A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis
ID: NCT01194570
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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.
Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.
Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.
Treatment Arms Description
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.
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.
- 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
Primary Outcome Measures
- 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.
View Secondary Outcome Measures (6)
- Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 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.
- Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120 — Time Frame: Baseline, Week 120
- Percent Change From Baseline in Total Volume of T2 Lesions at Week 120 — Time Frame: From Baseline to Week 120
- Percent Change in Total Brain Volume From Week 24 to Week 120 — Time Frame: From Week 24 to Week 120
- Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120 — Time Frame: 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) — Time Frame: From baseline to 9 years
AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.
This trial is recruiting at 184 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 184 Facilities & Contact Sites
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- Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.PubMed ↗
- Zivadinov R, Pei J, Clayton D, Goldman DE, Winger RC, Cabatingan MS, Dwyer MG, Bergsland N. Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study. J Neurol Neurosurg Psychiatry. 2024 May 14;95(6):536-543. doi: 10.1136/jnnp-2023-332573.PubMed ↗
- Loomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0.PubMed ↗
- Hauser SL, Bar-Or A, Weber MS, Kletzl H, Gunther A, Manfrini M, Model F, Mercier F, Petry C, Wing Q, Koendgen H, Smith T, Kappos L. Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 15;10(2):e200094. doi: 10.1212/NXI.0000000000200094. Print 2023 Mar.PubMed ↗
- Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.PubMed ↗
View Official Medical/Scientific Title
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