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

• Register: EUCTR
• Last refreshed on: 9 October 2023
• Main ID: EUCTR2015-004116-38-SE
• Date of registration: 20/10/2015
• Prospective Registration: Yes
• Primary sponsor: Department of Clinical Sciences, Danderyd Hospital
• Public title: A clincial study comparing the effectiveness of two drugs, named Rituximab and Dimethyl Fumarate (Tecfidera®), for the neurological disease Multiple Sclerosis.
• Scientific title: 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.
• Date of first enrolment: 18/12/2015
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004116-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Sweden

Contacts

• Name: Department of Clinical Sciences, KI
• Affiliation: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet

• Name: Department of Clinical Sciences, KI
• Affiliation: Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet

Key inclusion & exclusion 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:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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.

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

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
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

Trade Name: Tecfidera
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 480-

Primary Outcome(s)

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

Secondary Outcome(s)

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

Secondary ID(s)

RIFUND-MS

Source(s) of Monetary Support

Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet

Ethics review

Status: Approved
Approval date: 04/12/2015
Contact: