A Phase III, Multicentre, Randomized, Parallel-group, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 735
- Locations
- 184
- Primary Endpoint
- Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period
Study Overview
Brief Summary
This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of primary progressive multiple sclerosis (according to revised McDonald criteria)
- •EDSS at screening from 3 to 6.5 points
- •Disease duration from onset of MS symptoms less than (<) 15 years if EDSS greater than (>) 5.0; <10 years if EDSS greater than or equal to (>/=) 5.0
- •Sexually active male and female participants of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose
Exclusion Criteria
- •History of relapsing remitting MS, secondary progressive, or progressive relapsing MS at screening
- •Inability to complete an MRI (contraindications for MRI)
- •Known presence of other neurologic disorders
- •Known active infection or history of or presence of recurrent or chronic infection
- •History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
- •Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
- •Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-cluster of differentiation 4 (CD4), cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
- •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
Arms & Interventions
Placebo
Participants with primary progressive multiple sclerosis (PPMS) received placebo matched to ocrelizumab at a schedule interval of 24 weeks up to at least 120 weeks.
Intervention: Ocrelizumab (Drug)
Placebo
Participants with primary progressive multiple sclerosis (PPMS) received placebo matched to ocrelizumab at a schedule interval of 24 weeks up to at least 120 weeks.
Intervention: Placebo (Other)
Ocrelizumab 600 mg
Participants with PPMS received ocrelizumab as two IV infusions of 300 mg separated by 14 days at a scheduled interval of every 24 weeks up to at least 120 weeks.
Intervention: Ocrelizumab (Drug)
Outcomes
Primary Outcomes
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period
Time Frame: Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit \>=12 weeks (\>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of \>= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is \<=5.5 points (inclusive), or an increase of \>=0.5 points, if baseline EDSS is \>5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.
Secondary Outcomes
- Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period(Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm)
- Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120(Baseline, Week 120)
- Percent Change From Baseline in Total Volume of T2 Lesions at Week 120(From Baseline to Week 120)
- Percent Change in Total Brain Volume From Week 24 to Week 120(From Week 24 to Week 120)
- Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120(From Baseline to Week 120)
- Number of Participants With at Least One Adverse Event (AE)(From baseline to 9 years)