Remitting Relapsing Multiple Sclerosis MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Ocrevus
Product Name: Ocrelizumab
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Rituximab
Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution fo
Sponsors
Helse Bergen HF, Haukeland University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male and female patients, treatment naïve, and aged between 18 and 60 years included 2.Women of childbearing potential1 (WOCBP) able and willing to use highly effective methods of birth control2 per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly for the duration of the study OR until 3 months after last dose administered. 3.A diagnosis of RRMS according to the 2017 revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) within the last 12 months. 4.Disease activity defined as = 1 relapse3 or = 1 new MRI lesion4 during the last 12 months 5.EDSS score = 4.0 6.Absence of comorbidity or drug abuse that preclude study participation 7.Able to complete treatment or follow-up visits in the study (e.g. no contraindications for MRI or plans of moving) 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 211 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Known hypersensitivity or other known side effects for any of the study medications, including co-medications such as high glucocorticosteroids 2.A diagnosis of primary progressive MS according to the revised diagnostic criteria of McDonald (Thompson, Banwell et al. 2018) 3.A disease course of secondary progressive MS (Lublin, Reingold et al. 2014) 4.EDSS score > 4.0 5.Any ongoing infection, including tuberculosis, VZV, hepatitis virus or HIV, as well as hepatitis B surface antigen positivity and/or hepatitis C PCR positivity verified at screening visit. 6.Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol. 7.Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV) 8.Active malignancy or prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. 9.WBC 1,5 x 109/L before start of study treatment. 10.Platelet (thrombocyte) count 200 µmol/L 13.Serum bilirubin > ULN 14.Pregnancy or lactating female patients 15.Any disease that can influence the patient safety and compliance, or the evaluation of disability 16.History of life-threatening infusion reaction to ocrelizumab or rituximab, if previously treated with these medications for other diseases than MS 17.Treatment with glucocorticoids or ACTH within one month prior to start of study treatment 18.Previous use of MS-therapies such as natalizumab, fingolimod, interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, cladribine, rituximab, alemtuzumab, ocrelizumab, hematopoietic stem cell therapy (HSCT) or other immunosuppression therapies with long lasting effects, or any other disease modifying therapy (DMT) for MS. 19.Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study (s), or receiving other investigational treatment(s). Patients participating in a purely observational trial will not be excluded. 20.Presence of metallic objects implanted in the body, or allergy to MRI contrast that would preclude the ability of the patient to safely have MRI exams 21.Current alcohol or drug dependencies
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Proportion of patients with 6-months confirmed disability progression (6M-CDP) as measured by the Expanded disability status scale (EDSS) from baseline to month 24. CDP-EDSS defined as an increase of one point in the EDSS score confirmed after 6 months, with an absence of relapse at the time of assessment. •Proportion of patients with 6-months confirmed disability improvement (6M-CDI) as measured by the Expanded disability status scale (EDSS) from baseline to month 24. CDI-EDSS is defined as a decrease of one point in the EDSS score, confirmed after 6 months, with an absence of relapse at the time of assessment. •The annual relapse rate from baseline to month 24 •Proportion of patients without relapses from baseline to month 24 •Proportion of patients with 6M-CDP in T25FW from baseline to month 24. 6M-CDP in T25FW is defined as patients experiencing an increase of =20% from baseline which is confirmed after 6 months •Proportion of patients with 6M-CDP in 9-HPT from baseline to month 24. 6M-CDP in 9HPT is defined as patients experiencing an increase of =20% from baseline which is confirmed after 6 months •Proportion of patients with 6M-CDP in SDMT from baseline to month 24. 6-month CDP in SDMT is defined as patients experiencing a reduction of 15% from baseline which is confirmed after 6 months •Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from baseline to month 6, and from baseline to month 24 •Proportion of patients without new gadolinium enhancing T1-weighted brain MRI lesions at month 6, month 12 and month 24 •Change in brain volumes from baseline to month 24 and from month 6 to month 24 •Overall safety during 24 months of treatment •The frequency of immediate and delayed infusion reactions during 24 months of treatment •The frequency of infections during 24 months of treatment •The frequency any malignancies during 24 months of treatment •Change in the quality of life as measured by MS i | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate non-inferiority of rituximab compared to ocrelizumab with regards to efficacy and safety in treatment of naïve RRMS patients, diagnosed within the last 12 months. ;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint is to determine the difference in efficacy and safety between rituximab and ocrelizumab according to the following criteria: •Proportion of patients with no new or enlarging T2-weighted brain MRI lesions from month 6 (re-baseline) to month 24 ;Timepoint(s) of evaluation of this end point: From re-baseline at 6 months to 24 months. | — |
Countries
Norway, Sweden
Contacts
Public ContactØivind Fredvik Grytten Torkildsen
Helse Bergen HF, Haukeland University Hospital
Outcome results
None listed