A Long-term Extension of Study GNC-401
Primary Purpose
Multiple Sclerosis
Status
Terminated
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Temelimab 18 mg/kg
Temelimab 36mg/kg
Temelimab 54 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Relapsing Forms of Multiple Sclerosis, GNbAC1, Human Endogenous Retrovirus Type W, HERV-W, Temelimab
Eligibility Criteria
Main Inclusion Criteria:
- The patient has given written informed consent to participate in the study;
- Current diagnosis of RMS, based on the McDonald 2017 criteria ;
- Patients must have completed study GNC-401. Completion is defined as having performed the Week 48 assessments of study GNC 401;
- 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;
- 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
- 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;
- Body weight ≤40 kg;
- Contraindication to continue rituximab therapy;
- Has received rituximab less than 12 days prior to study entry;
Use of any of the following medications since Week 48 of the GNC 401 study:
- Interferon (IFN) β, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide;
- Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation;
- Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine;
- Any experimental drugs for the treatment of MS;
- Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater lymphopenia (based on Week 48 of study GNC 401);
Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:
- Diagnosis or history of schizophrenia;
- Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation;
- Current or past (within the last 2 years) alcohol or drug abuse;
- 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);
- Known inability to undergo an MRI scan;
- Contraindications to the use of 5% glucose solution for infusion;
- Inability to follow study instructions, or complete study assessments, as defined by the protocol;
- 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;
- Pregnant or breastfeeding women;
- 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;
Sites / Locations
- Center for Neurology, Academic Specialist Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Temelimab 18 mg/kg
Temelimab 36 mg/kg
Temelimab 54 mg/kg
Arm Description
Monthly IV repeated dose
Monthly IV repeated dose
Monthly IV repeated dose
Outcomes
Primary Outcome Measures
safety and tolerability:adverse event
Number of Patients With Treatment-Related Adverse Events
Secondary Outcome Measures
Neuroimaging
Change in Brain parenchymal volume fraction at Week 48 compared to Baseline
Neuroimaging
change in magnetization transfer Saturation (MTSat) in periventricular NAWM at at Week 48 compared to Baseline
Neuroimaging
Change in thalamic volume fraction at Week 48 compared to Baseline
Neuroimaging
Change in magnetization Transfer Saturation (MTSat) in cortex at Week 48 compared to Baseline
Neuroimaging
Change in T1 and T2 lesion volume at Week 48 compared to Baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05049161
Brief Title
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
Drug product unavailability
Study Start Date
August 27, 2021 (Actual)
Primary Completion Date
May 18, 2022 (Actual)
Study Completion Date
May 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GeNeuro Innovation SAS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Relapsing Forms of Multiple Sclerosis, GNbAC1, Human Endogenous Retrovirus Type W, HERV-W, Temelimab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Temelimab 18 mg/kg
Arm Type
Experimental
Arm Description
Monthly IV repeated dose
Arm Title
Temelimab 36 mg/kg
Arm Type
Experimental
Arm Description
Monthly IV repeated dose
Arm Title
Temelimab 54 mg/kg
Arm Type
Experimental
Arm Description
Monthly IV repeated dose
Intervention Type
Drug
Intervention Name(s)
Temelimab 18 mg/kg
Intervention Description
temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
Intervention Type
Drug
Intervention Name(s)
Temelimab 36mg/kg
Intervention Description
temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
Intervention Type
Drug
Intervention Name(s)
Temelimab 54 mg/kg
Intervention Description
temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total)
Primary Outcome Measure Information:
Title
safety and tolerability:adverse event
Description
Number of Patients With Treatment-Related Adverse Events
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Neuroimaging
Description
Change in Brain parenchymal volume fraction at Week 48 compared to Baseline
Time Frame
48 weeks
Title
Neuroimaging
Description
change in magnetization transfer Saturation (MTSat) in periventricular NAWM at at Week 48 compared to Baseline
Time Frame
48 weeks
Title
Neuroimaging
Description
Change in thalamic volume fraction at Week 48 compared to Baseline
Time Frame
48 weeks
Title
Neuroimaging
Description
Change in magnetization Transfer Saturation (MTSat) in cortex at Week 48 compared to Baseline
Time Frame
48 weeks
Title
Neuroimaging
Description
Change in T1 and T2 lesion volume at Week 48 compared to Baseline
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
The patient has given written informed consent to participate in the study;
Current diagnosis of RMS, based on the McDonald 2017 criteria ;
Patients must have completed study GNC-401. Completion is defined as having performed the Week 48 assessments of study GNC 401;
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;
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
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;
Body weight ≤40 kg;
Contraindication to continue rituximab therapy;
Has received rituximab less than 12 days prior to study entry;
Use of any of the following medications since Week 48 of the GNC 401 study:
Interferon (IFN) β, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide;
Natalizumab, mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation;
Highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine;
Any experimental drugs for the treatment of MS;
Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater lymphopenia (based on Week 48 of study GNC 401);
Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study, including:
Diagnosis or history of schizophrenia;
Current diagnosis of moderate to severe bipolar disorder, major depressive disorder, major depressive episode, history of suicide attempt, or current suicidal ideation;
Current or past (within the last 2 years) alcohol or drug abuse;
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);
Known inability to undergo an MRI scan;
Contraindications to the use of 5% glucose solution for infusion;
Inability to follow study instructions, or complete study assessments, as defined by the protocol;
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;
Pregnant or breastfeeding women;
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Leppert, MD
Organizational Affiliation
GeNeuro Innovation SAS
Official's Role
Study Director
Facility Information:
Facility Name
Center for Neurology, Academic Specialist Center
City
Stockholm
ZIP/Postal Code
113 65
Country
Sweden
12. IPD Sharing Statement
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A Long-term Extension of Study GNC-401
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