Muscular Atrophy, Spinal
Conditions
Brief summary
The purpose of this open-label, single arm study is to further evaluate long-term tolerability, safety and efficacy outcomes of olesoxime in participants with Spinal Muscular Atrophy (SMA) who previously participated in one of the following two clinical studies: TRO19622 CL E Q 1115-1 (open-label Phase Ib, multicenter, single- and multiple- dose study) or TRO19622 CL E Q 1275-1 (NCT01302600, Phase II/III, adaptive, parallel-group, double blind, randomized, placebo-controlled, multicenter, multinational study).
Interventions
DRUGOlesoxime
Participants will receive homogeneous suspension of olesoxime.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Participation in the previous studies (TRO19622 CL E Q 1115-1 or TRO19622 CL E Q 1275-1) * For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 28 days after the last dose of olesoxime
Exclusion criteria
* Female participants who are pregnant or lactating, or intending to become pregnant during the study * Participants who, in the opinion of the investigator, are not suitable to participate in this open-label study * Participants who have developed study drug hypersensitivity to olesoxime or one of the formulation excipients, including sesame oil * Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening * Concomitant or previous participation in a survival motor neuron 2 (SMN2) targeting antisense oligonucleotide study within 6 months prior to screening * History of human immunodeficiency virus infection, history of Hepatitis B infection within the past year, history of Hepatitis C infection which has not been adequately treated * History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment * Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study * History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Baseline up to approximately 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Plasma Concentrations of Olesoxime | Pre-dose (Hour 0) at Weeks 1, 13, 26, 39, 52, 78, 104 and 130 | Values are reported separately for QD and BID doses. Dose increase occurred after Week 104. |
| Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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). |
| Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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). |
| Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
| Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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). |
| SMA Independence Scale (SMAIS) Score: Patient | Week 104 and Week 130 | 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. |
| SMA Independence Scale (SMAIS) Score: Caregiver | Week 104 and Week 130 | 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. |
| Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Baseline (Week 1), Weeks 26, 52, 78, 104 and 130 | 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. |
Countries
Belgium, France, Germany, Italy, Netherlands, Poland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 131 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 3 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Study Terminated by Sponsor | 76 |
| Overall Study | Withdrawal by Subject | 50 |
Baseline characteristics
| Characteristic | Olesoxime |
|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 5.9 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 89 participants |
| Race/Ethnicity, Customized Not Stated | 29 participants |
| Race/Ethnicity, Customized Unknown | 12 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 33 Participants |
| Race (NIH/OMB) White | 94 Participants |
| Sex: Female, Male Female | 66 Participants |
| Sex: Female, Male Male | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 131 |
| other Total, other adverse events | 105 / 131 |
| serious Total, serious adverse events | 36 / 131 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Time frame: Baseline up to approximately 3 years
Population: Safety population included all patients who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olesoxime | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | SAEs | 27.5 percentage of participants |
| Olesoxime | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | AEs | 91.6 percentage of participants |
Secondary
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score | Physical Score - Week 104 | -3.28 score on scale | Standard Deviation 34.8 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score | Emotional Score - Week 26 | -2.13 score on scale | Standard Deviation 15.3 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score | Social Score - Week 78 | 1.47 score on scale | Standard Deviation 18.4 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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
Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score | Total Score - Week 104 | 1.21 score on scale | Standard Deviation 14.4 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Neuromuscular) | 56.28 score on scale | Standard Deviation 15.7 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score | Baseline | 0.0429 score on scale | Standard Deviation 0.2335 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score | Week 52 | 0.0203 score on scale | Standard Deviation 0.282 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Baseline | 72.7 score on scale | Standard Deviation 21.4 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Week 26 | -0.3 score on scale | Standard Deviation 27.7 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Week 52 | 0.8 score on scale | Standard Deviation 21.2 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Week 78 | 0.4 score on scale | Standard Deviation 20.9 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Week 104 | 5.7 score on scale | Standard Deviation 24.3 |
