RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis. (RIFUND-MS)

October 11, 2021 updated by: Anders Svenningsson

RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis. A Randomized Phase 3 Study Comparing Rituximab With Dimethyl Fumarate in Early Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Borås, Sweden
        • South Älvsborg Hospital
      • Falun, Sweden
        • Falun Hospital
      • Gävle, Sweden
        • Gävle hospital
      • Göteborg, Sweden
        • Saghlgrenska Hospital
      • Helsingborg, Sweden
        • Helsingborg Hospital
      • Karlstad, Sweden
        • Karlstad hospital
      • Kungsbacka, Sweden
        • Halland Hospital Kungsbacka
      • Linköping, Sweden
        • Linköping University Hospital
      • Nyköping, Sweden
        • Nyköping Hospital
      • Stockholm, Sweden
        • Danderyd Hospital
      • Stockholm, Sweden
        • Fredrik Piehl
      • Stockholm, Sweden
        • Capio StGöran Hospital
      • Stockholm, Sweden
        • Karolinska Hospital Huddinge
      • Umeå, Sweden
        • Umeå University
      • Uppsala, Sweden
        • Uppsala Academiska Hospital
      • Örebro, Sweden
        • Orebro University Hospital
      • Östersund, Sweden
        • Östersund Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab
Infusion of Mabthera/Rituximab every 6 months
Drug: Rituximab
Infusion of Mabthera/Rituximab every 6 months
Other Names:
  • Mabthera
Active Comparator: Dimethyl Fumarate
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Drug: Dimethyl fumarate
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Other Names:
  • Tecfidera
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
Other Names:
  • Sodium Chloride
Sham Comparator: 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)
Drug: Dimethyl fumarate
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Other Names:
  • Tecfidera
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
Other Names:
  • Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom of relapse
Time Frame: Within 2 years
The relative risk of experiencing a relapse during the two-year period for either compound.
Within 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anders Svenningsson

Investigators

  • Principal Investigator: Anders Svenningsson, MD, PhD, Dept.of Medicine, Sect.of Neurology, Danderyd Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2016

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

April 18, 2016

First Submitted That Met QC Criteria

April 18, 2016

First Posted (Estimate)

April 21, 2016

Study Record Updates

Last Update Posted (Actual)

October 12, 2021

Last Update Submitted That Met QC Criteria

October 11, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT 2015-004116-38

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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