A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly (MOTION)

• ClinicalTrials.gov Identifier: NCT02245620
• Recruitment Status: Completed
• First Posted: September 19, 2014
• Results First Posted: June 23, 2020
• Last Update Posted: June 23, 2020
• Sponsor: Stealth BioTherapeutics Inc.
• Information provided by (Responsible Party): Stealth BioTherapeutics Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Skeletal Muscle Mitochondrial Dysfunction in the Elderly
• Interventions: Drug: Elamipretide; Drug: Placebo
• Enrollment: 41

Participant Flow

Recruitment Details
Pre-assignment Details	2 subjects discontinued prematurely as per Investigator's discretion. These 2 subjects (Subject 001019 [Elamipretide group] and Subject 001063 [Placebo group]) were discontinued after randomization but prior to receiving study treatment; both were not treated due to their pre-infusion sodium levels meeting Exclusion Criteria 6.

Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Elamipretide administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Period Title: Overall Study
Started	20	21
Completed	19	20
Not Completed	1	1
Reason Not Completed
Physician Decision	1	1

Baseline Characteristics

Arm/Group Title		MTP-131 (Bendavia™)	Placebo	Total
Arm/Group Description		MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours	Total of all reporting groups
Overall Number of Baseline Participants		19	20	39
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	19 participants	20 participants	39 participants
		67.9 (3.35)	69.0 (3.96)	68.5 (3.67)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	20 participants	39 participants
	Female	11 57.9%	7 35.0%	18 46.2%
	Male	8 42.1%	13 65.0%	21 53.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	20 participants	39 participants
	Hispanic or Latino	1 5.3%	0 0.0%	1 2.6%
	Not Hispanic or Latino	18 94.7%	19 95.0%	37 94.9%
	Unknown or Not Reported	0 0.0%	1 5.0%	1 2.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	20 participants	39 participants
	American Indian or Alaska Native	1 5.3%	0 0.0%	1 2.6%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	18 94.7%	20 100.0%	38 97.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	19 participants	20 participants	39 participants
		19	20	39
Body Mass index; Mean (Standard Deviation); Unit of measure: Kg/m²
	Number Analyzed	19 participants	20 participants	39 participants
		26.5 (4.27)	26.1 (2.82)	26.3 (3.56)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in ATPmax (Maximal ATP Synthetic Rate)
Description	Maximal ATP synthetic rate (phosphorylation capacity per unit muscle volume) as determined by a muscle fatigue test.
Time Frame	From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

Outcome Measure Data

Analysis Population Description

All participants for whom Maximal ATP synthetic rate was measured at baseline and Day 1 Hour 2, and Day 7

Arm/Group Title		MTP-131 (Bendavia™)	Placebo
Arm/Group Description:		MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Overall Number of Participants Analyzed		19	20
Mean (Standard Deviation); Unit of Measure: mM/sec
Day 1 Hour 2	Number Analyzed	18 participants	19 participants
		0.17 (0.196)	0.12 (0.244)
Day 7	Number Analyzed	19 participants	20 participants
		0.09 (0.142)	0.06 (0.172)

2. Secondary Outcome

Title	Mean Change From Baseline in Phosphate/Oxygen (P/O) Ratio
Description	As a measure of mitochondrial hand skeletal muscle energetics, mitochondrial coupling, or Phosphate/Oxygen ratio (P/O) was assessed at Baseline, Day 1 Hour 2, and Day 7.
Time Frame	From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

Outcome Measure Data

Analysis Population Description

All participants for whom Phosphate/Oxygen (P/O) ratio was measured at baseline and Day 1 Hour 2, and Day 7

Arm/Group Title		MTP-131 (Bendavia™)	Placebo
Arm/Group Description:		MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Overall Number of Participants Analyzed		19	20
Mean (Standard Deviation); Unit of Measure: ratio of phosphate to oxygen
Day 1 Hour 2	Number Analyzed	18 participants	20 participants
		0.25 (0.679)	0.26 (0.693)
Day 7	Number Analyzed	19 participants	20 participants
		0.32 (0.473)	0.51 (0.788)

3. Secondary Outcome

Title	Mean Change From Baseline in Nicotine Adenine Dinucleotide (NAD)
Description	[Not Specified]
Time Frame	From Baseline, Day 1 Hour 2 (2 hours after the start of infusion, or end of infusion) and Day 7

Outcome Measure Data

Analysis Population Description

All participants for whom Nicotine Adenine Dinucleotide (NAD) was measured.

