Trial Outcomes & Findings for A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA) (NCT NCT02628743)

NCT ID: NCT02628743

Last Updated: 2019-08-09

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 131 participants
• Primary outcome timeframe: Baseline up to approximately 3 years
• Results posted on: 2019-08-09

Participant Flow

Participant milestones

Measure	Olesoxime Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Overall Study STARTED	131
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	131

Reasons for withdrawal

Measure	Olesoxime Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Overall Study Other	3
Overall Study Withdrawal by Subject	50
Overall Study Study Terminated by Sponsor	76
Overall Study Physician Decision	2

Baseline Characteristics

A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA)

Baseline characteristics by cohort

Measure	Olesoxime n=131 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Age, Continuous	14.7 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	33 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	89 participants n=5 Participants
Race/Ethnicity, Customized Not Stated	29 participants n=5 Participants
Race/Ethnicity, Customized Unknown	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately 3 years

Population: Safety population included all patients who received at least one dose of study medication.

Outcome measures

Measure	Olesoxime n=131 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) SAEs	27.5 percentage of participants
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) AEs	91.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM.

The MFM scale evaluated motor function in three dimensions. D1 evaluates functions related to standing and transfer, D2 evaluates axial and proximal function in supine and sitting position on mat and chair and D3 evaluates distal motor function. The scoring of each task uses a 4-point Likert scale based on the participant's maximal abilities without assistance: 0, cannot initiate the task or maintain the starting position; 1, performs the task partially; 2, performs the task incompletely or imperfectly (with compensatory/uncontrolled movements or slowness); and 3, performs the task fully and "normally". The scores are summed to yield a total score expressed as the percentage of the maximum possible score (the one obtained with no physical impairment); the lower the total score, the more severe the impairment.

Outcome measures

Measure	Olesoxime n=127 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Week 26	-0.06 percentage of maximum score Standard Deviation 4.75
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Week 52	-0.31 percentage of maximum score Standard Deviation 4.61
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Week 78	-1.26 percentage of maximum score Standard Deviation 5.64
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Week 104	-3.32 percentage of maximum score Standard Deviation 7.08
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Week 130	-4.87 percentage of maximum score Standard Deviation 9.91
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score Baseline	30.01 percentage of maximum score Standard Deviation 12.77

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: ITT population includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM

The MFM scale evaluated motor function in three dimensions. D1 evaluates functions related to standing and transfer, D2 evaluates axial and proximal function in supine and sitting position on mat and chair and D3 evaluates distal motor function. The scoring of each task uses a 4-point Likert scale based on the participant's maximal abilities without assistance: 0, cannot initiate the task or maintain the starting position; 1, performs the task partially; 2, performs the task incompletely or imperfectly (with compensatory/uncontrolled movements or slowness); and 3, performs the task fully and "normally". The scores are summed to yield a total score expressed as the percentage of the maximum possible score (the one obtained with no physical impairment); the lower the total score, the more severe the impairment.

Outcome measures

Measure	Olesoxime n=127 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Baseline	41.21 percentage of maximum score Standard Deviation 12.81
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Week 26	0.31 percentage of maximum score Standard Deviation 4.35
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Week 78	-0.64 percentage of maximum score Standard Deviation 5.28
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Week 104	-2.96 percentage of maximum score Standard Deviation 7.09
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Week 52	0.08 percentage of maximum score Standard Deviation 4.08
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score Week 130	-4.02 percentage of maximum score Standard Deviation 9.48

SECONDARY outcome

Timeframe: Pre-dose (Hour 0) at Weeks 1, 13, 26, 39, 52, 78, 104 and 130

Population: Included participants in the safety population that received at least one dose of the study drug and had measurable concentration values.

Values are reported separately for QD and BID doses. Dose increase occurred after Week 104.

Outcome measures

Measure	Olesoxime n=131 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Plasma Concentrations of Olesoxime Week 78	10351.4 ng/mL Standard Deviation 5267.3
Plasma Concentrations of Olesoxime Week 104	8566.4 ng/mL Standard Deviation 5353.1
Plasma Concentrations of Olesoxime Dose Increase Visit (BID)	14797.1 ng/mL Standard Deviation 5773.8
Plasma Concentrations of Olesoxime Week 130 (QD)	6274.6 ng/mL Standard Deviation 6281.9
Plasma Concentrations of Olesoxime Week 130 (BID)	13956.9 ng/mL Standard Deviation 9565.0
Plasma Concentrations of Olesoxime Baseline	129.0 ng/mL Standard Deviation 160.2
Plasma Concentrations of Olesoxime Week 13	9475.5 ng/mL Standard Deviation 3962.5
Plasma Concentrations of Olesoxime Week 26	10021.3 ng/mL Standard Deviation 4885.6
Plasma Concentrations of Olesoxime Week 39	10257.8 ng/mL Standard Deviation 4443.7
Plasma Concentrations of Olesoxime Week 52	9665.6 ng/mL Standard Deviation 4941.8

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM.

