A Long-term Extension of Study GNC-401
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Temelimab 18 mg/kg Monthly IV repeated dose |
Drug: Temelimab 18 mg/kg
temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
|
Experimental: Temelimab 36 mg/kg Monthly IV repeated dose |
Drug: Temelimab 36mg/kg
temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
|
Experimental: Temelimab 54 mg/kg Monthly IV repeated dose |
Drug: Temelimab 54 mg/kg
temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
|
Outcome Measures
Primary Outcome Measures
- safety and tolerability:adverse event [48 weeks]
Number of Patients With Treatment-Related Adverse Events
Secondary Outcome Measures
- Neuroimaging [48 weeks]
Change in Brain parenchymal volume fraction at Week 48 compared to Baseline
- Neuroimaging [48 weeks]
change in magnetization transfer Saturation (MTSat) in periventricular NAWM at at Week 48 compared to Baseline
- Neuroimaging [48 weeks]
Change in thalamic volume fraction at Week 48 compared to Baseline
- Neuroimaging [48 weeks]
Change in magnetization Transfer Saturation (MTSat) in cortex at Week 48 compared to Baseline
- Neuroimaging [48 weeks]
Change in T1 and T2 lesion volume at Week 48 compared to Baseline
Eligibility Criteria
Criteria
Main Inclusion Criteria:
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The patient has given written informed consent to participate in the study;
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Current diagnosis of RMS, based on the McDonald 2017 criteria ;
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Patients must have completed study GNC-401. Completion is defined as having performed the Week 48 assessments of study GNC 401;
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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;
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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
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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;
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Body weight ≤40 kg;
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Contraindication to continue rituximab therapy;
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Has received rituximab less than 12 days prior to study entry;
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Use of any of the following medications since Week 48 of the GNC 401 study:
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Interferon (IFN) β, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide;
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Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation;
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Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine;
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Any experimental drugs for the treatment of MS;
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Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater lymphopenia (based on Week 48 of study GNC 401);
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Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:
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Diagnosis or history of schizophrenia;
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Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation;
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Current or past (within the last 2 years) alcohol or drug abuse;
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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);
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Known inability to undergo an MRI scan;
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Contraindications to the use of 5% glucose solution for infusion;
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Inability to follow study instructions, or complete study assessments, as defined by the protocol;
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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;
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Pregnant or breastfeeding women;
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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;
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Center for Neurology, Academic Specialist Center | Stockholm | Sweden | 113 65 |
Sponsors and Collaborators
- GeNeuro Innovation SAS
Investigators
- Study Director: David Leppert, MD, GeNeuro Innovation SAS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GNC-402
- 2021-001973-21