MedPath

RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.

Phase 3
Completed
Conditions
Multiple Sclerosis, Relapsing-Remitting
Interventions
Registration Number
NCT02746744
Lead Sponsor
Anders Svenningsson
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
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.

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sodium Chloride solutionSodium Chloride solutionSham infusion with sodium chloride solution for the Tecfidera/Dimethyl Fumarate arm every 6 months (so that the examining physician will be blinded)
Dimethyl FumarateSodium Chloride solutionIntake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
RituximabRituximabInfusion of Mabthera/Rituximab every 6 months
Dimethyl FumarateDimethyl fumarateIntake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Sodium Chloride solutionDimethyl fumarateSham infusion with sodium chloride solution for the Tecfidera/Dimethyl Fumarate arm every 6 months (so that the examining physician will be blinded)
Primary Outcome Measures
NameTimeMethod
Freedom of relapseWithin 2 years

The relative risk of experiencing a relapse during the two-year period for either compound.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (17)

Fredrik Piehl

🇸🇪

Stockholm, Sweden

South Älvsborg Hospital

🇸🇪

Borås, Sweden

Falun Hospital

🇸🇪

Falun, Sweden

Gävle Hospital

🇸🇪

Gävle, Sweden

Saghlgrenska Hospital

🇸🇪

Göteborg, Sweden

Helsingborg Hospital

🇸🇪

Helsingborg, Sweden

Karlstad Hospital

🇸🇪

Karlstad, Sweden

Halland Hospital Kungsbacka

🇸🇪

Kungsbacka, Sweden

Linköping University Hospital

🇸🇪

Linköping, Sweden

Capio StGöran Hospital

🇸🇪

Stockholm, Sweden

Danderyd hospital

🇸🇪

Stockholm, Sweden

Karolinska Hospital Huddinge

🇸🇪

Stockholm, Sweden

Umeå University

🇸🇪

Umeå, Sweden

Uppsala Academiska Hospital

🇸🇪

Uppsala, Sweden

Örebro University Hospital

🇸🇪

Örebro, Sweden

Östersund Hospital

🇸🇪

Östersund, Sweden

Nyköping Hospital

🇸🇪

Nyköping, Sweden

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