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

Phase 3

Active, not recruiting

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
6-month dosing interval	Rituximab	This arm is receiving standard dose rituximab 500 mg every 6 months
12-month dosing interval	Rituximab	This arm is receiving the comparator dose rituximab 500 mg every 12 months

Primary Outcome Measures

Name	Time	Method
No evidence of disease activity (NEDA)	3 years	The proportion of patients maintaining No Evidence of Disease Activity-3 (NEDA-3) during year 2 - 4 of the trial: No relapse, no new T2 lesions (\> 3 mm), no EDSS progression in either dose arm

Secondary Outcome Measures

Name	Time	Method
Development of confirmed sustained disability	3 years	Proportion of patient with confirmed progression in EDSS according to pre-specified criteria
Time to first relapse	3 yeas	Time to first relapse for the two dose arms
Freedom of new or enlarged lesions on MRI	3 years	Proportion of patients in each dosing arm without new/enlarging T2 lesions
No evidence of disease activity (NEDA) in subgroups	4 years	The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial
Development of brain atrophy	3 years	Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume
Mean progression of disability	3 years	The mean change in EDSS over the trial period in the two dosing arms
Neurodegeneration	3 years	The mean change of s-NFL concentration between the two dosing arms
Dose persistence	3 years	Time to discontinuation of dosing regimen allocation
Development of hypogammaglobulinaemia	3 years	The occurrence of hypogammaglobulinaemia in the two dosing arms
Development of neutropenia	3 years	The occurrence of neutropenia in the two dosing arms
Development of infections	3 years	The occurrence of infections in the two dosing arms

Locations (17): Falun Hospital
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Falun, Sweden
Gävle Hospital
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Gävle, Sweden
Saghlgrenska Hospital
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Göteborg, Sweden
Helsingborg Hospital
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Helsingborg, Sweden
Linköping University Hospital
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Linköping, Sweden
South Älvsborg Hospital
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Borås, Sweden
Halland Hospital Kungsbacka
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Kungsbacka, Sweden
Nyköping Hospital
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Nyköping, Sweden
Anders Svenningsson
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Danderyd, Stockholm, Sweden
Karlstad Hospital
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Karlstad, Sweden
Karolinska Hospital Huddinge
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Stockholm, Sweden
Umeå University
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Umeå, Sweden
Capio StGöran Hospital
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Stockholm, Sweden
Fredrik Piehl
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Stockholm, Sweden
Uppsala Academiska Hospital
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Uppsala, Sweden
Örebro University Hospital
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Örebro, Sweden
Östersund Hospital
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Östersund, Sweden