The PedsQL Generic Core Scale includes 23 items using self-report and/or parent report (ages 5+). The instrument covers physical, emotional, social and school functioning. Scale items are linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life.

Outcome measures

Measure	Olesoxime n=128 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Baseline (Total Score)	58.69 score on scale Standard Deviation 11.17
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Total Score - Week 26	-0.80 score on scale Standard Deviation 9.10
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Total Score - Week 78	-0.72 score on scale Standard Deviation 10.98
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Total Score - Week 104	-0.35 score on scale Standard Deviation 11.69
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Total Score - Week 130	-0.11 score on scale Standard Deviation 10.83
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Baseline (Physical Score)	28.49 score on scale Standard Deviation 16.50
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Physical Score - Week 26	-1.76 score on scale Standard Deviation 15.99
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Physical Score - Week 52	-4.48 score on scale Standard Deviation 17.68
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Physical Score - Week 78	-3.18 score on scale Standard Deviation 19.67
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Physical Score - Week 104	-1.42 score on scale Standard Deviation 17.87
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Physical Score - Week 130	-3.23 score on scale Standard Deviation 16.33
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Baseline (Emotional Score)	74.61 score on scale Standard Deviation 17.34
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Emotional Score - Week 26	-1.19 score on scale Standard Deviation 18.62
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Emotional Score - Week 52	1.19 score on scale Standard Deviation 16.27
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Emotional Score - Week 104	-0.54 score on scale Standard Deviation 18.37
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Emotional Score - Week 130	2.31 score on scale Standard Deviation 18.47
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Baseline (Social Score)	72.77 score on scale Standard Deviation 18.59
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Social Score - Week 26	1.43 score on scale Standard Deviation 14.15
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Social Score - Week 52	0.93 score on scale Standard Deviation 15.91
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Social Score - Week 78	2.39 score on scale Standard Deviation 17.38
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Social Score - Week 104	2.38 score on scale Standard Deviation 18.62
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Social Score - Week 130	4.10 score on scale Standard Deviation 16.05
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Baseline (School/Work Score)	77.20 score on scale Standard Deviation 15.83
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score School/Work Score - Week 26	-1.24 score on scale Standard Deviation 14.28
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score School/Work Score - Week 52	-1.32 score on scale Standard Deviation 14.09
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score School/Work Score - Week 78	-0.51 score on scale Standard Deviation 14.26
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score School/Work Score - Week 104	-1.65 score on scale Standard Deviation 15.24
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score School/Work Score - Week 130	-2.58 score on scale Standard Deviation 15.04
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Total Score - Week 52	-1.33 score on scale Standard Deviation 10.52
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score Emotional Score - Week 78	-0.05 score on scale Standard Deviation 17.23

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. Scale scores were not computed if more than 50% of items in the scale were missing.

The PedsQL Generic Core Scale includes 23 items. The instrument covers physical, emotional, social and school functioning. Scale items are linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life. Questionnaire was completed by the caregiver.

