Safety Study of Olesoxime in Patients With Stable Relapsing Remitting Multiple Sclerosis Treated With Interferon Beta.

Phase 1

Completed

• Conditions: Relapsing Remitting Multiple Sclerosis
• Interventions: Drug: olesoxime (TRO19622); Drug: placebo

• Registration Number: NCT01808885
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This is a 24-week phase 1b, randomized, double-blind, placebo-controlled, parallel-group, multicenter safety study comparing the tolerance profile of olesoxime (495 mg, od) when administered on top of Interferon beta in patients with stable Relapsing Remitting Multiple Sclerosis. Patients will be randomly allocated to olesoxime (495 mg, od) or placebo in a 1:1 ratio.

Detailed Description

The primary objective of this study is to characterize the general safety and tolerability of olesoxime (495 mg, od), compared to placebo when administered in combination with Interferon beta over a 24-week treatment period in patients with stable Relapsing Remitting Multiple Sclerosis.

The secondary objective of this study is to evaluate the feasibility of multicenter protocols for measurement of neurodegeneration and remyelination by MRI as well as the plasma exposure to olesoxime (495 mg, od).

MRI will be performed to all patients to assess effects of olesoxime on brain inflammation as well as to assess measures of brain atrophy, neuronal damage and myelination status at Baseline, 12 weeks and 24 weeks.

Study Timeline

• Study First Submitted: 2013-02-12
• Study First Submitted QC: 2013-03-08
• Study First Posted: 2013-03-11
• Study Start: 2013-04
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-21
• Last Update Posted: 2016-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Men and women ≥ 18 years old
• Diagnosed with Relapsing Remitting Multiple Sclerosis. Patients must be stable defined as free from relapsing episode for at least 6 months prior to Baseline
• Patients must be treated with Interferon beta for at least one year
• Patients must have an Expanded Disability Status Scale (EDSS) score ≤ 5
• Female patients must be post-menopausal (defined as at least 12 months post cessation of menses), surgically sterile or, if of childbearing potential, using a reliable method of contraception for at least 3 months prior to Baseline and during the study. In addition, female patients must not be lactating
• Patients must be able to understand and comply with study requirements
• Patients must provide a written, dated and signed informed consent prior to any study procedure

Exclusion Criteria

• Any relapse of multiple sclerosis within the past 6 months prior to Screening Visit/Visit -1
• Any change in Interferon treatment within the past year prior to Screening Visit (Visit -1)
• Expected use of another disease modifying therapy from Screening Visit/Visit -1 to Visit 3/Final Visit
• Patients unable to undergo MRI scan
• Current or expected use of a medication that could interfere with olesoxime pharmacology (e.g. tamoxifen)
• Current or expected use of lipid lowering agents (ezetimibe, bile salt chelators, fibrates, phytosterols) other than statins
• Known hypersensitivity to olesoxime or any of its components
• History of alcohol or drug abuse within the last 6 months, or addiction within the last 2 years prior to Baseline Visit
• Positive urinary pregnancy test at Baseline Visit
• History of hepatitis B/C or HIV positive serology
• Hepatic impairment (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)> 3 × ULN) at Baseline Visit
• History of renal impairment defined by a serum creatinine value > 176 μmol/L (2.0 mg/dL) at Baseline Visit
• Abnormal and clinically significant ECG at Screening Visit/Visit -1 as assessed by a cardiologist
• Current or expected use of oral or intramuscular corticosteroids within 3 months prior to the Screening Visit. Only stable dose regimens of inhaled and topical corticosteroids are allowed during the study
• History of any clinically relevant gastrointestinal (GI), respiratory, psychiatric, neurological, kidney, liver, cardiac diseases, bleeding disorder, other disease/condition or abnormal physical finding which may interfere with the study objectives or put the patient's safety at risk, as judged by the Investigator
• Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than Multiple Sclerosis (MS)
• History of malignancy of any organ, treated or non-treated within the past 5 years
• Current participation or participation within 30 days prior to study entry, in another investigational drug or device study, or previous enrolment in the present study
• Any direct involvement with the study conduct at site or any family link with study site staff
• Pregnant, parturient or lactating women, as per Public Health Code (CSP)(Article L-1121-5)
• Persons deprived of their liberty by a judicial or administrative decision, and those admitted to a health or social facility, as per CSP (Article L-1121-6)
• Persons covered by a measure of legal protection or unable to provide a written, dated and signed informed consent, as per CSP(Article L-1121-8)
• Patient without Social Security Insurance

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
olesoxime (TRO19622)	olesoxime (TRO19622)	olesoxime (3 caps: 495 mg, od) will be administered orally as 165 mg soft capsules for 6 months. Investigational products will be allocated in a 1:1 ratio from Baseline/Visit 0 to Week 24 (Visit 3/Final Visit).
placebo	placebo	placebo (3 soft capsules, od) will be administered orally for 6 months

Primary Outcome Measures

Name	Time	Method
Safety criteria	The primary endpoint of this study will be the cumulative incidence of AE/SAE assessed by ongoing monitoring at week 24 (day 168)	Cumulative incidence of adverse events/serious adverse events (i.e. total number per patient) as assessed by ongoing monitoring.

Secondary Outcome Measures

Name	Time	Method
MRI Parameters	Baseline (Visit 0), Week 12 (Visit 2) and Week 24 (Visit 3/Final Visit)	1. Number of Gadolinium-enhancing lesions on T1-weighted images; 2. Number of new or enlarged lesions on T2-weighted images

Trial Locations

Locations (3)

Timone University Hospital, Neurology Department, UMR CRMBM CNRS 6612; 🇫🇷 Marseille, France

CHU Pontchaillou, Neurology Department; 🇫🇷 Rennes, France

CHU Reims, Maison Blanche Hospital, Neurology Department & University of Reims; 🇫🇷 Reims, France