Patients with multiple sclerosis (MS), 20 - 52 years of age, that have completed the RIFUND-MS trial (EudraCT 2015-004116-38) will be offered to continue in this extension trial, RODOSE-MS. In addition, patients will be recruited that has not participated in the RIFUND trial but has been treated with rituximab with the same protocol as in the RIFUND trial as part of clinical practice.
Conditions
Interventions
Trade Name: Mabthera
Product Name: Mabthera
Pharmaceutical Form: Infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital
Eligibility
Sex/Gender
All
Inclusion 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 • 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 a total of 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. * Occasional extended dose interval for up to 12 months in conjunction with the COVID epidemic is allowed 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
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 • 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, eg delayed menstrual period more than five days above expected time. • Patients having contraindication for or otherwise not compliant with MRI investi-gations • 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 rele-vant 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, eg 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 any of the IP:s • Severe psychiatric condition ** Up to 6 months initial treatment with natalizumab in conjunction with the COVID epidemic or for completing vaccination before inclusion in the trial is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is • To assess long-term efficacy and safety of rituximab in RRMS while comparing two different dosing regimens. ;Secondary Objective: The secondary objectives of the study are • To compare effects on brain atrophy measures via magnetic resonance imaging between treatment with two long-term dosing regimens of Rituximab in MS. • To compare effects on cerebrospinal fluid markers between axonal damage from treatment with two long-term dosing regimens of Rituximab in MS. • To compare effects on serum markers for axonal damage between treatment with two long-term dosing regimens of Rituximab in MS. • To compare the rate of disability progression between treatment with two long-term dosing regimens of Rituximab in MS. • To compare the occurrence of immunological side-effects such as hypogammag-lobulinaemia and late onset neutropenia between treatment with two long-term dosing regimens of Rituximab in MS. • To compare the occurrence of severe infections between treatment with two long-term dosing regimens of Rituximab in MS. ;Primary end point(s): The primary endpoint of this study is • 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. ;Timepoint(s) of evaluation of this end point: When all included subjects have been followed for the full duration of 4 years in the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are • The proportion of patients maintaining NEDA-3 comparing the previous rituximab arm with the previous DMF arm from the RIFUND trial • Time to first relapse for the two dosing regimens • Treatment effect evaluated by MRI o Proportion without new/enlarging T2 lesions o Evolution of brain atrophy measured as brain parenchymal fraction (BPF) and corpus callosum area or -volume • Treatment effect as confirmed worsening evaluated via EDSS o Proportion of patient with confirmed progression in EDSS according to pre-specified criteria o The mean change in EDSS over the trial period • Treatment effect evaluated via levels of Neurofilament-Light protein in serum o Serum will be stored from blood samples each six month during the study, in total nine occasions • Treatment effect evaluated via levels of Neurofilament-Light protein in the CSF o The patients will be asked to participate in this part as an optional study involving LP at three occasions. • Time to discontinuation of dosing regimen allocation, ie “dose survival” analysis. • The occurrence of hypogammaglobulinaemia in the two dose arms • The occurrence of neutropenia in the two dose arms • The occurrence of infections in the two dose arms ;Timepoint(s) of evaluation of this end point: When all included subjects have been followed for the full duration of 4 years in the trial | — |
Countries
Sweden
Contacts
Public ContactDepartment of Clinical Sciences, KI
Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital
Outcome results
None listed