Outcome measures

Measure	Olesoxime n=121 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Total Score - Week 26	-0.85 score on scale Standard Deviation 13.15
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Total Score - Week 52	-1.86 score on scale Standard Deviation 13.12
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Total Score - Week 78	-0.67 score on scale Standard Deviation 13.88
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Total Score - Week 104	-1.64 score on scale Standard Deviation 17.95
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Total Score - Week 130	-0.33 score on scale Standard Deviation 13.41
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Baseline (Physical Score)	28.99 score on scale Standard Deviation 25.84
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Physical Score - Week 26	-0.58 score on scale Standard Deviation 28.66
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Physical Score - Week 52	-5.10 score on scale Standard Deviation 25.86
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Physical Score - Week 78	-2.91 score on scale Standard Deviation 28.91
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Physical Score - Week 104	-3.28 score on scale Standard Deviation 34.80
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Physical Score - Week 130	-0.56 score on scale Standard Deviation 30.09
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Emotional Score - Week 26	-2.13 score on scale Standard Deviation 15.30
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Emotional Score - Week 52	-0.90 score on scale Standard Deviation 15.08
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Emotional Score - Week 78	-0.39 score on scale Standard Deviation 18.81
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Emotional Score - Week 104	-0.70 score on scale Standard Deviation 20.54
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Emotional Score - Week 130	-0.32 score on scale Standard Deviation 15.94
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Baseline (Social Score)	68.34 score on scale Standard Deviation 16.19
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Social Score - Week 26	-0.42 score on scale Standard Deviation 16.84
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Social Score - Week 52	-0.49 score on scale Standard Deviation 15.92
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Social Score - Week 78	1.47 score on scale Standard Deviation 18.40
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Social Score - Week 104	-0.55 score on scale Standard Deviation 21.72
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Social Score - Week 130	1.25 score on scale Standard Deviation 16.22
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Baseline (School/Work Score)	73.67 score on scale Standard Deviation 17.69
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score School/Work Score - Week 26	-0.31 score on scale Standard Deviation 16.69
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score School/Work Score - Week 52	0.53 score on scale Standard Deviation 18.14
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score School/Work Score - Week 78	0.94 score on scale Standard Deviation 18.39
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Baseline (Total Score)	55.58 score on scale Standard Deviation 12.49
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score Baseline (Emotional Score)	67.48 score on scale Standard Deviation 17.31
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score School/Work Score - Week 104	-0.71 score on scale Standard Deviation 20.64
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score School/Work Score - Week 130	-1.53 score on scale Standard Deviation 16.17

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. Scale scores were not computed if more than 50% of items in the scale were missing.

The PedsQL Neuromuscular Module (Version 3.0) includes 25 items using self-report (ages 5 - 18) and/or parent report (ages 5 -18). The instrument covers problems related to neuromuscular disease, communication and family resources. Scale items are linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life.

Outcome measures

Measure	Olesoxime n=90 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 104	-1.29 score on scale Standard Deviation 19.81
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 130	-0.38 score on scale Standard Deviation 16.36
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Total Score)	69.57 score on scale Standard Deviation 14.01
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 26	-0.98 score on scale Standard Deviation 10.75
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 52	-0.86 score on scale Standard Deviation 12.81
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 78	-1.08 score on scale Standard Deviation 12.11
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 104	-1.18 score on scale Standard Deviation 13.13
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 26	-1.77 score on scale Standard Deviation 12.28
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 52	-2.22 score on scale Standard Deviation 14.29
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 78	-2.69 score on scale Standard Deviation 12.82
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 104	-1.90 score on scale Standard Deviation 15.11
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 130	-3.14 score on scale Standard Deviation 14.20
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Family Resources Score)	74.39 score on scale Standard Deviation 20.10
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 26	-0.11 score on scale Standard Deviation 17.35
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 52	1.44 score on scale Standard Deviation 24.43
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 78	4.85 score on scale Standard Deviation 22.19
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 104	2.98 score on scale Standard Deviation 24.25
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 130	6.57 score on scale Standard Deviation 25.15
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 130	-1.41 score on scale Standard Deviation 12.61
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Neuromuscular)	66.03 score on scale Standard Deviation 15.39
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 52	1.78 score on scale Standard Deviation 16.07
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 78	0.82 score on scale Standard Deviation 19.22
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Communication Score)	81.57 score on scale Standard Deviation 21.14
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 26	2.01 score on scale Standard Deviation 19.86

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. Scale scores were not computed if more than 50% of items in the scale were missing.

The PedsQL Neuromuscular Module (Version 3.0) includes 25 items using self-report (ages 5 - 18) and/or parent report (ages 5 -18). The instrument covers problems related to neuromuscular disease, communication and family resources. Scale items are linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life. Questionnaire was completed by the caregiver.

