Multiple sclerosis. MedDRA version: 21.1 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system di
Conditions
Interventions
Trade Name: Ocrevus
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
CAS Number: 637334-45-3
Other descriptive name: OCRELIZUMAB
Concentration unit: mg/ml mi
Sponsors
Danish Multiple Sclerosis Center, Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =18 and =65 years • MS diagnosis and definition of disease course according to the 2017 McDonald criteria • Expanded disability status scale (EDSS) =6.5 • Fulfilling criteria for active MS: o Treatment naïve RRMS patients (never treated, or no DMT the previous 3 months): ? =2 relapse previous 12 months OR ? =1 relapse previous 12 months AND =9 T2 lesions on brain and/or spinal MRI AND =1 contrast-enhancing lesion or =1 new or enlarging T2 lesion on brain and/or spinal MRI previous 12 month o Previously treated RRMS patients: ? =1 relapse previous 12 months OR ? =1 contrast-enhancing lesion or =2 new/enlarging T2 lesions on brain MRI previous 12 months o Progressive MS patients: ? =1 relapse previous 12 months OR ? =1 contrast-enhancing lesion previous 12 months or =1 new/enlarging T2 lesions on brain MRI previous 12 months or =2 new or enlarging T2 lesion on brain MRI previous 24 months OR ? Increased levels of neurofilament light chain in serum or cerebrospinal on sample collected previous 12 months Progressive MS patients not fulfilling the clinical/MRI criteria for active disease, may qualify for inclusion in the study if: ? CSF NFL level (measured with NF-Light® ELISA assay from Uman Diagnostics or Simoa): o 18 to 40 years >560 ng/l o 41 to 60 years >890 ng/l o 61 to 65 years >1850 ng/l ? sNFL level (measured with Simoa™ NF-light® Advantage Kit) o 18 to 20 years >7.4 ng/l o 21 to 30 years >9.9 ng/l o 31 to 40 years >13.1 ng/l o 41 to 50 years >17.5 ng/l o 51 to 60 years >23.3 ng/l o 61 to 75 years >30.9 ng/l • Signed written informed consent long-term follow-up phase of the study: Standard dosing: • Completed the first 24 months of the study • No signs of active disease the previous 18 months Inclusion criteria for extended interval dosing sub-study though randomisation • Completed the first 24 months of the study • No signs of active disease the previous 18 months • Signed written informed consent Inclusion criteria for extended interval dosing outside the randomisation process • Completed the first 24 months of the study • Recommended by physician to switch to extended interval dosing due to Low IgG (=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Pregnancy or breast feeding • Lack of effective contraception for women of child-bearing potential Effective contraception includes: ? Oral contraception (combined and progestogen-only) ? Intrauterine devices and intrauterine hormone-releasing system ? Bilateral tubal occlusion ? Vasectomised partner (provided that partner is the sole sexual partner) ? Sexual abstinence (refraining from heterosexual intercourse during the study period; sexual abstinence should be evaluated in relation to the participants preferred and usual lifestyle) ? Other forms of contraception with failure rate <1% • Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization • Active malignant disease in the previous 5 years • Positive test for HIV, hepatitis B or C, or tuberculosis • Negative test for varicella zoster • Lymphopenia grade 2 (0.5 to 0.8 × 109/L) or higher grades of lymphopenia (in case of switching from fingolimod, siponimod or ozanimod lymphopenia is accepted at screening visit (note that treatment with interferon-beta can induce transient lymphopenia) • Neutropenia grade 2 (1.0 to 1.5 × 109/L) or higher grades • Thrombocytopenia grade 2 (50 to 75 × 109/L) or higher grades • Previous treatment with alemtuzumab or hematopoietic stem-cell transplantation • Previous treatment with cladribine, CD20-depleting antibodies, daclizumab or other immune suppressive treatment which is judged to still exert immune suppressive effect by treating physician • Methylprednisolone treatment 4 weeks within baseline visit and baseline MRI scan • Findings on the screening MRI (for patients without MRI scan of the brain the previous 12 months the baseline MRI scan is also used as screening MRI) judged to preclude participation by the treating physician • Other diseases judged to be relevant by the treating physician • Contraindication to MRI • Known allergy or hypersensitivity to rituximab or ocrelizumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary aims include evaluation of other standard efficacy and safety endpoints and tertiary, explorative endpoints related to assessment of efficacy and safety (blood flow cytometry, whole blood gene expression, genotyping of Fc?-receptor or complement genes, serum NFL, IgG concentrations) in the 24-month core study period. ;Primary end point(s): •Percentage of patients with no new or enlarging T2 white matter lesions ;Timepoint(s) of evaluation of this end point: From month 6 to month 24;Main Objective: The primary aim of the study is to test whether rituximab treatment is non-inferior to ocrelizumab treatment in active forms of multiple sclerosis, which will be evaluated with the primary endpoint percentage of patients with no new or enlarging T2 white matter lesions from month 6 to month 24. Patients completing the core-study of 24 months treatment, will be asked to continue in the extension study of additional 36 months duration. The extension long-term phase of the study (month 24 to month 60) will evaluate the long term efficacy and safety of rituximab and ocrelizumab therapy given as either standard dosing or extended interval dosing. The long-term phase of the study will examine whether extended interval dosing may be a preferable dosing strategy for patients who have been stable on well-established CD20-depleting therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Percentage of patients with 6-month confirmed disease worsening (CDW) in EDSS from baseline to month 24 • ARR based on cumulative number of confirmed relapses from baseline to months 24 • Percentage of patients with 6-months CDW in T25FW from baseline to month 24 • Percentage of patients with 6-months CDW in 9HPT from baseline to month 24 • Percentage of patients with 6-months CDW in SDMT from baseline to month 24 • Change in MSIS-29 from baseline to month 24 • Change in FSMC from baseline to month 24 • EQ-5D (5-level version) from baseline to month 24 • Percentage of patients without GdEL on month 6 and month 24 scans • Change in T2 white matter lesion volume from month 6 to month 24 • Change in T1 white matter lesion volume from month 6 to month 24 • PBVC from month 6 to month 24 • Difference in serum NFL level from baseline to month 24 • Blood levels of CD19+ B cells at month 6 and month 24 ;Timepoint(s) of evaluation of this end point: See definition above for each endpoint. | — |
Countries
Denmark
Contacts
Public ContactDanish Multiple Sclerosis Center
Danish Multiple Sclerosis Center, Rigshospitalet
Outcome results
None listed