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

Phase 2

Completed

• Conditions: Multiple Sclerosis
• Interventions: Drug: temelimab 36 mg/kg; Drug: temelimab 54 mg/kg; Drug: temelimab 18 mg/kg; Drug: Placebo

• Registration Number: NCT04480307
• Lead Sponsor: GeNeuro Innovation SAS

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-06-17
• Study First Submitted: 2020-07-10
• Study First Submitted QC: 2020-07-20
• Study First Posted: 2020-07-21
• Primary Completion: 2022-01-24
• Study Completion: 2022-01-24
• Results First Submitted: 2024-03-22
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-23
• Last Update Submitted: 2024-08-23
• Results First Posted: 2024-11-07
• Last Update Posted: 2024-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
temelimab 36 mg/kg	temelimab 36 mg/kg	Monthly IV repeated dose
temelimab 54 mg/kg	temelimab 54 mg/kg	Monthly IV repeated dose
temelimab 18 mg/kg	temelimab 18 mg/kg	Monthly IV repeated dose
Placebo	Placebo	Monthly IV repeated dose

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	48 weeks	Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs)

Secondary Outcome Measures

Name	Time	Method
Neuroimaging	48 weeks	Change in thalamic volume fraction at Week 48 compared to Baseline. The thalamic volume fraction is the ratio of the legitimate (i.e. thalamic) brain tissue volume to the total volume within the brain surface contour.

Trial Locations

Locations (1)

Center for Neurology, Academic Specialist Center; 🇸🇪 Stockholm, Sweden