A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
- Conditions
- Multiple Sclerosis, Primary Progressive
- Interventions
- Other: Placebo
- Registration Number
- NCT01194570
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 735
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. Placebo Ocrelizumab 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. Ocrelizumab 600 mg Ocrelizumab 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.
- Primary Outcome Measures
Name Time Method Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period 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 Outcome Measures
Name Time Method 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 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.
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 The SF-36v2 is a 36-item, self- reported, generic measure of quality of life that has been widely used in multiple disease areas. It is composed of 8 health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The PCS score was derived based on the SF-36 V2 User's Manual. Scoring for PCS involves (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming scale raw score to a 0-100 score. The PCS score was computed by (a) multiplying each health domain z score by a scale-specific physical factor score coefficient, (b) summing the resulting products, (c) converting the product total to T score. The total score ranges from 0-100, higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Number of Participants With at Least One Adverse Event (AE) From baseline to 9 years AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.
Trial Locations
- Locations (184)
Phoenix Neurological Associates Ltd
🇺🇸Phoenix, Arizona, United States
Barrow Neurology Clinic
🇺🇸Phoenix, Arizona, United States
Mayo Clinic- Scottsdale
🇺🇸Scottsdale, Arizona, United States
Arizona Neuroscience Research LLC
🇺🇸Phoenix, Arkansas, United States
Sutter East Bay Medical Foundation
🇺🇸Berkeley, California, United States
MS Center of Southern California
🇺🇸Newport Beach, California, United States
Univ of CA Davis Med Ctr; Neurology
🇺🇸Sacramento, California, United States
Univ of CA San Francisco; Department of Neurology
🇺🇸San Francisco, California, United States
University of Colorado; Anschutz Medical Campus Department of Neurology
🇺🇸Aurora, Colorado, United States
University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
🇺🇸Miami, Florida, United States
Scroll for more (174 remaining)Phoenix Neurological Associates Ltd🇺🇸Phoenix, Arizona, United States