A Long-term Extension of Study GNC-401

• Status: Recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GeNeuro Innovation SAS

Criteria

Main Inclusion Criteria:

1. The patient has given written informed consent to participate in the study;

2. Current diagnosis of RMS, based on the McDonald 2017 criteria ;

3. Patients must have completed study GNC-401. Completion is defined as having performed the Week 48 assessments of study GNC 401;

4. 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;

5. 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

1. 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;

2. Body weight ≤40 kg;

3. Contraindication to continue rituximab therapy;

4. Has received rituximab less than 12 days prior to study entry;

5. Use of any of the following medications since Week 48 of the GNC 401 study:

1. Interferon (IFN) β, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide;

2. Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation;

3. Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine;

4. Any experimental drugs for the treatment of MS;

6. Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater lymphopenia (based on Week 48 of study GNC 401);

7. Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:

1. Diagnosis or history of schizophrenia;

2. Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation;

3. Current or past (within the last 2 years) alcohol or drug abuse;

8. 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);

9. Known inability to undergo an MRI scan;

10. Contraindications to the use of 5% glucose solution for infusion;

11. Inability to follow study instructions, or complete study assessments, as defined by the protocol;

12. 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;

13. Pregnant or breastfeeding women;

14. 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;