Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled Phase IIa clinical study, assessing safety, tolerability, pharmacodynamic effects and pharmacokinetics of temelimab, administered at three different dose levels (18 mg/kg or 36 mg/kg or 54 mg/kg). In this study temelimab is administered subsequently to rituximab therapy, i.e. no co-administration of rituximab and temelimab is done in this study.

Official Title
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A Randomized, Double-Blind, Placebo Controlled Trial, Examining the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (RMS)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: temelimab 18 mg/kg
* Drug: temelimab 36 mg/kg
* Drug: temelimab 54 mg/kg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Current diagnosis of RMS, based on McDonald 2017 criteria Having received treatment with rituximab, as per local clinical routine for at least 12 months prior to the Screening Visit Having received their last dose of rituximab not more than 8 weeks and not less than 4 weeks before Randomization (Study Day 1) Having expanded disability status scale (EDSS) 2.5 - 5.5 inclusive at Screening Present clinical worsening in one or more neurological domains as assessed by EDSS, ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by SDMT or increased need of walking aids or pharmacological/procedures for bowel and bladder functions over the last year. Main Exclusion Criteria: Current diagnosis of primary progressive MS (PPMS) Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could better explain the patient's signs and symptoms Usage of any of the following medications prior to the Screening visit: Any usage of interferon beta, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide within 12 months prior to Screening, Any history of exposure to mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation at any time, Any usage of natalizumab within 24 months prior to Screening, Any usage of highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine within 12 months prior to Screening, Any usage of any experimental treatment if not washed out for ≥ 5 half-lives or ≥ 12 months (whichever is longer), except rituximab which is allowed before the study. CTCAE Grade 2 or greater lymphopenia Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study 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 (NYHA class 3 or 4) 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

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 36 mg/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>|
| Placebo Comparator: Placebo<br>Monthly IV repeated dose | Drug: Placebo<br>* Placebo 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 | To determine if temelimab treatment is associated with an increase of adverse event | 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 (MTR) in periventricular NAWM 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 (MTR) 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