A Long-term Extension of Study GNC-401

A Long-term Extension of Study GNC-401 With Temelimab in Patients With Relapsing Forms of Multiple Sclerosis (RMS) Under Treatment With Rituximab

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Temelimab 18 mg/kg; Drug: Temelimab 36mg/kg; Drug: Temelimab 54 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 113 65
    • Center for Neurology, Academic Specialist Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability:adverse event	Number of Patients With Treatment-Related Adverse Events	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroimaging	Change in thalamic volume fraction at Week 48 compared to Baseline	48 weeks
Neuroimaging	Change in T1 and T2 lesion volume at Week 48 compared to Baseline	48 weeks
Neuroimaging	Change in Brain parenchymal volume fraction at Week 48 compared to Baseline	48 weeks
Neuroimaging	change in magnetization transfer Saturation (MTSat) in periventricular NAWM at at Week 48 compared to Baseline	48 weeks
Neuroimaging	Change in magnetization Transfer Saturation (MTSat) in cortex at Week 48 compared to Baseline	48 weeks

Collaborators and Investigators

• Sponsor: GeNeuro Innovation SAS

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 27, 2021
• Primary Completion (ACTUAL): May 18, 2022
• Study Completion (ACTUAL): May 18, 2022

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (ACTUAL): September 17, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Relapsing Forms of Multiple Sclerosis; GNbAC1; Human Endogenous Retrovirus Type W; HERV-W; Temelimab
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: GNC-402; 2021-001973-21 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No