Outcome measures

Measure	Olesoxime n=88 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Total Score)	59.44 score on scale Standard Deviation 14.83
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 26	0.13 score on scale Standard Deviation 10.12
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 52	-0.11 score on scale Standard Deviation 12.89
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 78	0.65 score on scale Standard Deviation 13.23
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 104	1.21 score on scale Standard Deviation 14.40
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Total Score - Week 130	-0.07 score on scale Standard Deviation 12.86
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Neuromuscular)	56.28 score on scale Standard Deviation 15.70
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 26	-0.64 score on scale Standard Deviation 10.92
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 52	-1.33 score on scale Standard Deviation 13.39
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 104	0.54 score on scale Standard Deviation 15.32
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 130	-1.39 score on scale Standard Deviation 14.65
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Family Resources Score)	58.24 score on scale Standard Deviation 25.08
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 26	1.74 score on scale Standard Deviation 16.57
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 52	2.44 score on scale Standard Deviation 19.04
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 78	0.91 score on scale Standard Deviation 19.31
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Baseline (Communication Score)	79.36 score on scale Standard Deviation 22.92
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 26	1.92 score on scale Standard Deviation 20.08
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 52	2.88 score on scale Standard Deviation 22.31
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 78	3.57 score on scale Standard Deviation 20.92
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 104	4.85 score on scale Standard Deviation 24.24
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Neuromuscular - Week 78	0.05 score on scale Standard Deviation 13.97
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 104	1.27 score on scale Standard Deviation 18.63
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Family Resources Score - Week 130	1.00 score on scale Standard Deviation 17.26
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score Communication Score - Week 130	4.90 score on scale Standard Deviation 22.74

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.

Outcome measures

Measure	Olesoxime n=74 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Week 26	0.0084 score on scale Standard Deviation 0.1563
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Week 52	-0.0164 score on scale Standard Deviation 0.1191
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Week 78	0.0168 score on scale Standard Deviation 0.1910
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Week 104	0.0081 score on scale Standard Deviation 0.1701
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Week 130	-0.0259 score on scale Standard Deviation 0.1232
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score Baseline	0.0471 score on scale Standard Deviation 0.1345

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction. The questionnaire was completed by the caregiver.

Outcome measures

Measure	Olesoxime n=54 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Baseline	0.0429 score on scale Standard Deviation 0.2335
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Week 26	0.0652 score on scale Standard Deviation 0.4091
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Week 78	0.0696 score on scale Standard Deviation 0.3094
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Week 104	0.0699 score on scale Standard Deviation 0.2887
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Week 130	0.0455 score on scale Standard Deviation 0.3323
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score Week 52	0.0203 score on scale Standard Deviation 0.2820

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Outcome measures

Measure	Olesoxime n=75 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Baseline	69.4 score on scale Standard Deviation 19.7
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Week 26	1.3 score on scale Standard Deviation 17.1
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Week 78	1.3 score on scale Standard Deviation 19.9
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Week 104	5.4 score on scale Standard Deviation 17.0
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Week 130	0.6 score on scale Standard Deviation 18.1
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score Week 52	0.2 score on scale Standard Deviation 17.4

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Questionnaire was completed by the caregiver.

Outcome measures

Measure	Olesoxime n=54 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Week 26	-0.3 score on scale Standard Deviation 27.7
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Week 52	0.8 score on scale Standard Deviation 21.2
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Week 78	0.4 score on scale Standard Deviation 20.9
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Week 104	5.7 score on scale Standard Deviation 24.3
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Week 130	0.5 score on scale Standard Deviation 17.9
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score Baseline	72.7 score on scale Standard Deviation 21.4

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities.

Outcome measures

Measure	Olesoxime n=125 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Baseline	56 participants
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Week 52	58 participants
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Week 78	62 participants
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Week 104	56 participants
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Week 130	39 participants
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire Week 26	66 participants

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The WPAI:CG consists of four questions about the effects of SMA on the following: employment status, hours missed due to patient caregiving (HMC), hours missed due to other reasons (HMO), hours actually worked (HAW) and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities.

Outcome measures

Measure	Olesoxime n=56 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire Baseline (HMC)	2.0 hours Standard Deviation 3.7
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMC, Week 26	2.0 hours Standard Deviation 7.3
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMC, Week 52	1.9 hours Standard Deviation 8.2
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMC, Week 78	0.9 hours Standard Deviation 5.6
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMC, Week 104	3.2 hours Standard Deviation 8.3
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMC, Week 130	1.1 hours Standard Deviation 8.1
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire Baseline (HMO)	4.8 hours Standard Deviation 7.3
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMO, Week 26	-1.5 hours Standard Deviation 7.9
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMO, Week 52	-1.5 hours Standard Deviation 9.0
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMO, Week 78	-0.1 hours Standard Deviation 8.6
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMO, Week 104	0.0 hours Standard Deviation 9.6
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HMO, Week 130	0.8 hours Standard Deviation 7.8
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire Baseline (HAW)	36.0 hours Standard Deviation 47.0
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HAW, Week 26	-12.0 hours Standard Deviation 46.7
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HAW, Week 52	-8.3 hours Standard Deviation 49.2
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HAW, Week 78	-8.6 hours Standard Deviation 49.8
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HAW, Week 104	1.2 hours Standard Deviation 14.4
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire HAW, Week 130	1.5 hours Standard Deviation 27.5

