Extension of Study GNC-401 with temelimab in patients with Multiple Sclerosis under treatment with rituximab
- Conditions
- Multiple SclerosisMedDRA version: 21.0Level: PTClassification code 10080700Term: Relapsing multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-001973-21-SE
- Lead Sponsor
- GeNeuro Innovation SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
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 10E9 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 10E9 CD19 cells/L);
6. Be willing and able to follow all study procedures and assessments according to the study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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:
a. IFN-ß, glatiramer acetate, IVIG, dimethyl fumarate or teriflunomide;
b. Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide,
systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation;
c. Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine;
d. Any experimental drugs for the treatment of MS;
6. 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:
a. Diagnosis or history of schizophrenia;
b. Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation;
c. 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 (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. Legal incapacity or limited legal capacity;
14. Pregnant or breastfeeding women;
15. Abnormal liver function tests: AST or ALT >2 times ULN, or conjugated bilirubin >2 times ULN, or AP or GGT >3 times ULN;
16. FPCBP or PMP, not willing to use highly effective contraceptive methods throughout the study duration and for at least 5 months after the last study treatment. The Investigator must inform the participant about the risks of not using an effective method of birth control during the course of the study and they should discuss with
the participant the most appropriate method.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to assess the long-term safety and tolerability of temelimab in patients with RMS who are treated with rituximab.;Secondary Objective: The secondary objective is to determine the PD effects of temelimab on neuroprotection and remyelination based on neuroimaging.;Primary end point(s): Incidence (number and % of patients) of adverse events (AEs) and serious adverse events (SAEs) during the 48-week study.;Timepoint(s) of evaluation of this end point: Over 48 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Change in magnetization transfer saturation (MTSat) in<br>periventricular NAWM at Week 48 compared to baseline;<br>- Change in MTSat in cerebral cortex at Week 48 compared to<br>baseline;<br>- Change in T1 lesion volume at Week 48 compared to baseline;<br>- Change in T2 lesion volume at Week 48 compared to baseline;<br>- Change in brain parenchymal volume fraction at Week 48<br>compared to baseline;<br>- Change in thalamic volume fraction at Week 48 compared to<br>baseline.;Timepoint(s) of evaluation of this end point: At Week 48