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

Primary Purpose

Multiple Sclerosis, Relapsing-Remitting

Status
Completed
Phase
Phase 3
Locations
Sweden
Study Type
Interventional
Intervention
Rituximab
Dimethyl fumarate
Sodium Chloride solution
Sponsored by
Anders Svenningsson
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Sham Comparator

Arm Label

Rituximab

Dimethyl Fumarate

Sodium Chloride solution

Arm Description

Infusion of Mabthera/Rituximab every 6 months

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
April 18, 2016
Last Updated
October 11, 2021
Sponsor
Anders Svenningsson
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1. Study Identification

Unique Protocol Identification Number
NCT02746744
Brief Title
RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.
Acronym
RIFUND-MS
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
July 2021 (Actual)
Study Completion Date
August 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Anders Svenningsson

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Infusion of Mabthera/Rituximab every 6 months
Arm Title
Dimethyl Fumarate
Arm Type
Active Comparator
Arm Description
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Arm Title
Sodium Chloride solution
Arm Type
Sham Comparator
Arm Description
Sham infusion with sodium chloride solution for the Tecfidera/Dimethyl Fumarate arm every 6 months (so that the examining physician will be blinded)
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Mabthera
Intervention Description
Infusion of Mabthera/Rituximab every 6 months
Intervention Type
Drug
Intervention Name(s)
Dimethyl fumarate
Other Intervention Name(s)
Tecfidera
Intervention Description
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
Intervention Type
Drug
Intervention Name(s)
Sodium Chloride solution
Other Intervention Name(s)
Sodium Chloride
Intervention Description
Placebo/Sham infusion every 6 months so that the examining physician (blinded) should not know which patient gets Mabthera or Tecfidera
Primary Outcome Measure Information:
Title
Freedom of relapse
Description
The relative risk of experiencing a relapse during the two-year period for either compound.
Time Frame
Within 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anders Svenningsson, MD, PhD
Organizational Affiliation
Dept.of Medicine, Sect.of Neurology, Danderyd Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
South Älvsborg Hospital
City
Borås
Country
Sweden
Facility Name
Falun Hospital
City
Falun
Country
Sweden
Facility Name
Gävle Hospital
City
Gävle
Country
Sweden
Facility Name
Saghlgrenska Hospital
City
Göteborg
Country
Sweden
Facility Name
Helsingborg Hospital
City
Helsingborg
Country
Sweden
Facility Name
Karlstad Hospital
City
Karlstad
Country
Sweden
Facility Name
Halland Hospital Kungsbacka
City
Kungsbacka
Country
Sweden
Facility Name
Linköping University Hospital
City
Linköping
Country
Sweden
Facility Name
Nyköping Hospital
City
Nyköping
Country
Sweden
Facility Name
Capio StGöran Hospital
City
Stockholm
Country
Sweden
Facility Name
Danderyd hospital
City
Stockholm
Country
Sweden
Facility Name
Fredrik Piehl
City
Stockholm
Country
Sweden
Facility Name
Karolinska Hospital Huddinge
City
Stockholm
Country
Sweden
Facility Name
Umeå University
City
Umeå
Country
Sweden
Facility Name
Uppsala Academiska Hospital
City
Uppsala
Country
Sweden
Facility Name
Örebro University Hospital
City
Örebro
Country
Sweden
Facility Name
Östersund Hospital
City
Östersund
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35841908
Citation
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.
Results Reference
derived

Learn more about this trial

RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.

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