| Olesoxime | Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score | Week 130 | 0.5 score on scale | Standard Deviation 17.9 |
Secondary
Change From Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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
Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 0.191 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire | Baseline (HAW) | 36.0 hours | Standard Deviation 47 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score | Baseline | 41.21 percentage of maximum score | Standard Deviation 12.81 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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
Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 9.1 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 16.5 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Total Score) | 69.57 score on scale | Standard Deviation 14.01 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Neuromuscular) | 66.03 score on scale | Standard Deviation 15.39 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Neuromuscular - Week 26 | -1.77 score on scale | Standard Deviation 12.28 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Neuromuscular - Week 52 | -2.22 score on scale | Standard Deviation 14.29 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Neuromuscular - Week 78 | -2.69 score on scale | Standard Deviation 12.82 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Neuromuscular - Week 104 | -1.90 score on scale | Standard Deviation 15.11 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Neuromuscular - Week 130 | -3.14 score on scale | Standard Deviation 14.2 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Family Resources Score) | 74.39 score on scale | Standard Deviation 20.1 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score | Baseline (Communication Score) | 81.57 score on scale | Standard Deviation 21.14 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Baseline | 0.70 score on scale | Standard Deviation 0.11 |
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Week 26 | -0.01 score on scale | Standard Deviation 0.12 |
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Week 52 | -0.01 score on scale | Standard Deviation 0.1 |
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Week 78 | -0.01 score on scale | Standard Deviation 0.12 |
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Week 104 | 0.00 score on scale | Standard Deviation 0.11 |
| Olesoxime | Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver | Week 130 | 0.01 score on scale | Standard Deviation 0.13 |
Secondary
Change From Baseline in SF-36 Domain Scores: Caregiver
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Physical) | 44.51 score on scale | Standard Deviation 15.97 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Physical, Week 26 | 1.73 score on scale | Standard Deviation 16.36 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Physical, Week 52 | 2.03 score on scale | Standard Deviation 14.23 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Physical, Week 78 | 1.25 score on scale | Standard Deviation 16.16 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Physical, Week 104 | 2.39 score on scale | Standard Deviation 16.61 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Physical, Week 130 | 6.02 score on scale | Standard Deviation 18.87 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Role (Physical)) | 47.95 score on scale | Standard Deviation 8.83 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (physical), Week 26 | -1.18 score on scale | Standard Deviation 10.29 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (physical), Week 52 | -0.76 score on scale | Standard Deviation 9.45 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (physical), Week 78 | -1.02 score on scale | Standard Deviation 9.82 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (physical), Week 104 | -1.05 score on scale | Standard Deviation 8.92 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (physical), Week 130 | -0.35 score on scale | Standard Deviation 10.75 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Bodily pain) | 50.94 score on scale | Standard Deviation 8.77 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Bodily pain, Week 26 | -1.82 score on scale | Standard Deviation 8.75 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Bodily pain, Week 52 | -1.83 score on scale | Standard Deviation 9.04 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Bodily pain, Week 78 | -2.14 score on scale | Standard Deviation 10.55 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Bodily pain, Week 104 | -2.40 score on scale | Standard Deviation 8.44 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Bodily pain, Week 130 | -2.96 score on scale | Standard Deviation 9.82 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (General health) | 50.21 score on scale | Standard Deviation 10.65 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | General health, Week 26 | -0.63 score on scale | Standard Deviation 10.59 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | General health, Week 52 | -0.75 score on scale | Standard Deviation 9.64 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | General health, Week 78 | -0.22 score on scale | Standard Deviation 10.83 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | General health, Week 104 | -1.17 score on scale | Standard Deviation 11.22 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | General health, Week 130 | 1.07 score on scale | Standard Deviation 11.87 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Vitality) | 