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities. WPAI:CG outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. The outcomes are presented for Percent work time missed (WTM), Percent impairment (IMP), Percent overall work impairment (OWI) and Percent activity impairment (AIM).

Outcome measures

Measure	Olesoxime n=121 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score Baseline (WTM)	6.7 percentage Standard Deviation 11.9
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score WTM, Week 104	6.7 percentage Standard Deviation 20.1
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score WTM, Week 130	4.7 percentage Standard Deviation 24.4
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score Baseline (IMP)	29.3 percentage Standard Deviation 26.6
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score IMP, Week 26	-3.0 percentage Standard Deviation 22.8
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score IMP, Week 78	-3.5 percentage Standard Deviation 25.0
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score IMP, Week 104	0.7 percentage Standard Deviation 22.8
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score OWI, Week 104	3.5 percentage Standard Deviation 26.2
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score Baseline (AIM)	45.8 percentage Standard Deviation 29.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score AIM, Week 52	-1.3 percentage Standard Deviation 30.6
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score AIM, Week 78	-6.3 percentage Standard Deviation 32.6
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score AIM, Week 104	-7.6 percentage Standard Deviation 27.8
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score AIM, Week 130	-5.5 percentage Standard Deviation 31.7
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score Baseline (OWI)	33.8 percentage Standard Deviation 28.1
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score OWI, Week 26	-3.6 percentage Standard Deviation 25.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score OWI, Week 52	-3.3 percentage Standard Deviation 25.4
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score WTM, Week 26	7.0 percentage Standard Deviation 22.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score WTM, Week 52	0.8 percentage Standard Deviation 15.4
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score WTM, Week 78	6.2 percentage Standard Deviation 23.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score IMP, Week 52	-1.5 percentage Standard Deviation 27.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score IMP, Week 130	-6.9 percentage Standard Deviation 24.7
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score OWI, Week 78	-3.0 percentage Standard Deviation 31.9
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score OWI, Week 130	-3.4 percentage Standard Deviation 33.3
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score AIM, Week 26	-3.9 percentage Standard Deviation 28.7

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities. WPAI:CG outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

Outcome measures

Measure	Olesoxime n=121 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Baseline (Productivity)	29.3 percentage of impairment Standard Deviation 26.6
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Productivity, Week 26	-3.0 percentage of impairment Standard Deviation 22.8
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Productivity, Week 52	-1.5 percentage of impairment Standard Deviation 27.3
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Productivity, Week 78	-3.5 percentage of impairment Standard Deviation 25.0
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Productivity, Week 104	0.7 percentage of impairment Standard Deviation 22.8
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Productivity, Week 130	-6.9 percentage of impairment Standard Deviation 24.7
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Baseline (Activities)	45.8 percentage of impairment Standard Deviation 29.3
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Activities, Week 26	-3.9 percentage of impairment Standard Deviation 28.7
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Activities, Week 52	-1.3 percentage of impairment Standard Deviation 30.6
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Activities, Week 78	-6.3 percentage of impairment Standard Deviation 32.6
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Activities, Week 104	-7.6 percentage of impairment Standard Deviation 27.8
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire Activities, Week 130	-5.5 percentage of impairment Standard Deviation 31.7

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (physical functioning, role-functioning physical, bodily pain, general health, vitality, social functioning, role-functioning emotional and mental health), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). The 8 domains are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite norm-based t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status. Reported here are the Physical Composite Scores (PCS) and Mental Composite Scores (MCS).

