a long-term extension of study gnc-401

Conditions: Multiple Sclerosis

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;

Keywords: relapsing forms of multiple sclerosis gnbac1 human endogenous retrovirus type w herv-w temelimab