Non-inferiority Study of Rituximab Compared to Ocrelizumab in Relapsing MS

NCT05834855 | Recruiting Phase 3 DMC

• 1 other identifier: Anti-CD20 in RMS
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Ocrelizumab is widely and effectively used to treat relapsing multiple sclerosis (RMS). Phase II studies and data from large patient cohorts indicate that rituximab, another anti-CD20 monoclonal antibody, is probably equally effective and safe as ocrelizumab in the treatment of RMS. An advantage of rituximab is a considerably lower price. Therefore we will start a study aimed at demonstrating non-inferiority of rituximab compared to ocrelizumab in RMS. If non-inferiority of rituximab can be shown, important reductions in the cost of treatment of RMS will be possible, without loss of efficacy. Objective: Evaluating the efficacy and safety of ritixumab compared to ocrelizumab in the treatmens of RMS. Study design: Randomized double blind multi-centre non-inferiority study of rituximab compared to ocrelizumab in 200 patients with RMS. The trial duration will be 30 months Study population: The study population consists of 200 adult RMS patiens with an indication to start anti-CD20 monoclonal antibody treatment. Intervention: Patients will be randomized 1:1 into the standard group (ocrelizumab treatment) or the experimental group (rituximab treatment). Main study parameters: To conclude non-inferiority of rituximab there will be one primary endpoint: the proportion of patients free of inflammatory disease activity (defined as: new or enlarged T2 lesions) between week 24 (M6) and week 96 (M24) of treatment in each arm. Secondary trial endpoints are presence and number of clinical relapses,T2 and contrast enhancing lesion volumes, brain volume and brain volume changes, disease progression (defined as clinically relevant change on any of the measures: EDSS, T25FW, 9HPT, SDMT), biochemical parameters such as lipidomics and neurofilament light (NfL), immunological parameters, safety as measured by the number of (serious) adverse events ((S)AE), quality of life (EQ-5D-L) and treatment satisfaction (TSQM) and patient reported measures of MS impact (MSIS-29) and well-being (questionnaire on physical complaints) Nature and extent of the burden and risk: Patients included in this study will be treated and monitored by MRI, clinical tests and laboratory tests according to existing protocols and will not be exposed to extra or unknown risks. They will have extra annual questionnaires and larger blood samples at some time points. There is extensive experience with both rituximab and ocrelizumab as efficacious and safe treatments of RMS.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases

Keywords

ocrelizumab; rituximab; non-inferiority

Outcome Measures

Primary Outcomes (1)

• Proportion of patients free of inflammatory disease activity

  Proportion of patients with no new or enlarged T2 lesions on brain MRI between month 6 and month 24

  between month 6 and month 24

Secondary Outcomes (7)

• Presence and number of clinical relapses

  Baseline, month 6, month 24

• Contrast enhancing lesions

  Baseline, month 6, month 24

• Average number of T2 lesions on brain MRI

  Baseline, month 6, month 24

• Disability progression during follow-up

  Baseline, month 6, month 24

• Disability progression during follow-up

  Baseline, month 6, month 24

Other Outcomes (16)

• Anti-drug antibodies

  30 months

• Infusion reactions

  30 months

• Infections

  30 months

Study Arms (2)

Ocrelizumab

NO INTERVENTION

The standard group will receive ocrelizumab (600 mg, the first dosage given in two infusion of 300 mg with a two week interval) following the current treatment protocol

Rituximab

EXPERIMENTAL

The experimental group will receive rituximab (1000 mg). Rituximab will be given intravenously. To ensure blinding of treatment allocation two dosages of 500 mg with a two week interval will be given instead of one initial dosage of 1000 mg of rituximab to mimic the ocrelizumab protocol

Drug: Rituximab

Interventions

Rituximab DRUG

Treatment with rituximab

Also known as: MabThera, Truxima, Ruxience, Rixathon

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18 years and older
• A diagnosis of relapsing MS according to the 2017 revised diagnostic criteria
• Indication to start treatment with anti-CD20 therapy according to the treating neurologist and the relevant label in the Netherlands for treatment of relapsing MS
• Able to understand written and spoken Dutch or English
• Capable of giving signed informed consent including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Screening EDSS score ≤ 6.5 .

You may not qualify if:

• Medical Conditions
• A known allergy or other intolerability to RTX, OCR, gadolinium-based MRI contrast agents, or corticosteroids.
• A diagnosis of primary progressive MS according to the diagnostic criteria.
• A diagnosis of not-active secondary progressive MS.
• Chronic infectious diseases such as tuberculosis, VZV, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit.
• A history of proven inflammatory bowel disease such as M. Crohn or ulcerative colitis
• Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
• Cardiac disease that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC
• Active malignancy or prior history of malignancy that makes treatment with OCR or RTX contra-indicated as stated by the most recent SmPC.
• WBC \< 1.5 x 109/L if not caused by a reversible effect of documented ongoing medication. If caused by a reversible effect of documented ongoing medication the WBC count must be \> 1,5 x 109/L before start of study treatment.
• Platelet (thrombocyte) count \< 100 x 109/L
• ALAT and/or ASAT more than 2 times the upper normal reference limit (ULN)
• Serum creatinine \> 200 μmol/L
• Serum bilirubin \> ULN
• Serum IgG \< LLN

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Stichting Treatmeds: collaborator

Study Sites (1)

Amsterdam UMC, location VUmc

Amsterdam, 1081 HV, Netherlands

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Leukoencephalopathies; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bob van Oosten, Dr

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Schoof, Msc

CONTACT

650087853; l.g.schoof@amsterdamumc.nl

Eva Strijbis, Dr.

CONTACT

204442182; e.strijbis@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patient, site personnel administrating infusions, and the treating and evaluating neurologist and study nurse will all be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Multicenter randomized controlled double-blind non-inferiority trial in The Netherlands

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: April 28, 2023
• Study Start: April 1, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 28, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After medical ethical commitee approved the study protocol

Locations

NL (1)