51.28 score on scale | Standard Deviation 9.42 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Vitality, Week 26 | -1.04 score on scale | Standard Deviation 8.48 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Vitality, Week 52 | -1.23 score on scale | Standard Deviation 7.53 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Vitality, Week 78 | -0.03 score on scale | Standard Deviation 9.67 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Vitality, Week 104 | -0.07 score on scale | Standard Deviation 8.16 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Vitality, Week 130 | 0.37 score on scale | Standard Deviation 8.57 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Social) | 48.01 score on scale | Standard Deviation 9.49 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Social, Week 26 | -0.67 score on scale | Standard Deviation 10.6 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Social, Week 52 | -1.24 score on scale | Standard Deviation 11.14 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Social, Week 78 | 0.28 score on scale | Standard Deviation 10.29 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Social, Week 104 | -0.95 score on scale | Standard Deviation 9.12 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Social, Week 130 | 0.35 score on scale | Standard Deviation 10.46 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Role (emotional)) | 48.38 score on scale | Standard Deviation 9.58 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (emotional), Week 26 | -1.15 score on scale | Standard Deviation 10.59 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (emotional), Week 52 | -1.72 score on scale | Standard Deviation 11.38 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (emotional), Week 78 | -1.16 score on scale | Standard Deviation 10.58 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (emotional), Week 104 | -1.06 score on scale | Standard Deviation 8.03 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Role (emotional), Week 130 | -0.43 score on scale | Standard Deviation 9.87 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Baseline (Mental health) | 48.46 score on scale | Standard Deviation 9.39 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Mental health, Week 26 | -0.24 score on scale | Standard Deviation 9.73 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Mental health, Week 52 | -0.50 score on scale | Standard Deviation 9.15 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Mental health, Week 78 | 0.07 score on scale | Standard Deviation 7.77 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Mental health, Week 104 | 1.32 score on scale | Standard Deviation 7.42 |
| Olesoxime | Change From Baseline in SF-36 Domain Scores: Caregiver | Mental health, Week 130 | -0.29 score on scale | Standard Deviation 9.21 |
Secondary
Change From Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 10.3 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 9.3 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Change From Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
| Olesoxime | 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 |
Secondary
Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) 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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Baseline | 56 participants |
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Week 26 | 66 participants |
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Week 52 | 58 participants |
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Week 78 | 62 participants |
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Week 104 | 56 participants |
| Olesoxime | Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire | Week 130 | 39 participants |
Secondary
Plasma Concentrations of Olesoxime
Values are reported separately for QD and BID doses. Dose increase occurred after Week 104.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | Plasma Concentrations of Olesoxime | Week 130 (QD) | 6274.6 ng/mL | Standard Deviation 6281.9 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 130 (BID) | 13956.9 ng/mL | Standard Deviation 9565 |
| Olesoxime | Plasma Concentrations of Olesoxime | Baseline | 129.0 ng/mL | Standard Deviation 160.2 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 13 | 9475.5 ng/mL | Standard Deviation 3962.5 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 26 | 10021.3 ng/mL | Standard Deviation 4885.6 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 39 | 10257.8 ng/mL | Standard Deviation 4443.7 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 52 | 9665.6 ng/mL | Standard Deviation 4941.8 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 78 | 10351.4 ng/mL | Standard Deviation 5267.3 |
| Olesoxime | Plasma Concentrations of Olesoxime | Week 104 | 8566.4 ng/mL | Standard Deviation 5353.1 |
| Olesoxime | Plasma Concentrations of Olesoxime | Dose Increase Visit (BID) | 14797.1 ng/mL | Standard Deviation 5773.8 |
Secondary
SMA Independence Scale (SMAIS) Score: Caregiver
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | SMA Independence Scale (SMAIS) Score: Caregiver | Week 104 | 60.1 score on scale | Standard Deviation 22.2 |
| Olesoxime | SMA Independence Scale (SMAIS) Score: Caregiver | Week 130 | 58.0 score on scale | Standard Deviation 24.9 |
Secondary
SMA Independence Scale (SMAIS) Score: Patient
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olesoxime | SMA Independence Scale (SMAIS) Score: Patient | Week 104 | 71.7 score on scale | Standard Deviation 23.4 |
| Olesoxime | SMA Independence Scale (SMAIS) Score: Patient | Week 130 | 74.8 score on scale | Standard Deviation 22.5 |