A Long-term Extension of Study GNC-401

Study Overview
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Brief Summary
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This Phase II study is a monocenter, long-term extension study of study GNC-401 and will start after individual completion of Week 48 of the GNC-401 study. At entry, all patients will receive active treatment with temelimab. The patients of the placebo group in study GNC-401 will be re-randomized to temelimab 18 mg/kg, 36 mg/kg or 54 mg/kg (1:1:1), while the patients who received temelimab in study GNC-401 will continue with the same dose in study GNC-402. Following final analysis of the results of the GNC-401 study, the Sponsor may switch all patients to an optimal dose of temelimab based on safety and efficacy demonstrated in the GNC-401 study.

Official Title
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A Long-term Extension of Study GNC-401 With Temelimab in Patients With Relapsing Forms of Multiple Sclerosis (RMS) Under Treatment With Rituximab

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Temelimab 18 mg/kg
* Drug: Temelimab 36mg/kg
* Drug: Temelimab 54 mg/kg


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: The patient has given written informed consent to participate in the study; Current diagnosis of RMS, based on the McDonald 2017 criteria ; Patients must have completed study GNC-401. Completion is defined as having performed the Week 48 assessments of study GNC 401; Have no clinical (relapses) or MRI signs (≥2 new T2 lesions of >10 mm diameter) of acute MS disease activity, based on the Week 48 MRI of study GNC 401, or, if yes, been retreated prior to study entry with rituximab; Have a B cell count ≤0.05 x 109 CD19 cells/L (assessed at the end of study GNC 401, or before inclusion in this study GNC 402 (available result from routine clinical practice); if not retreated with rituximab before entering study GNC-402, monthly B-cell count will be executed and retreatment will be considered by the treating physician when B-cells are >0.05 x 109 CD19 cells/L); Main exclusion criteria The emergence of any disease diagnosis during the course of study GNC-401 that is not due to MS and could better explain the patient's neurological signs and symptoms; Body weight ≤40 kg; Contraindication to continue rituximab therapy; Has received rituximab less than 12 days prior to study entry; Use of any of the following medications since Week 48 of the GNC 401 study: Interferon (IFN) β, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide; Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation; Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine; Any experimental drugs for the treatment of MS; Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater lymphopenia (based on Week 48 of study GNC 401); Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including: Diagnosis or history of schizophrenia; Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation; Current or past (within the last 2 years) alcohol or drug abuse; History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association [NYHA] class 3 or 4); Known inability to undergo an MRI scan; Contraindications to the use of 5% glucose solution for infusion; Inability to follow study instructions, or complete study assessments, as defined by the protocol; Any history of cancer with the exceptions of basal cell carcinoma and/or carcinoma in situ of the cervix, and only if successfully treated by complete surgical resection, with documented clean margins and any medically unstable condition as determined by the Investigator; Pregnant or breastfeeding women; Abnormal liver function tests: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 times upper limit of normal range (ULN), or conjugated bilirubin >2 times ULN, or alkaline phosphatase (AP) or gamma-glutamyl transferase (GGT) >3 times ULN;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Temelimab 18 mg/kg<br>Monthly IV repeated dose | Drug: Temelimab 18 mg/kg<br>* temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)<br>|
| Experimental: Temelimab 36 mg/kg<br>Monthly IV repeated dose | Drug: Temelimab 36mg/kg<br>* temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)<br>|
| Experimental: Temelimab 54 mg/kg<br>Monthly IV repeated dose | Drug: Temelimab 54 mg/kg<br>* temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability:adverse event | Number of Patients With Treatment-Related Adverse Events | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuroimaging | Change in Brain parenchymal volume fraction at Week 48 compared to Baseline | 48 weeks | 
| Neuroimaging | change in magnetization transfer Saturation (MTSat) in periventricular NAWM at at Week 48 compared to Baseline | 48 weeks | 
| Neuroimaging | Change in thalamic volume fraction at Week 48 compared to Baseline | 48 weeks | 
| Neuroimaging | Change in magnetization Transfer Saturation (MTSat) in cortex at Week 48 compared to Baseline | 48 weeks | 
| Neuroimaging | Change in T1 and T2 lesion volume at Week 48 compared to Baseline | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing Forms of Multiple Sclerosis, GNbAC1, Human Endogenous Retrovirus Type W, HERV-W, Temelimab