Relapsing remitting multiple sclerosis (RRMS) MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Ocrelizumab
Product Code: RO4964913/F07
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO496491
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-55 years - Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria - Have a length of disease duration, from first symptom, of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Secondary progressive multiple sclerosis (SPMS) or history of primary progressive or progressive relapsing MS - Inability to complete an MRI - Known presence of other neurological disorders Exclusions Related to General Health - Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study - History or currently active primary or secondary immunodeficiency - History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies - History of opportunistic infections - History or known presence of recurrent or chronic infection - History of malignancy - Congestive heart failure - Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds Exclusions Related to Medications - Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit - Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS - Treatment with fampridine/dalfamipridine (Fampyra®)/Ampyra®) unless on stable dose for >= 30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the 96-week treatment period. - Contraindications to or intolerance of oral or IV corticosteroids, according to the country label, including a) Psychosis not yet controlled by a treatment; b) Hypersensitivity to any of the constituents - Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab) - Systemic corticosteroid therapy within 4 weeks prior to screening - Any previous treatment with alemtuzumab (Campath/Mabcampath/Lemtrada), cladribine, mitoxantrone, daclizumab, laquinimod, total body irradiation, or bone marrow transplantation - Treatment with cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine or methotrexate - Treatment with fampridine/dalfamipridine (Fampyra®)/Ampyra®) unless on stable dose for >= 30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the 96-week treatment period. - Previous treatment with natalizumab unless natalizumab was discontinued because of persistent anti-natalizumab antibodies - Treatment with IV immunoglobulin (Ig) within 12 weeks prior to baseline - Any previous treatment with an investigational MS DMT not yet approved at time of screening Exclusions Related to Laboratory Findings - Positive serum ß human chorionic gonadotropin (hCG) measured at screening - Positive screening tests for hepatitis B (hepatitis B surface antigen [HBsAg] positive, or positive hepatitis B core antibody [total HBcAb] confirmed by a positive viral DNA polymerase chain reaction [PCR]) or hepatitis C (HepCAb) - Lymphocyte count below lower limit of normal (LLN) - CD4 count 3.0 × the upper limit of normal (ULN) - Platelet count <100,000/µL (<100 × 109/L) - Absolute neutrophil count <1.0 × 103/mcL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of ocrelizumab 600 mg intravenous (IV) given every 24 weeks on the basis of the following endpoint - Proportion of patients who have no evidence of disease activity ;Primary end point(s): 1. Proportion of patients who have no evidence of disease activity (NEDA), as per protocol defined events over 96-weeks (with MRI baseline at Week 8);Timepoint(s) of evaluation of this end point: 1. Up to 96 weeks;Secondary Objective: •To evaluate the efficacy of ocrelizumab 600 mg IV given every 24 weeks on the basis of the following endpoints - Proportions of patients free from a protocol-defined event of disease activity - Time to first protocol-defined event of disease activity - Change in Expanded Disability Status Scale (EDSS) - Proportion of patients who have Confirmed Disability Improvement (CDI), Confirmed Disability Progression (CDP) or stable disability - Annualized rate of protocol-defined relapses - Time to onset of first protocol-defined relapse, 24 weeks CDP, first new and/or enlarging T2 lesion - Total number of T1 Gd-enhanced lesions detected by brain MRI - Total number of new/enlarging T2 lesions detected by brain MRI - Volume and number of new and/or enlarging T2 hyperintense lesions - Change in T1 hypointense lesions - Change in cognitive performance •To evaluate the safety and tolerability of ocrelizumab 600 mg IV given every 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportions of patients free from a protocol-defined event of disease activity during a 24-week period and a 48-week period 2. Time to first protocol-defined event of disease activity 3. Change in EDSS from Baseline to Week 96 4. Proportion of patients who, over a 96-week period, have CDI, CDP or stable disability 5. Annualized rate of protocol-defined relapses at Week 96 6. Time to onset of first protocol-defined relapse 7. Time to onset of 24 weeks CDP 8. Time to onset of first new and/or enlarging T2 lesion 9. Total number of T1 Gd-enhanced lesions detected by brain MRI at Weeks 24, 48 and 96 10. Change in total T2 lesion volume detected by brain MRI from Baseline to Weeks 96 11. Change in T1 hypointense volume from Baseline to Weeks 48 and 96 12. Change in brain volume from baseline measured at Weeks 24, 48 and 96 13. Volume and number of new and/or enlarging T2 hyperintense lesions from baseline to Weeks 24, 48 and 96 14. Change from Baseline in cognitive performance at Week 48 and Week 96 as measured by the BICAMS 15. Incidence of adverse events 16. Changes in vital signs, physical and neurological examinations, clinical laboratory results, locally reviewed MRI for safety and concomitant medications;Timepoint(s) of evaluation of this end point: 1. at Weeks 24 and 48 2. Up to 96 weeks 3. Baseline and Week 96 4. Up to 96 weeks 5. at Week 96 6-8. Up to 96 weeks 9. at Weeks 24, 48 and 96 10. Baseline and 96 11. Baseline, Weeks 48, and 96 12-13. Baseline, Weeks 24, 48, and 96 14. Baseline, Weeks 48, and 96 15-16. Up to Week 192 | — |
Countries
Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, Turkey, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed