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

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ClinicalTrials.gov Identifier: NCT02628743
Recruitment Status : Completed
First Posted : December 11, 2015
Results First Posted : August 9, 2019
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE December 1, 2015
First Posted Date  ICMJE December 11, 2015
Results First Submitted Date  ICMJE June 12, 2019
Results First Posted Date  ICMJE August 9, 2019
Last Update Posted Date August 9, 2019
Actual Study Start Date  ICMJE January 20, 2016
Actual Primary Completion Date December 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 3 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
  • Incidence of adverse events [ Time Frame: Up to 4 years ]
  • Safety laboratory tests, Vital signs and electrocardiogram parameters [ Time Frame: Up to 4 years ]
Change History Complete list of historical versions of study NCT02628743 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
  • Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score [ Time Frame: 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.
  • Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Caregiver Proxy EQ-5D-5L VAS Score [ Time Frame: 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.
  • Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2015)
  • Change from baseline in Motor Function Measure (MFM) D1+D2 +D3 score and total score [ Time Frame: Baseline (Week 1), Week 26, Week 52, Week 104, thereafter every 26 weeks up to 4 years ]
  • Change from baseline in Hammersmith Functional Motor Scale (HFMS) score [ Time Frame: Screening (Day -42 to Day -1), Week 13, Week 39, Week 78, Week 130, thereafter every 26 weeks up to 4 years ]
  • Predose (trough) plasma olesoxime concentration at each visit [ Time Frame: Week 1, Week 13, Week 26, Week 52, Week 104, thereafter every 12 months up to 4 years ]
  • The Pediatric Quality of Life Inventory (PedsQL) core scales and neuromuscular sub-scales [ Time Frame: Week 1, Week 26, Week 52, Week 78, Week 104, Week 130, thereafter every 26 weeks up to 4 years ]
  • The EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L) score [ Time Frame: Week 1, Week 26, Week 52, Week 78, Week 104, Week 130, thereafter every 26 weeks up to 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Long Term Safety, Tolerability, and Effectiveness of Olesoxime in Patients With Spinal Muscular Atrophy (SMA)
Official Title  ICMJE Multicenter, Open-Label, Single-Arm Study to Evaluate Long-Term Safety, Tolerability, and Effectiveness of 10 mg/kg BID Olesoxime in Patients With Spinal Muscular Atrophy
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Muscular Atrophy, Spinal
Intervention  ICMJE Drug: Olesoxime
Participants will receive homogeneous suspension of olesoxime.
Study Arms  ICMJE Experimental: Olesoxime

Participants who have consented to the dose increase will receive 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube with breakfast and dinner, preferably at the same time of the day throughout the study. If the drug administration does not coincide with one of the scheduled meals, a snack should be taken prior to drug administration. Preferably there should be at least 10 hours between the morning and evening dose. The total dose in this study will not exceed 2000 mg.

Participants who do not consent to the dose increase will continue with the previous dosage and receive a dose of 10 mg/kg suspension once a day orally or via a naso-gastric or gastronomy tube with the main meal, preferably at the same time of the day.

Intervention: Drug: Olesoxime
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2017)
131
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2015)
171
Actual Study Completion Date  ICMJE December 18, 2018
Actual Primary Completion Date December 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Netherlands,   Poland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02628743
Other Study ID Numbers  ICMJE BN29854
2015-001589-25 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP