Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study

Wrist Accelerometer Counts by the last 7 days prior to the date of the end of treatment visit; End of treatment being end of Week 4 for Treatment Period 1 and end of Week 12 for Treatment Period 2. Subjects wore an activity monitor, or wrist accelerometer, on their wrist daily (from the Screening Visit to the End-of-Study/Early Discontinuation Visit). As a measure of physical activity and mobility, subjects wore an activity monitor, or wrist accelerometer, which measured mean vector magnitude of accelerations per daywith higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data were used for the analysis of as the vector magnitude of the wrist data.

Average Hip Accelerator Counts by last 7 days predose, and prior to end of treatment; End of treatment being Week 4 for Treatment Period 1 and Week 12 for Treatment Period 2. As a measure of physical activity and mobility, subjects wore an activity monitor, or hip accelerometer, on their hip (or belt line) daily during waking hours (minimum of at least 7 consecutive days immediately prior to study drug administration in each Treatment Period \[Predose; at Visit 2 for Treatment Period 1 and at Visit 4 for Treatment Period 2\]), and at the end of each Treatment Period \[at Visit 3 for Treatment Period 1 and Visit 5 for Treatment Period 2\]), which measured average acceleration per day, with higher counts indicating a more active status. Raw acceleration data was converted into proprietary counts which was used to estimate physical activity. The data was transformed from 30 Hz data into 1 minute epoch data; this 1 minute epoch data was used for the analysis of mean vertical axis (Y) cou

Participants respond to the following statements of the Quality of Life in Neurological Disorders Fatigue Assessment (Neuro-QOL Fatigue Item Bank at end of treatment: 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; I had to limit my social activity because I was tired.Individual response options range from a score of 1 to 5, where 1=Never, 2=Rarely, 3=Sometimes, 4=Often, and 5=Always for end of treatment, where end of treatment period is end of week 4 for period 1, and end of week 12 for period 2. Raw scores are calculated as simple summed scores to an Item Response Theory Metric referred to as the T-score metric. Higher T-score means more fatigue, which means a worse outcome, with possible scores ranging from 29.5 to 74.1. Mean population T-score and standard deviation was reported.

Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue score at end of treatment (sum of Q1 to Q4; tiredness/muscle weakness) 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. Participants rate the following: Tiredness at rest, Tiredness during activities, Muscle weakness at rest, Muscle weakness during activities, at the end of each treatment period, where end of treatment period is the weekly average of the last 7 days of week 4 for period 1 and the last 7 days of week 12 for period 2.

Participant performed 3TUG test after the 6MWT, and after at least 15 minutes rest prior to study drug administration in each Treatment Period (End of Week 4 for Period 1 and End of Week 12 for Period 2.) Participant was directed to stand up from chair, walk at normal pace to the line on the floor 3 meters away,turn, walk back to the chair at normal pace, sit down again; activity was timed, in seconds. Activity is repeated 3 times consecutively without rest and an average time is calculated.

Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome.

Patient-reported current health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2. PGA Scale is as follows: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher score means worse health status, means worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.

Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome.

Physician Global Assessment (PhGA) Physician-reported overall health status at end of treatment, where end of treatment means End of Week 4 for Period 1 and End of Week 12 for Period 2.: 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor. Higher scores equal worse outcome. Excellent means excellent health, means better outcome; poor means poor health, means worse outcome.