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

Hoffmann-La Roche24 sites in 7 countries131 target enrollmentJanuary 20, 2016

ConditionsMuscular Atrophy, Spinal

InterventionsOlesoxime

DrugsOlesoxime

Overview

Phase: Phase 2
Intervention: Olesoxime
Conditions: Muscular Atrophy, Spinal
Sponsor: Hoffmann-La Roche
Enrollment: 131
Locations: 24
Primary Endpoint: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

January 20, 2016

End Date

December 18, 2018

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

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: Olesoxime

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

Time Frame: Baseline up to approximately 3 years

Secondary Outcomes

Change From Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
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)
Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
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)
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)
Change From Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
Change From Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
Plasma Concentrations of Olesoxime(Pre-dose (Hour 0) at Weeks 1, 13, 26, 39, 52, 78, 104 and 130)
Change From Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
Change From Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
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)
Change From Baseline in Caregiver Proxy EQ-5D-5L VAS Score(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)
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)
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)
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)
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)
SMA Independence Scale (SMAIS) Score: Patient(Week 104 and Week 130)
SMA Independence Scale (SMAIS) Score: Caregiver(Week 104 and Week 130)
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)
Change From Baseline in SF-36 Domain Scores: Caregiver(Baseline (Week 1), Weeks 26, 52, 78, 104 and 130)