Outcome measures

Measure	Olesoxime n=101 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver Baseline (PCS)	48.07 score on scale Standard Deviation 10.33
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver PCS, Week 26	-0.24 score on scale Standard Deviation 10.95
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver PCS, Week 52	0.27 score on scale Standard Deviation 9.73
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver PCS, Week 78	-0.34 score on scale Standard Deviation 10.87
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver PCS, Week 104	-0.48 score on scale Standard Deviation 10.30
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver PCS, Week 130	1.68 score on scale Standard Deviation 12.94
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver Baseline (MCS)	49.71 score on scale Standard Deviation 10.52
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver MCS, Week 26	-1.05 score on scale Standard Deviation 10.22
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver MCS, Week 52	-1.64 score on scale Standard Deviation 10.06
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver MCS, Week 104	-0.08 score on scale Standard Deviation 7.73
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver MCS, Week 130	-1.21 score on scale Standard Deviation 9.98
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver MCS, Week 78	-0.21 score on scale Standard Deviation 9.30

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (physical functioning, role-functioning physical, bodily pain, general health, vitality, social functioning, role-functioning emotional and mental health), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). The range for all 8 norm-based domains was from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Measure	Olesoxime n=101 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Physical)	44.51 score on scale Standard Deviation 15.97
Change From Baseline in SF-36 Domain Scores: Caregiver Physical, Week 26	1.73 score on scale Standard Deviation 16.36
Change From Baseline in SF-36 Domain Scores: Caregiver Physical, Week 52	2.03 score on scale Standard Deviation 14.23
Change From Baseline in SF-36 Domain Scores: Caregiver Physical, Week 78	1.25 score on scale Standard Deviation 16.16
Change From Baseline in SF-36 Domain Scores: Caregiver Physical, Week 104	2.39 score on scale Standard Deviation 16.61
Change From Baseline in SF-36 Domain Scores: Caregiver Physical, Week 130	6.02 score on scale Standard Deviation 18.87
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Role (Physical))	47.95 score on scale Standard Deviation 8.83
Change From Baseline in SF-36 Domain Scores: Caregiver Role (physical), Week 26	-1.18 score on scale Standard Deviation 10.29
Change From Baseline in SF-36 Domain Scores: Caregiver Role (physical), Week 130	-0.35 score on scale Standard Deviation 10.75
Change From Baseline in SF-36 Domain Scores: Caregiver Bodily pain, Week 130	-2.96 score on scale Standard Deviation 9.82
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (General health)	50.21 score on scale Standard Deviation 10.65
Change From Baseline in SF-36 Domain Scores: Caregiver General health, Week 26	-0.63 score on scale Standard Deviation 10.59
Change From Baseline in SF-36 Domain Scores: Caregiver General health, Week 52	-0.75 score on scale Standard Deviation 9.64
Change From Baseline in SF-36 Domain Scores: Caregiver General health, Week 78	-0.22 score on scale Standard Deviation 10.83
Change From Baseline in SF-36 Domain Scores: Caregiver General health, Week 104	-1.17 score on scale Standard Deviation 11.22
Change From Baseline in SF-36 Domain Scores: Caregiver General health, Week 130	1.07 score on scale Standard Deviation 11.87
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Vitality)	51.28 score on scale Standard Deviation 9.42
Change From Baseline in SF-36 Domain Scores: Caregiver Vitality, Week 26	-1.04 score on scale Standard Deviation 8.48
Change From Baseline in SF-36 Domain Scores: Caregiver Vitality, Week 52	-1.23 score on scale Standard Deviation 7.53
Change From Baseline in SF-36 Domain Scores: Caregiver Vitality, Week 78	-0.03 score on scale Standard Deviation 9.67
Change From Baseline in SF-36 Domain Scores: Caregiver Vitality, Week 104	-0.07 score on scale Standard Deviation 8.16
Change From Baseline in SF-36 Domain Scores: Caregiver Vitality, Week 130	0.37 score on scale Standard Deviation 8.57
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Social)	48.01 score on scale Standard Deviation 9.49
Change From Baseline in SF-36 Domain Scores: Caregiver Social, Week 26	-0.67 score on scale Standard Deviation 10.60
Change From Baseline in SF-36 Domain Scores: Caregiver Social, Week 52	-1.24 score on scale Standard Deviation 11.14
Change From Baseline in SF-36 Domain Scores: Caregiver Social, Week 78	0.28 score on scale Standard Deviation 10.29
Change From Baseline in SF-36 Domain Scores: Caregiver Social, Week 104	-0.95 score on scale Standard Deviation 9.12
Change From Baseline in SF-36 Domain Scores: Caregiver Social, Week 130	0.35 score on scale Standard Deviation 10.46
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Role (emotional))	48.38 score on scale Standard Deviation 9.58
Change From Baseline in SF-36 Domain Scores: Caregiver Role (emotional), Week 52	-1.72 score on scale Standard Deviation 11.38
Change From Baseline in SF-36 Domain Scores: Caregiver Role (emotional), Week 130	-0.43 score on scale Standard Deviation 9.87
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Mental health)	48.46 score on scale Standard Deviation 9.39
Change From Baseline in SF-36 Domain Scores: Caregiver Mental health, Week 26	-0.24 score on scale Standard Deviation 9.73
Change From Baseline in SF-36 Domain Scores: Caregiver Mental health, Week 52	-0.50 score on scale Standard Deviation 9.15
Change From Baseline in SF-36 Domain Scores: Caregiver Mental health, Week 78	0.07 score on scale Standard Deviation 7.77
Change From Baseline in SF-36 Domain Scores: Caregiver Mental health, Week 104	1.32 score on scale Standard Deviation 7.42
Change From Baseline in SF-36 Domain Scores: Caregiver Mental health, Week 130	-0.29 score on scale Standard Deviation 9.21
Change From Baseline in SF-36 Domain Scores: Caregiver Role (physical), Week 52	-0.76 score on scale Standard Deviation 9.45
Change From Baseline in SF-36 Domain Scores: Caregiver Role (physical), Week 78	-1.02 score on scale Standard Deviation 9.82
Change From Baseline in SF-36 Domain Scores: Caregiver Role (physical), Week 104	-1.05 score on scale Standard Deviation 8.92
Change From Baseline in SF-36 Domain Scores: Caregiver Baseline (Bodily pain)	50.94 score on scale Standard Deviation 8.77
Change From Baseline in SF-36 Domain Scores: Caregiver Bodily pain, Week 26	-1.82 score on scale Standard Deviation 8.75
Change From Baseline in SF-36 Domain Scores: Caregiver Bodily pain, Week 52	-1.83 score on scale Standard Deviation 9.04
Change From Baseline in SF-36 Domain Scores: Caregiver Bodily pain, Week 78	-2.14 score on scale Standard Deviation 10.55
Change From Baseline in SF-36 Domain Scores: Caregiver Bodily pain, Week 104	-2.40 score on scale Standard Deviation 8.44
Change From Baseline in SF-36 Domain Scores: Caregiver Role (emotional), Week 26	-1.15 score on scale Standard Deviation 10.59
Change From Baseline in SF-36 Domain Scores: Caregiver Role (emotional), Week 78	-1.16 score on scale Standard Deviation 10.58
Change From Baseline in SF-36 Domain Scores: Caregiver Role (emotional), Week 104	-1.06 score on scale Standard Deviation 8.03

SECONDARY outcome

Timeframe: Baseline (Week 1), Weeks 26, 52, 78, 104 and 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The SF-6D focuses on seven of the eight health domains covered by the SF-36: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. SF-6D Health Utility Index (HUI) Score = 0 (worst measured health state) to 1 (best measured health state).

Outcome measures

Measure	Olesoxime n=98 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Baseline	0.70 score on scale Standard Deviation 0.11
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Week 26	-0.01 score on scale Standard Deviation 0.12
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Week 52	-0.01 score on scale Standard Deviation 0.10
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Week 78	-0.01 score on scale Standard Deviation 0.12
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Week 104	0.00 score on scale Standard Deviation 0.11
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver Week 130	0.01 score on scale Standard Deviation 0.13

SECONDARY outcome

Timeframe: Week 104 and Week 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The SMAIS was developed specifically for SMA in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities, such as eating or transferring to/from a wheelchair. Each item is scored on a zero to four scale (with an additional option to indicate that an item is non-applicable). Item scores are summed to create the total score. The range of total score is between 0 and 116. Lower scores indicate greater dependence on another individual.

Outcome measures

Measure	Olesoxime n=14 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
SMA Independence Scale (SMAIS) Score: Patient Week 104	71.7 score on scale Standard Deviation 23.4
SMA Independence Scale (SMAIS) Score: Patient Week 130	74.8 score on scale Standard Deviation 22.5

SECONDARY outcome

Timeframe: Week 104 and Week 130

Population: Intent-to-Treat Population (ITT) includes all participants who received at least one dose of study medication and have at least one post-baseline assessment of MFM. The number analyzed represents participants who completed the questionnaire.

