RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS

NCT ID: NCT03979456

Last Updated: 2021-04-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-04
• Study Completion Date: 2025-06-01

Brief Summary

A randomized trial of long-term dosage of rituximab in multiple sclerosis

Detailed Description

This is a prospective randomized phase 3 study comparing two dosing regimens of Rituximab in long-term treatment of MS. Primary endpoint is no evidence of disease activity (NEDA) in a non-inferiority analysis between 12-months dosing interval of 500 mg rituximab with 6-months dosing interval. The endpoint is a compound of being free from release, new or enlarging MRI lesions and sustained progression of disability measured by EDSS.

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. MRI investigations will be performed blinded for the dosing arm allocation.

Randomization will be performed via a randomization module in the national Swedish MS registry. The patients will be randomized 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. This will lead to a high degree of validity in relation to expected outcome in clinical practice.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

6-month dosing interval

This arm is receiving standard dose rituximab 500 mg every 6 months

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

After one year in the trial, the patients are split in the two dosing-arms described above. The dose-comparison phase continues four years.

12-month dosing interval

This arm is receiving the comparator dose rituximab 500 mg every 12 months

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

After one year in the trial, the patients are split in the two dosing-arms described above. The dose-comparison phase continues four years.

Interventions

Rituximab

After one year in the trial, the patients are split in the two dosing-arms described above. The dose-comparison phase continues four years.

Intervention Type: DRUG

Other Intervention Names

Mabthera

Eligibility Criteria

Inclusion Criteria

• 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
• The patient has completed the RIFUND-MS trial and is treated with either of the study medications rituximab or DMF at the last visit of the RIFUND trial OR has been treated with rituximab with a dose regimen of 500 - 1000 mg followed by 500 mg every 6 months for up to two years as part of clinical practice
• Age 20 - 52 years (inclusive)
• EDSS 0 - 5,5 (inclusive)
• The patient is willing and able to give written informed consent, according to the judgement of the investigator.
• 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 FSH level in the postmenopausal range.

Exclusion Criteria

• Diagnosis of Progressive MS
• Previous treatment with any "second-line" immunomodulatory drug, eg natalizumab, alemtuzumab, fingolimod, or other long-acting immunosuppressive agents.
• Pregnant or lactating women s-HCG will be tested on all women at screening, before each study-related infu-sion and in any situation where there is a reason to suspect pregnancy during the trial, e.g 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 if not tested within the previous three years.
• Severe cardiac disorder, e.g 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 the IP
• Severe psychiatric condition

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 52 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Anders Svenningsson

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anders Svenningsson, Professor

Role: PRINCIPAL_INVESTIGATOR

Dept of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm

Locations

Anders Svenningsson

Danderyd, Stockholm County, Sweden

South Älvsborg Hospital

Borås, , Sweden

Falun Hospital

Falun, , Sweden

Gävle Hospital

Gävle, , Sweden

Saghlgrenska Hospital

Gothenburg, , 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

Fredrik Piehl

Stockholm, , Sweden

Karolinska Hospital Huddinge

Stockholm, , Sweden

Umeå University

Umeå, , Sweden

Uppsala Academiska Hospital

Uppsala, , Sweden

Countries

Sweden

Other Identifiers

EudraCT 2018-000721-31

Identifier Type: -

Identifier Source: org_study_id