RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.

NCT ID: NCT02746744

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2021-08-31

Brief Summary

A randomized phase 3 study comparing Rituximab with Dimethyl Fumarate in early Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome.

Detailed Description

This is a prospective randomised phase 3 study comparing a novel treatment protocol of Rituximab with a present first line disease modifying drug regarding both clinical, radiological and biochemical parameters. This will be measured via clinical investigations, MRI and Cerebrospinal fluid analyses. Each patient will have one treating physician responsible for all ongoing medical questions and decisions regarding continuation in the study and one examining physician performing the blinded Expanded Disability Status Scale examination and assessments of exacerbations. The coordinating nurse will administer the study-related tests and administer the rituximab infusions. In order to keep the examining physician blinded the patients receiving disease modifying drug will receive infusions with sodium chloride solution at the same interval as the rituximab arm is receiving. In both instances an opaque cover bag will shield the content of the infusion solution. In this case the examining physician will not be able to identify rituximab patients in case of accidental meetings on the neurology unit.

Randomisation will be performed via a randomisation module in the national Swedish MS registry. The patients will be randomised in a 1:1 ratio and receive their treatments in accordance with clinical practice. Thus, the study will mimic the real-life situation in which the treatments will be administered which involves both positive and negative consequences. As positive consequence the result of the study will have a high degree of validity in relation to expected outcome in clinical practice. As negative consequence there may be psychological effects of knowing which medication one is receiving. Since both drugs probably are perceived as positive treatment options in MS today it is unlikely that there will be a predominant placebo effect of either of the treatment options.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Rituximab

Infusion of Mabthera/Rituximab every 6 months

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Infusion of Mabthera/Rituximab every 6 months

Dimethyl Fumarate

Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.

Group Type: ACTIVE_COMPARATOR

Dimethyl fumarate

Intervention Type: DRUG

Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.

Sodium Chloride solution

Intervention Type: DRUG

Placebo/Sham infusion every 6 months so that the examining physician (blinded) should not know which patient gets Mabthera or Tecfidera

Sodium Chloride solution

Sham infusion with sodium chloride solution for the Tecfidera/Dimethyl Fumarate arm every 6 months (so that the examining physician will be blinded)

Group Type: SHAM_COMPARATOR

Dimethyl fumarate

Intervention Type: DRUG

Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.

Sodium Chloride solution

Intervention Type: DRUG

Placebo/Sham infusion every 6 months so that the examining physician (blinded) should not know which patient gets Mabthera or Tecfidera

Interventions

Rituximab

Infusion of Mabthera/Rituximab every 6 months

Intervention Type: DRUG

Dimethyl fumarate

Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.

Intervention Type: DRUG

Sodium Chloride solution

Placebo/Sham infusion every 6 months so that the examining physician (blinded) should not know which patient gets Mabthera or Tecfidera

Intervention Type: DRUG

Other Intervention Names

Mabthera; Tecfidera; Sodium Chloride

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Relapsing Remitting MS according to the 2017 revised McDonald cri-teria 27 OR one demyelinating episode in conjunction with at least one asympto-matic high intensity T2 lesion with size and location compatible with MS.
• Untreated OR treated with first-line injectables (interferon or glatiramer acetate)
• Between the age of 18 and 50 years (inclusive) of age
• No more than ten years of disease duration
• During the previous year, clinical or radiological disease activity defined as at least one of the following:

• ≥ 1 relapse
• ≥ 2 T2 lesions
• ≥ 1 Gd+ lesions
• Expanded Disability Status Scale: 0 - 5,5 (inclusive)
• In fertile females, willing to comply with effective contraceptive methods. These include birth control pills, surgical sterilization of patient or partner or intrauterine device. Non-fertile women is defined as more than 12 months of amenorrhea without an alternative medical cause or, in case of ambiguities, an follicle stimulation hormone level in the postmenopausal range.

Exclusion Criteria

• Diagnosis of Progressive MS
• Pregnant or lactating women: human chorionic gonadotropin (s-HCG) will be tested on all women at screening, before each study-related infusion and in any situation where there is a reason to suspect pregnancy during the trial, eg delayed menstrual period more than five days above expected time.
• Patients having contraindication for or otherwise not compliant with MRI investigations
• Simultaneous treatment with other immunosuppressive drugs
• Active, severe infections Signs of infections are assessed before inclusion and each study-related infusion through clinical examination and further evaluated by laboratory and other relevant investigations in case of suspected ongoing infection. Hepatitis serology (HBsAg and anti-HBc) will be evaluated before treatment onset.
• Severe cardiac disorder, eg signs of congestive heart failure or coronary artery disease. This will be evaluated through clinical assessment before inclusion.
• Vaccination within 4 weeks of first dose of study medication.
• Documented allergy or intolerance to any of the investigational products.
• Severe psychiatric condition

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anders Svenningsson

OTHER

Sponsor Role: lead

Responsible Party

Anders Svenningsson

MD PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anders Svenningsson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept.of Medicine, Sect.of Neurology, Danderyd Hospital

Locations

South Älvsborg Hospital

Borås, , Sweden

Falun Hospital

Falun, , Sweden

Gävle Hospital

Gävle, , Sweden

Saghlgrenska Hospital

Gothenburg, , Sweden

Helsingborg Hospital

Helsingborg, , Sweden

Karlstad Hospital

Karlstad, , Sweden

Halland Hospital Kungsbacka

Kungsbacka, , Sweden

Linköping University Hospital

Linköping, , Sweden

Nyköping Hospital

Nyköping, , Sweden

Örebro University Hospital

Örebro, , Sweden

Östersund Hospital

Östersund, , Sweden

Capio StGöran Hospital

Stockholm, , Sweden

Danderyd hospital

Stockholm, , Sweden

Fredrik Piehl

Stockholm, , Sweden

Karolinska Hospital Huddinge

Stockholm, , Sweden

Umeå University

Umeå, , Sweden

Uppsala Academiska Hospital

Uppsala, , Sweden

Countries

Sweden

References

Svenningsson A, Frisell T, Burman J, Salzer J, Fink K, Hallberg S, Hambraeus J, Axelsson M, Nimer FA, Sundstrom P, Gunnarsson M, Johansson R, Mellergard J, Rosenstein I, Ayad A, Sjoblom I, Risedal A, de Flon P, Gilland E, Lindeberg J, Shawket F, Piehl F, Lycke J. Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial. Lancet Neurol. 2022 Aug;21(8):693-703. doi: 10.1016/S1474-4422(22)00209-5.

Reference Type: DERIVED

PMID: 35841908 (View on PubMed)

Other Identifiers

EudraCT 2015-004116-38

Identifier Type: -

Identifier Source: org_study_id