The SMAIS was developed specifically for SMA in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities, such as eating or transferring to/from a wheelchair. Each item is scored on a zero to four scale (with an additional option to indicate that an item is non-applicable). Item scores are summed to create the total score. The range of total score is between 0 and 116. Lower scores indicate greater dependence on another individual.

Outcome measures

Measure	Olesoxime n=21 Participants Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
SMA Independence Scale (SMAIS) Score: Caregiver Week 104	60.1 score on scale Standard Deviation 22.2
SMA Independence Scale (SMAIS) Score: Caregiver Week 130	58.0 score on scale Standard Deviation 24.9

Adverse Events

Olesoxime

Serious events: 36 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olesoxime n=131 participants at risk Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Gastrointestinal disorders CONSTIPATION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders VOMITING	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations BRONCHITIS	2.3% 3/131 • Number of events 5 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations GASTROENTERITIS	1.5% 2/131 • Number of events 2 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	1.5% 2/131 • Number of events 3 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders LUNG DISORDER	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders GASTRITIS	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations ENCEPHALITIS	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations GASTROINTESTINAL INFECTION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations LOWER RESPIRATORY TRACT INFECTION	3.1% 4/131 • Number of events 7 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations LUNG INFECTION	1.5% 2/131 • Number of events 2 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations OSTEOMYELITIS	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations PNEUMONIA	7.6% 10/131 • Number of events 13 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations PNEUMONIA VIRAL	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations POSTOPERATIVE WOUND INFECTION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations RESPIRATORY TRACT INFECTION	0.76% 1/131 • Number of events 3 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations URINARY TRACT INFECTION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders PATHOLOGICAL FRACTURE	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders OBSTRUCTIVE AIRWAYS DISORDER	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISTRESS	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	1.5% 2/131 • Number of events 4 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Reproductive system and breast disorders TESTICULAR TORSION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Surgical and medical procedures MEDICAL DEVICE REMOVAL	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Surgical and medical procedures SKIN GRAFT	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications ACCIDENTAL OVERDOSE	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications FALL	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications FEMORAL NECK FRACTURE	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications FEMUR FRACTURE	1.5% 2/131 • Number of events 2 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications HUMERUS FRACTURE	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications JOINT DISLOCATION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications POSTOPERATIVE WOUND COMPLICATION	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications PROCEDURAL HAEMORRHAGE	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications PROCEDURAL PAIN	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications PROCEDURAL PNEUMOTHORAX	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Injury, poisoning and procedural complications THERMAL BURN	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Metabolism and nutrition disorders FOOD REFUSAL	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Psychiatric disorders ANXIETY	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Psychiatric disorders DEPRESSED MOOD	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Renal and urinary disorders NEPHROLITHIASIS	0.76% 1/131 • Number of events 1 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.

Other adverse events

Measure	Olesoxime n=131 participants at risk Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	6.1% 8/131 • Number of events 12 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders CONSTIPATION	6.9% 9/131 • Number of events 13 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders DIARRHOEA	15.3% 20/131 • Number of events 34 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders NAUSEA	6.9% 9/131 • Number of events 13 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Gastrointestinal disorders VOMITING	17.6% 23/131 • Number of events 43 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
General disorders PYREXIA	21.4% 28/131 • Number of events 40 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations BRONCHITIS	11.5% 15/131 • Number of events 22 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations GASTROENTERITIS	9.9% 13/131 • Number of events 18 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations INFLUENZA	9.9% 13/131 • Number of events 14 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations NASOPHARYNGITIS	22.9% 30/131 • Number of events 57 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations PHARYNGITIS	5.3% 7/131 • Number of events 9 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations RHINITIS	7.6% 10/131 • Number of events 15 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	27.5% 36/131 • Number of events 63 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders ARTHRALGIA	9.2% 12/131 • Number of events 14 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders BACK PAIN	6.9% 9/131 • Number of events 16 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	6.1% 8/131 • Number of events 8 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Nervous system disorders HEADACHE	17.6% 23/131 • Number of events 44 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders COUGH	13.0% 17/131 • Number of events 23 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	12.2% 16/131 • Number of events 29 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.
Skin and subcutaneous tissue disorders RASH	6.1% 8/131 • Number of events 10 • Baseline up to approximately 3 years Safety population included all patients who received at least one dose of study medication.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER