A clincial study comparing the effectiveness of two drugs, named Rituximab and Dimethyl Fumarate (Tecfidera®), for the neurological disease Multiple Sclerosis.

RItuximab versus FUmarate in Newly Diagnosed Multiple Sclerosis – RIFUND-MS A randomized phase 3 study comparing Rituximab with Dimethyl Fumarate in early Relapsing-Remitting Multiple Sclerosis Objective: To compare the efficacy of rituximab on the ability to prevent relapses in early RRMS and CIS compared with dimethyl fumarate (DMF), which is an approved first-line medication for RRMS today, using a phase 3 design. Population: Patients with newly diagnosed RRMS or CIS with no more than 10 years disease duration (since diagnosis), 18 – 50 years of age and previously not treated with immunomodulating drugs OR treated with first-line injectables. Patients should display protocol-defined clinical or radiological disease activity during the preceding year before screening for inclusion. Intervention: Treatment with rituximab (Mabthera®) with an initial dose of 1000 mg intravenously (iv) followed by 500 mg iv every six months. Control: Treatment with DMF (Tecfidera®) 240 mg twice daily. The two treatments are randomised in a 1:1 proportion. Outcome: Primary outcome is the relative risk of experiencing a relapse during the two–year period for either compound. As secondary endpoints worsening on neurological disability, magnetic-resonance imaging-defined disease activity and effect on cerebrospinal fluid biomarkers will be analysed. In addition, health-economic evaluations of using rituximab as first-line treatment for RRMS will be performed.

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-004116-38-SE

Enrollment

200

Registered

2015-10-20

Start date

2015-12-18

Completion date

Unknown

Last updated

2023-10-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Patients with multiple sclerosis (MS) or patients presenting with symptoms highly suspicious of MS while not completely fulfilling diagnostic criteria, 18 - 50 years of age and no more than 10 years of disease duration (from diagnosis). Patients treated with immunomodulatory drugs or treated with first-line injectable therapies (eg interferons or glatiramer acetate) may be included.

Interventions

Trade Name: Mabthera Pharmaceutical Form: Infusion INN or Proposed INN: RITUXIMAB CAS Number: 174722-31-7 Concentration unit: mg milligram(s) Concentration type: range Concentration number: 500-1000 P

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: A subject will be eligible for inclusion in this study if all of the following criteria apply: • Diagnosis of Relapsing Remitting MS according to the 2017 revised McDonald criteria OR one demyelinating episode in conjunction with at least one asymptomatic 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 10 years of disease duration (since MS diagnosis) • During the previous year, clinical or radiological disease activity defined as at least one of the following: o = 1 relapse o = 2 T2 lesions o = 1 Gd+ lesions • EDSS 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria ap-plies: • Diagnosis of Progressive MS • Pregnant or lactating women • Patients having contraindication for or otherwise not compliant with MRI investigations • Simultaneous treatment with other immunosuppressive drugs • Documented allergy or intolerance to any of the IP:s • Severe psychiatric condition

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of this study is •To compare clinical efficacy between rituximab administered according to a Swed-ish treatment schedule and dimethyl fumarate administered according to label ;Secondary Objective: The secondary objectives of the study are •To compare effects on magnetic resonance imaging from treatment with rituximab and dimethyl fumarate •To compare effects on cerebrospinal fluid markers for axonal damage from treat-ment with rituximab and dimethyl fumarate •To compare effects on serum levels of the axonal injury marker neurofilament light from treatment with rituximab and dimethyl fumarate •To compare the rate of disability progression during the trial •To make health economic assessments, including work capacity, and compare cost – effectiveness between Rituximab and dimethyl fumarate •To compare patient satisfaction and health related quality of life during long-term treatment of RRMS patients with Rituximab and dimethyl fumarate ;Primary end point(s): The primary endpoints of this study is •The relative risk of experiencing a relapse during the two–year period for either compound. ;Timepoint(s) of evaluation of this end point: While all subjects in the trial has received treatment with either of the IMP for two years	—

Measure

Time frame

Main Objective: The primary objective of this study is •To compare clinical efficacy between rituximab administered according to a Swed-ish treatment schedule and dimethyl fumarate administered according to label ;Secondary Objective: The secondary objectives of the study are •To compare effects on magnetic resonance imaging from treatment with rituximab and dimethyl fumarate •To compare effects on cerebrospinal fluid markers for axonal damage from treat-ment with rituximab and dimethyl fumarate •To compare effects on serum levels of the axonal injury marker neurofilament light from treatment with rituximab and dimethyl fumarate •To compare the rate of disability progression during the trial •To make health economic assessments, including work capacity, and compare cost – effectiveness between Rituximab and dimethyl fumarate •To compare patient satisfaction and health related quality of life during long-term treatment of RRMS patients with Rituximab and dimethyl fumarate ;Primary end point(s): The primary endpoints of this study is •The relative risk of experiencing a relapse during the two–year period for either compound. ;Timepoint(s) of evaluation of this end point: While all subjects in the trial has received treatment with either of the IMP for two years

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Secondary

Measure	Time frame
Secondary end point(s): The secondary endpoints are • Treatment effect evaluated via MRI - Numbers of Gd+ lesions and new/enlarging T2 lesions - Evolution of brain atrophy measured as brain parenchymal fraction (BPF) • Treatment effect evaluated via levels of Neurofilament-Light protein in the CSF - The patients will be asked to participate in this part as an optional study involving LP at four occasions. • Treatment effect evaluated via levels of Neurofilament-Light protein in the serum • Treatment effect as confirmed worsening evaluated via EDSS - Proportion of patient with confirmed progression in EDSS according to pre-specified criteria - The mean change in EDSS over the trial period • Proportion of patients with No Evidene of Disease Activity (NEDA) -3 (free of ex-acerbations, new/enlarged T2-lesions and occurrence of Gd+ lesions) as well as NEDA-4 (NEDA-3 plus no worsening of EDSS from baseline) • Proportion rescue treatments from insufficient treatment effect determined by MRI in the two treatment arms;Timepoint(s) of evaluation of this end point: While all subjects in the trial has received treatment with either of the IMP for two years	—

Measure

Time frame

Secondary end point(s): The secondary endpoints are • Treatment effect evaluated via MRI - Numbers of Gd+ lesions and new/enlarging T2 lesions - Evolution of brain atrophy measured as brain parenchymal fraction (BPF) • Treatment effect evaluated via levels of Neurofilament-Light protein in the CSF - The patients will be asked to participate in this part as an optional study involving LP at four occasions. • Treatment effect evaluated via levels of Neurofilament-Light protein in the serum • Treatment effect as confirmed worsening evaluated via EDSS - Proportion of patient with confirmed progression in EDSS according to pre-specified criteria - The mean change in EDSS over the trial period • Proportion of patients with No Evidene of Disease Activity (NEDA) -3 (free of ex-acerbations, new/enlarged T2-lesions and occurrence of Gd+ lesions) as well as NEDA-4 (NEDA-3 plus no worsening of EDSS from baseline) • Proportion rescue treatments from insufficient treatment effect determined by MRI in the two treatment arms;Timepoint(s) of evaluation of this end point: While all subjects in the trial has received treatment with either of the IMP for two years

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Countries

Sweden

Contacts

Public ContactDepartment of Clinical Sciences, KI

Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet

anders.svenningsson@ki.se468123 555 33

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026