A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome (TAZPOWER)

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Crossover Trial to Evaluate the Safety and Efficacy of Subcutaneous Injections of Elamipretide in Subjects With Genetically Confirmed Barth Syndrome Followed by Open-Label Treatment

A randomized, double-blind cross over trial to evaluate the safety, efficacy, and tolerability of elamipretide in subjects with Barth syndrome.

Study Overview

• Status: Completed
• Conditions: Barth Syndrome
• Intervention / Treatment: Drug: Elamipretide; Drug: Placebo

Detailed Description

A phase 2 randomized, double-blind, placebo-controlled crossover trial to evaluate the safety, tolerability, and efficacy of subcutaneous injections of elamipretide in subjects with genetically confirmed Barth syndrome followed by open-label treatment extension. Part 1 was a randomized, double-blind, placebo-controlled, crossover trial to assess safety, tolerability, and efficacy single daily subcutaneous (SC) doses of 40 mg elamipretide administered for 12 weeks in subjects with Barth syndrome. Part 2: This was an open-label extension trial to assess the long-term safety, tolerability, and longitudinal trends in efficacy single daily SC doses of 40 mg elamipretide for up to 192 weeks.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetically confirmed Barth Syndrome
• Male aged 12 and above

• At the screening visit, eGFR must meet the following:

  1. Body weight >30 kg AND eGFR ≥ 90mL/min at screening
  2. Body weight >40kg AND eGFR ≥60 but <90mL/min/ 1.73m² at screening
• Ambulatory and impaired during the baseline 6MWT
• On stable medication for 30 days prior to the baseline visit

Exclusion Criteria:

