A Long-term Extension of Study GNC-401

GeNeuro

Status and phase: Terminated; Phase 2

Conditions: Multiple Sclerosis

Treatments: Drug: Temelimab 18 mg/kg; Drug: Temelimab 54 mg/kg; Drug: Temelimab 36mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05049161

GNC-402

2021-001973-21 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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33 participants in 3 patient groups

Temelimab 18 mg/kg

Experimental group

Description:

Monthly IV repeated dose

Treatment:

Drug: Temelimab 18 mg/kg

Temelimab 36 mg/kg

Experimental group

Description:

Monthly IV repeated dose

Treatment:

Drug: Temelimab 36mg/kg

Temelimab 54 mg/kg

Experimental group

Description:

Monthly IV repeated dose

Treatment:

Drug: Temelimab 54 mg/kg