RItuximab Versus FUmarate in Newly Diagnosed Multiple Sclerosis.

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02746744
• Other study ID #: EudraCT 2015-004116-38
• Status: Completed
• Phase: Phase 3
• Start date: May 2016
• Est. completion date: August 2021

Study information

• Verified date: October 2021
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: August 2021
• Est. primary completion date: July 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Rituximab
Infusion of Mabthera/Rituximab every 6 months
• Dimethyl fumarate
Intake of Tecfidera/Dimethyl Fumarate daily acc. to clinical practice.
• Sodium Chloride solution
Placebo/Sham infusion every 6 months so that the examining physician (blinded) should not know which patient gets Mabthera or Tecfidera

Locations

Country	Name	City	State
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	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

Sponsors (1)

Lead Sponsor	Collaborator
Anders Svenningsson

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom of relapse	The relative risk of experiencing a relapse during the two-year period for either compound.	Within 2 years