• Participated in another interventional clinical trial within 30 days of or is currently enrolled in a non-interventional clinical trial at the baseline visit potentially confounding with this trial
• Prior or current medical condition that would prevent the subject from safely participating in the trial
• Undergone any inpatient hospitalizations within 30 days of the baseline visit
• Is undergoing an apparent pubertal growth spurt
• Has uncontrolled hypertension
• History of substance abused within the year before the baseline visit or is likely to be uncompliant
• History of heart transplantation or current placement on the waiting list for a heart transplant
• For subjects with an ICD: known occurrence of ICD discharge in the 3 months prior to the baseline visit
• For subjects without an ICD: expected to undergo an implantation of an ICD during the conduct of the study
• Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or has received prior radiation therapy to the chest
• Recipient of stem cell or gene therapy or is currently being treated by a therapeutic investigational device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elamipretide, then Placebo; Experimental Part 1: 12 weeks of single daily SC doses of 40 mg elamipretide in Treatment Period 1 followed by 12 weeks of treatment with placebo in Treatment Period 2 (separated by a 4 week washout period). Experimental Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks	Drug: Elamipretide; 40 mg daily subcutaneous injection for 12 weeks; Other Names: MTP-131; Drug: Placebo; daily subcutaneous injection for 12 weeks; Other Names: Placebo Comparator
Placebo Comparator: Placebo , then Elamipretide; Placebo Comparator Part 1: 12 weeks of single daily SC doses of placebo in Treatment Period 1 followed by 12 weeks of treatment with 40 mg elamipretide in Treatment Period 2 (separated by a 4 week washout period). Placebo Comparator Open Label Extension Part 2: All subjects will receive Elamipretide 40mg SC daily injections for up to 168 weeks	Drug: Elamipretide; 40 mg daily subcutaneous injection for 12 weeks; Other Names: MTP-131; Drug: Placebo; daily subcutaneous injection for 12 weeks; Other Names: Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Distance Walked During the 6-Minute Walk Test (6MWT) by Visit	Average distance walked in meters during the 6-minute walk test (6MWT) at end of treatment, where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period.	Pre-dose to Week 12 (end of treatment)
Part 1: Total Fatigue Score Based on the BTHS-SA by Visit.	Total Fatigue Score (Q1, Q2, and Q4) Based on the BarTH Syndrome Symptom Assessment (BTHS-SA) by visit at predose, Weeks 1, 4, 8, and 12 (end of treatment). The BTHS-SA is 3-question fatigue assessment using a 0 to 4-point scale for each question where no fatigue =0 and very severe fatigue =4, with scores from all 3 questions combined and averaged for all subjects; a lower score means better outcome, higher score means a worse outcome. Combined Min score=0, max score =12. Weekly values are based on the weekly average of the last 7 days before the site or visiting nurse visit for both periods. Results from each 12-week period were combined, where end of treatment for Period 1 =Visit 5 (week 12), and End of Period 2 = Visit 10 (week 12)	Pre-dose, Weeks 1, 4, 8, and 12 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Distance Walked During the 6MWT	Change from baseline for distance walked in meters during the 6-minute walk test (6MWT) by visit where Baseline= Part 1 Period 1 Pre-dose	Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192
Part 2: Change From Baseline: Total Fatigue Score (Q1, Q2, and Q4) Based on the BTHS-SA by Visit	Change from Baseline (mean) in Total Fatigue Score (Q1, Q2, and Q4) Based on the BarTH Syndrome Symptom Assessment (BTHS-SA) by visit. The BTHS-SA is 3-question fatigue assessment using a 0-4 point scale for each question where no fatigue =0 and very severe fatigue =4, with scores from all 3 questions combined and averaged for all subjects by visit; a lower score means better outcome, higher score means a worse outcome. Change from baseline: an increase in scores would mean worse outcome, a decrease in scores means better outcome. Combined Min score=-12, max score =12. Weekly values are based on the weekly average of the last 7 days before the site or visiting nurse visit for both periods. Baseline= Period 1 Predose.	Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192
Part 1: Muscle Strength as Measured by HHD by Visit	Muscle strength as measured by handheld dynamometry (HHD) in Newtons, where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period. Handheld dynamometry assesses the average strength of the knee extensors of both legs.	Pre-dose to Week 12 (end of treatment)
Part 2: Change From Baseline: Muscle Strength by HHD (Newtons) by Visit	Muscle strength as measured by handheld dynamometry (HHD) in Newtons. Handheld dynamometry assesses the average strength of the knee extensors of both legs. Change from baseline where Baseline= Part 1 Period 1 Pre-dose: the greater positive change, the better the outcome, the smaller positive change (or negative change) the number the worse the outcome.	Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192
Part 1: 5XSST by Visit	Time (in seconds) to complete the Five Times Sit-To-Stand, where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period.	Pre-dose to Week 12 (end of treatment)
Part 2: Change From Baseline: 5X Sit to Stand by Visit	Change in baseline in time (in seconds), where Baseline= Part 1 Period 1 Pre-dose to complete the Five Times Sit-To-Stand by visit. More time means worse outcome, less time means better outcome.	Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192
Part 1: SWAY Application Balance Assessments by Visit	SWAY application balance assessment consists of five stances each performed for 10 seconds and scores postural stability on a scale from 0-100 with higher scores indicating better postural stability from Pre-dose to Week 12 (end of treatment), where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period.	Pre-dose to Week 12 (end of treatment)
Part 2: Change From Baseline: SWAY Application Balance Assessment	Change from Baseline: SWAY Application Balance Assessment,where Baseline= Part 1 Period 1 Pre-doseSWAY application balance assessment consists of five stances each performed for 10 seconds and scores postural stability on a scale from 0-100 with higher scores indicating better postural stability. An increase from baseline is a better outcome and a decrease in score is a worse outcome.	Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192
Part 1: Patient Global Impression Scales of Symptoms	Patient-reported health status over the past week, by visit, where end of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period. Scores range from 0-40 for adolescents and 0-50 for adults. PGI Scale is as follows: 0=None, 1=Mild, 2=Moderate, 3=Severe, and 4=Very Severe. Higher score means worse health status, means worse outcome; lower score means better health status, means better outcome.	Pre-dose, Week 1, Week 12 (end of treatment)
Part 2: Change From Baseline: Patient Global Impression Scales of Symptoms by Visit	Part 2: Change from Baseline: Patient Global Impression Scales of Symptoms by Visit Patient-reported health status over the past week where Baseline= Part 1 Period 1 Pre-dose, administered at Week 12 for Period 1 and Period 2. Scores range from 0-40 for adolescents and 0-50 for adults. PGI Scale is as follows: 1=None, 2=Mild, 3=Moderate, 4=Severe, and 5=Very Severe. Change from baseline: Higher score means worse health status, means worse outcome; lower score means better health status, means better outcome.	Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192
Part 1: Part 1: Clinician Global Impression	Clinician Global Impression Scale by visit: Clinician-reported overall health status at end of treatment, administered at Week 12 for Period 1 and Period 2. Scores range from 0-6 for both adolescents and adults. PGI Scale is as follows: 1= Very much Better, 2= Moderately Better, 3= A Little Better, 4= No Change, and 5= A Little Worse 6= Very much Worse. Higher score means worse health status, means worse outcome; lower score means better health status, means better outcome. End of treatment means end of Visit 5 (Week 12) for Period 1 and end of Visit 10 (Week 12) for Period 2. Results were pooled for each 12 week period.	Pre-dose to Week 12 (end of treatment)
Part 2: Change From Baseline: CGI Symptom Scale	Change from Baseline: CGI Symptom Scale by visit where Baseline= Part 1 Period 1 Pre-dose. Clinician Global Impression Scale: Clinician-reported overall health status at end of treatment, administered at Week 12 for Period 1 and Period 2. Scores range from 0-6 for both adolescents and adults. PGI Scale is as follows: 1= Very much Better, 2= Moderately Better, 3= A Little Better, 4= No Change, and 5= A Little Worse 6= Very much Worse. Change from baseline: higher score means worse health status, means worse outcome; lower score means better health status, means better outcome.	Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.
• Investigators: Principal Investigator: Hilary Vernon, MD, PhD, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Actual): October 5, 2018
• Study Completion (Actual): October 11, 2021

Study Registration Dates

• First Submitted: March 21, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Barth Syndrome; MTP-131; Stealth; elamipretide; Stealth BT; BTHS
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Lipid Metabolism, Inborn Errors; Syndrome; Barth Syndrome
• Other Study ID Numbers: SPIBA-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No