Arm/Group Title		MTP-131 (Bendavia™)	Placebo
Arm/Group Description:		MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Overall Number of Participants Analyzed		19	20
Mean (Standard Deviation); Unit of Measure: millimolar
Day 1 Hour 2	Number Analyzed	18 participants	20 participants
		0.04 (0.169)	0.01 (0.213)
Day 7	Number Analyzed	19 participants	20 participants
		0.11 (0.215)	0.09 (0.263)

4. Secondary Outcome

Title	Mean Change From Baseline in Muscle Force-Time-Integral (FTI)
Description	Muscle Force-Time-Integral was measured as mean change from baseline at Day 1 Hour 2, Day 3, and Day 7.
Time Frame	From Baseline to Day 1 Hour 2, Day 3, and Day 7

Outcome Measure Data

Analysis Population Description

All participants for whom Muscle Force-Time-Integral (FTI) was measured.

Arm/Group Title		MTP-131 (Bendavia™)	Placebo
Arm/Group Description:		MTP-131 (Bendavia™) administered as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours.	Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
Overall Number of Participants Analyzed		19	20
Mean (Standard Deviation); Unit of Measure: Newton/second
Day 1 Hour 2	Number Analyzed	19 participants	20 participants
		0.43 (0.882)	0.10 (0.728)
Day 3	Number Analyzed	18 participants	20 participants
		0.46 (1.036)	0.24 (0.948)
Day 7	Number Analyzed	19 participants	20 participants
		0.83 (1.485)	0.44 (1.114)

Adverse Events

Time Frame	36 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Elamipretide	Placebo
Arm/Group Description	Elamipretide given as an intravenous infusion of 0.25 mg/kg/hr at a rate of 60 mL/hr for 2 hours. Elamipretide: Elamipretide 0.25 mg/kg/hour administered as an intravenous infusion at the rate of 60 mL/hour for 2 hours	Placebo (lyophilized excipients without elamipretide) given as an intravenous infusion at a rate of 60 mL/hr for 2 hours. Placebo: Placebo administered as intravenous infusion at a rate of 60 mL/hour for 2 hours
All-Cause Mortality
	Elamipretide	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	0/20 (0.00%)
Serious Adverse Events
	Elamipretide	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/19 (0.00%)	0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Elamipretide	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/19 (15.79%)	2/20 (10.00%)
Cardiac disorders
Palpitations † 2	1/19 (5.26%)	0/20 (0.00%)
Gastrointestinal disorders
Nausea † 1	0/19 (0.00%)	1/20 (5.00%)
General disorders
Vessel puncture site bruise † 2	0/19 (0.00%)	1/20 (5.00%)
Infections and infestations
Herpes zoster † 2	1/19 (5.26%)	0/20 (0.00%)
Nervous system disorders
Dizziness † 1	1/19 (5.26%)	0/20 (0.00%)
Headache † 2	0/19 (0.00%)	1/20 (5.00%)
Respiratory, thoracic and mediastinal disorders
Sinus congestion † 2	1/19 (5.26%)	0/20 (0.00%)
1 Term from vocabulary, MedDRA 19.0; 2 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc
• Phone: 1-617-600-6888
• EMail: jim.carr@stealthbt.com

• Responsible Party: Stealth BioTherapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02245620
• Other Study ID Numbers: SPITM-201
• First Submitted: September 17, 2014
• First Posted: September 19, 2014
• Results First Submitted: May 31, 2020
• Results First Posted: June 23, 2020
• Last Update Posted: June 23, 2020