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

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ClinicalTrials.gov Identifier: NCT02746744
Recruitment Status : Completed
First Posted : April 21, 2016
Last Update Posted : October 12, 2021
Sponsor:
Information provided by (Responsible Party):
Anders Svenningsson, Karolinska Institutet

Tracking Information
First Submitted Date  ICMJE April 18, 2016
First Posted Date  ICMJE April 21, 2016
Last Update Posted Date October 12, 2021
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2017)
Freedom of relapse [ Time Frame: Within 2 years ]
The relative risk of experiencing a relapse during the two-year period for either compound.
Original Primary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
The relative risk of experiencing a relapse during the two-year period for either compound. [ Time Frame: Within 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Relapsing-Remitting
Intervention  ICMJE
  • Drug: Rituximab
    Infusion of Mabthera/Rituximab every 6 months
    Other Name: Mabthera
  • Drug: Dimethyl fumarate
    Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
    Other Name: 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 Name: Sodium Chloride
Study Arms  ICMJE
  • Experimental: Rituximab
    Infusion of Mabthera/Rituximab every 6 months
    Intervention: Drug: Rituximab
  • Active Comparator: Dimethyl Fumarate
    Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
    Interventions:
    • Drug: Dimethyl fumarate
    • Drug: Sodium Chloride solution
  • 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)
    Interventions:
    • Drug: Dimethyl fumarate
    • Drug: Sodium Chloride solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 18, 2016)
200
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2021
Actual Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02746744
Other Study ID Numbers  ICMJE EudraCT 2015-004116-38
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anders Svenningsson, Karolinska Institutet
Study Sponsor  ICMJE Anders Svenningsson
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anders Svenningsson, MD, PhD Dept.of Medicine, Sect.of Neurology, Danderyd Hospital
PRS Account Karolinska Institutet
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP