiasis	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Infections and infestations
Cellulitis	1/109 (0.9%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Diverticulitis	1/109 (0.9%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Viral sinusitis	1/109 (0.9%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Sinusitis	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Injury, poisoning and procedural complications
Humerus fracture	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Vaginal laceration	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Metabolism and nutrition disorders
Dehydration	1/109 (0.9%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Lactic Acidosis	1/109 (0.9%)		0/109 (0%)		0/93 (0%)		0/103 (0%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	0/109 (0%)		1/109 (0.9%)		0/93 (0%)		1/103 (1%)
Intervertebral disc disorder	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Papillary thyroid cancer	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Nervous system disorders
Hypoaesthesia	0/109 (0%)		1/109 (0.9%)		0/93 (0%)		0/103 (0%)
Psychogenic seizure	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Cerebrovascular accident	0/109 (0%)		0/109 (0%)		0/93 (0%)		2/103 (1.9%)
Spinal cord compression	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Hemiplegia	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Psychiatric disorders
Suicidal Ideation	1/109 (0.9%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Renal and urinary disorders
Urinary retention	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Asthma	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Skin and subcutaneous tissue disorders
Urticaria	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Vascular disorders
Hypertension	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		0/103 (0%)
Labile blood pressure	0/109 (0%)		0/109 (0%)		0/93 (0%)		1/103 (1%)
Other (Not Including Serious) Adverse Events
	Double-Blind Elamipretide		Double-Blind Placebo		Open-Label Elamipretide		Open-Label Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/109 (98.2%)		83/109 (76.1%)		88/93 (94.6%)		102/103 (99%)
Blood and lymphatic system disorders
Eosinophilia	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		9/103 (8.7%)
Gastrointestinal disorders
Nausea	5/109 (4.6%)		8/109 (7.3%)		4/93 (4.3%)		2/103 (1.9%)
Diarrhoea	3/109 (2.8%)		9/109 (8.3%)		3/93 (3.2%)		6/103 (5.8%)
Constipation	0/109 (0%)		0/109 (0%)		3/93 (3.2%)		2/103 (1.9%)
Abdominal Pain	0/109 (0%)		0/109 (0%)		3/93 (3.2%)		1/103 (1%)
General disorders
Injection site erythema	94/109 (86.2%)		31/109 (28.4%)		66/93 (71%)		87/103 (84.5%)
Injection site pruritus	82/109 (75.2%)		10/109 (9.2%)		57/93 (61.3%)		81/103 (78.6%)
Injection site pain	43/109 (39.4%)		20/109 (18.3%)		32/93 (34.4%)		37/103 (35.9%)
Injection site swelling	42/109 (38.5%)		7/109 (6.4%)		29/93 (31.2%)		20/103 (19.4%)
Injection site induration	31/109 (28.4%)		6/109 (5.5%)		25/93 (26.9%)		41/103 (39.8%)
injection site bruising	9/109 (8.3%)		18/109 (16.5%)		5/93 (5.4%)		15/103 (14.6%)
injection site haemorrhage	7/109 (6.4%)		10/109 (9.2%)		2/93 (2.2%)		8/103 (7.8%)
injection site urticaria	14/109 (12.8%)		0/109 (0%)		12/93 (12.9%)		8/103 (7.8%)
injection site nodule	11/109 (10.1%)		2/109 (1.8%)		8/93 (8.6%)		8/103 (7.8%)
injection site mass	9/109 (8.3%)		2/109 (1.8%)		4/93 (4.3%)		4/103 (3.9%)
Fatigue	4/109 (3.7%)		4/109 (3.7%)		4/93 (4.3%)		4/103 (3.9%)
injection site haematoma	0/109 (0%)		7/109 (6.4%)		0/93 (0%)		0/103 (0%)
Pyrexia	2/109 (1.8%)		3/109 (2.8%)		0/93 (0%)		0/103 (0%)
Asthenia	0/109 (0%)		0/109 (0%)		3/93 (3.2%)		2/103 (1.9%)
Injection site injury	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		4/103 (3.9%)
Infections and infestations
Upper respiratory tract Infection	7/109 (6.4%)		7/109 (6.4%)		7/93 (7.5%)		7/103 (6.8%)
Nasopharyngitis	8/109 (7.3%)		2/109 (1.8%)		6/93 (6.5%)		2/103 (1.9%)
Sinusitis	2/109 (1.8%)		3/109 (2.8%)		2/93 (2.2%)		4/103 (3.9%)
Influenza	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Pneumonia	1/109 (0.9%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Urinary Tract Infection	0/109 (0%)		0/109 (0%)		4/93 (4.3%)		0/103 (0%)
Injury, poisoning and procedural complications
Fall	6/109 (5.5%)		3/109 (2.8%)		8/93 (8.6%)		7/103 (6.8%)
Skin Abrasion	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		3/103 (2.9%)
Investigations
Eosinophil count increased	7/109 (6.4%)		0/109 (0%)		7/93 (7.5%)		7/103 (6.8%)
Blood creatine phosphokinase increased	0/109 (0%)		0/109 (0%)		4/93 (4.3%)		1/103 (1%)
Weight Decreased	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		3/103 (2.9%)
Blood glucose increased	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Blood lactic acid increased	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/109 (0.9%)		5/109 (4.6%)		2/93 (2.2%)		5/103 (4.9%)
Back Pain	0/109 (0%)		0/109 (0%)		4/93 (4.3%)		2/103 (1.9%)
Arthralgia	0/109 (0%)		0/109 (0%)		3/93 (3.2%)		2/103 (1.9%)
Muscle Spasms	0/109 (0%)		0/109 (0%)		4/93 (4.3%)		0/103 (0%)
Muscular Weakness	0/109 (0%)		0/109 (0%)		3/93 (3.2%)		1/103 (1%)
Nervous system disorders
Headache	8/109 (7.3%)		4/109 (3.7%)		5/93 (5.4%)		6/103 (5.8%)
Dizziness	6/109 (5.5%)		3/109 (2.8%)		1/93 (1.1%)		3/103 (2.9%)
Hypoaesthesia	0/109 (0%)		0/109 (0%)		1/93 (1.1%)		3/103 (2.9%)
Migraine	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/109 (3.7%)		1/109 (0.9%)		3/93 (3.2%)		3/103 (2.9%)
Skin and subcutaneous tissue disorders
Rash	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		2/103 (1.9%)
Vascular disorders
Hypertension	0/109 (0%)		0/109 (0%)		2/93 (2.2%)		3/103 (2.9%)

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.