Clinical trial NCT05049161: A Long-term Extension of Study GNC-401
Official title: A Long-term Extension of Study GNC-401 With Temelimab in Patients With Relapsing Forms of Multiple Sclerosis (RMS) Under Treatment With Rituximab
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Relapsing Forms of Multiple Sclerosis
GNbAC1
Human Endogenous Retrovirus Type W
HERV-W
Temelimab
Lead sponsor: GeNeuro SA
Sponsor class: INDUSTRY
First posted: 2021-09-17
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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;

Primary outcomes:
measure: safety and tolerability:adverse event
timeFrame: 48 weeks
Secondary outcomes:
measure: Neuroimaging
timeFrame: 48 weeks
measure: Neuroimaging
timeFrame: 48 weeks
measure: Neuroimaging
timeFrame: 48 weeks
measure: Neuroimaging
timeFrame: 48 weeks
measure: Neuroimaging
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Center for Neurology, Academic Specialist Center
Study officials:
affiliation: GeNeuro Innovation SAS
name: David Leppert, MD
role: STUDY_DIRECTOR
References: