Clinical trial NCT03979456: RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS
Official title: RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS. A Randomized Trial of Long-term Dosage of Rituximab in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Multiple sclerosis
Relapsing-Remitting
Dosing protocols
Randomized trial
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: No evidence of disease activity (NEDA)
timeFrame: 3 years
Secondary outcomes:
measure: No evidence of disease activity (NEDA) in subgroups
timeFrame: 4 years
measure: Time to first relapse
timeFrame: 3 yeas
measure: Freedom of new or enlarged lesions on MRI
timeFrame: 3 years
measure: Development of brain atrophy
timeFrame: 3 years
measure: Development of confirmed sustained disability
timeFrame: 3 years
measure: Mean progression of disability
timeFrame: 3 years
measure: Neurodegeneration
timeFrame: 3 years
measure: Dose persistence
timeFrame: 3 years
measure: Development of hypogammaglobulinaemia
timeFrame: 3 years
measure: Development of neutropenia
timeFrame: 3 years
measure: Development of infections
timeFrame: 3 years
Other outcomes:
measure: Health economy
timeFrame: 3 years
measure: Treatment Satisfaction Questionnaire
timeFrame: 3 years
Locations:
city: Danderyd
country: Sweden
facility: Anders Svenningsson
state: Stockholm
city: Borås
country: Sweden
facility: South Älvsborg Hospital
city: Falun
country: Sweden
facility: Falun Hospital
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Göteborg
country: Sweden
facility: Saghlgrenska Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Karlstad
country: Sweden
facility: Karlstad Hospital
city: Kungsbacka
country: Sweden
facility: Halland Hospital Kungsbacka
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Nyköping
country: Sweden
facility: Nyköping Hospital
city: Stockholm
country: Sweden
facility: Capio StGöran Hospital
city: Stockholm
country: Sweden
facility: Fredrik Piehl
city: Stockholm
country: Sweden
facility: Karolinska Hospital Huddinge
city: Umeå
country: Sweden
facility: Umeå University
city: Uppsala
country: Sweden
facility: Uppsala Academiska Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Östersund
country: Sweden
facility: Östersund Hospital
Study officials:
affiliation: Dept of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm
name: Anders Svenningsson, Professor
role: PRINCIPAL_INVESTIGATOR
References: