This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS. The study will be conducted in two cohorts i.e. RMS cohort (4 arm group) and PPMS cohort (one arm group). RMS cohort: Ocrelizumab will be administered as two intravenous (IV) infusions of 300 milligrams (mg) on Days 1 and 15. Subsequent doses will be given as single 600-mg infusions at Weeks 24 and 48. Participants will be randomized in 1:1:1 ratio to receive lumbar puncture (LP) post-treatment at Week 12, 24, or 52 following the first dose of ocrelizumab in three arm groups. A fourth RMS arm with delayed treatment start (Arm 4 \[control group\]) will not be a part of the randomization and will be recruited separately, wherein treatment with ocrelizumab will be delayed for 12 weeks from pre-treatment baseline. PPMS cohort: Ocrelizumab 600 mg will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks. Participants will receive a LP at the start of the study before dosing with ocrelizumab and second LP at Week 52 following the first dose of ocrelizumab. A long-term extension will be conducted for participants that complete the study and continue to receive ocrelizumab. Treatment with ocrelizumab in the entire study will continue for approximately 4.5 years after the first infusion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
131
Ocrelizumab will be administered as IV infusion.
Participants will receive LP as specified in individual arms. Lumbar puncture is optional at week 52, except for RMS Cohort Arm 3 and PPMS Cohort. In addition, the lumbar punctures in the Long Term Extension phase is every other year.
Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.
Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.
Stanford University
Palo Alto, California, United States
University of California at San Francisco
San Francisco, California, United States
University Of Colorado
Aurora, Colorado, United States
Yale University School of Medicine ; Pulmonary & Critical Care
New Haven, Connecticut, United States
University of Massachusetts Medical School
Worcester, Massachusetts, United States
Washington University; Wash Uni. Sch. Of Med
St Louis, Missouri, United States
Empire Neurology, PC
Latham, New York, United States
Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr
New York, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Ohio State University
Columbus, Ohio, United States
...and 7 more locations
Change in Levels of NfL (Neurofilament Light) in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab
Primary Analysis was based on following data-cut off: Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
Change in Number of CD19+ B Cells in CSF From Treatment Baseline to Post-Treatment With Ocrelizumab
Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab
Arm 1: Baseline to post-treatment at 12 weeks Arm 2: Baseline to post-treatment at 24 weeks Arm 3: Baseline to post-treatment at 52 weeks Arm 4: Baseline to post-treatment at 12 weeks PPMS Cohort: Baseline to post-treatment at 52 weeks
Time frame: From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
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