Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (ProTEct-MS)

A Randomized, Double-Blind, Placebo Controlled Trial, Examining the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (RMS)

Randomized, double-blind, placebo-controlled Phase IIa clinical study, assessing safety, tolerability, pharmacodynamic effects and pharmacokinetics of temelimab, administered at three different dose levels (18 mg/kg or 36 mg/kg or 54 mg/kg).

In this study temelimab is administered subsequently to rituximab therapy, i.e. no co-administration of rituximab and temelimab is done in this study.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: temelimab 18 mg/kg; Drug: temelimab 36 mg/kg; Drug: temelimab 54 mg/kg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• 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

Description

Main Inclusion Criteria:

• Current diagnosis of RMS, based on McDonald 2017 criteria
• Having received treatment with rituximab, as per local clinical routine for at least 12 months prior to the Screening Visit
• Having received their last dose of rituximab not more than 8 weeks and not less than 4 weeks before Randomization (Study Day 1)
• Having expanded disability status scale (EDSS) 2.5 - 5.5 inclusive at Screening
• Present clinical worsening in one or more neurological domains as assessed by EDSS, ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by SDMT or increased need of walking aids or pharmacological/procedures for bowel and bladder functions over the last year.

Main Exclusion Criteria:

• Current diagnosis of primary progressive MS (PPMS)
• Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could better explain the patient's signs and symptoms

• Usage of any of the following medications prior to the Screening visit:

  • Any usage of interferon beta, glatiramer acetate, IV immunoglobulin (IVIG), dimethyl fumarate or teriflunomide within 12 months prior to Screening,
  • Any history of exposure to mitoxantrone, cladribine, alemtuzumab, cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or bone marrow transplantation at any time,
  • Any usage of natalizumab within 24 months prior to Screening,
  • Any usage of highly potent immune modulating therapy, such as: ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy, plasmapheresis or azathioprine within 12 months prior to Screening,
  • Any usage of any experimental treatment if not washed out for ≥ 5 half-lives or ≥ 12 months (whichever is longer), except rituximab which is allowed before the study.
• CTCAE Grade 2 or greater lymphopenia
• Any major medical or psychiatric disorder that would affect the capacity of the patient to fulfill the requirements of the study
• 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)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

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 36 mg/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).
Placebo Comparator: Placebo; Monthly IV repeated dose	Drug: Placebo; Placebo 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	Analysis of Adverse Events (AEs) focused on Treatment Emergent AEs (TEAEs)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroimaging	Change in T1 and T2 lesion volume at Week 48 compared to Baseline	48 weeks
Neuroimaging	Change in magnetization transfer saturation (MT Sat) in periventricular NAWM at Week 48 compared to Baseline. The MT Sat represents the fraction of free water, as transformed to per-unit scale, saturated by a single Magnetization transfer (MT) pulse during repetition time (TR).	48 weeks
Neuroimaging	Change in magnetization transfer saturation (MT Sat) in cortex at Week 48 compared to Baseline. The MT Sat represents the fraction of free water, as transformed to per-unit scale, saturated by a single Magnetization transfer pulse during repetition time.	48 weeks
Neuroimaging	Change in brain parenchymal volume fraction at Week 48 compared to Baseline. The brain parenchymal fraction is defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour.	48 weeks
Neuroimaging	Change in thalamic volume fraction at Week 48 compared to Baseline. The thalamic volume fraction is the ratio of the legitimate (i.e. thalamic) brain tissue volume to the total volume within the brain surface contour.	48 weeks

Collaborators and Investigators

• Sponsor: GeNeuro Innovation SAS
• Investigators: Study Director: David Leppert, MD, GeNeuro Innovation SAS

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2020
• Primary Completion (Actual): January 24, 2022
• Study Completion (Actual): January 24, 2022

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: August 23, 2024
• Last Verified: August 1, 2024

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: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: GNC-401; 2019-004822-15 (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