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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A 24-Week, Ph1b, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study, to Assess the Safety Profile of Olesoxime in Patients With Stable Relapsing Remitting Multiple Sclerosis Treated With Interferon Beta.

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: olesoxime (TRO19622)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: olesoxime (TRO19622)<br>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). | Drug: olesoxime (TRO19622)<br>* 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).<br>* Other names: TRO19622 (olesoxime);|
| Placebo Comparator: placebo<br>placebo (3 soft capsules, od) will be administered orally for 6 months | Drug: placebo<br>* placebo capsule shells with identical appearance as the active compound TRO19622<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Parameters | Number of Gadolinium-enhancing lesions on T1-weighted images Number of new or enlarged lesions on T2-weighted images | Baseline (Visit 0), Week 12 (Visit 2) and Week 24 (Visit 3/Final Visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, multiple sclerosis, olesoxime, double-blind, randomized