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

Part 1: Distance Walked During the 6-Minute Walk Test (6MWT) by Visit

Time frame · Pre-dose to Week 12 (end of treatment)

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.

Part 1: Total Fatigue Score Based on the BTHS-SA by Visit.

Time frame · Pre-dose, Weeks 1, 4, 8, and 12 (end of treatment)

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)

Part 2: Distance Walked During the 6MWT

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192

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

Part 2: Change From Baseline: Total Fatigue Score (Q1, Q2, and Q4) Based on the BTHS-SA by Visit

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192

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.

Part 1: Muscle Strength as Measured by HHD by Visit

Time frame · Pre-dose to Week 12 (end of treatment)

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.

Part 2: Change From Baseline: Muscle Strength by HHD (Newtons) by Visit

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192

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.

Part 1: 5XSST by Visit

Time frame · Pre-dose to Week 12 (end of treatment)

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.

Part 2: Change From Baseline: 5X Sit to Stand by Visit

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96, 168, 192

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.

Part 1: SWAY Application Balance Assessments by Visit

Time frame · Pre-dose to Week 12 (end of treatment)

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.

Part 2: Change From Baseline: SWAY Application Balance Assessment

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96,168, 192

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.

Part 1: Patient Global Impression Scales of Symptoms

Time frame · Pre-dose, Week 1, Week 12 (end of treatment)

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.

Part 2: Change From Baseline: Patient Global Impression Scales of Symptoms by Visit

Time frame · Baseline to Weeks 12, 24, 36, 48, 72, 96, 120, 144, 168, 192

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.