RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS
RItuximab Long-Term DOSE Trial in Multiple Sclerosis - RIDOSE-MS
A randomized trial of long-term dosage of rituximab in multiple sclerosis
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.
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