This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.
Participants will be treated for a minimum of 120 weeks in the double-blind treatment (DBT) phase. Upon positive primary results after the DBT phase, an optional higher dose extension treatment, open-label extension (OLE) phase is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the lower limit of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the LLN.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
769
The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight \<75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)
Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg, IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.
Time to Onset of Composite Confirmed Disability Progression (cCDP) Sustained for at least 12 Weeks
Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by Expanded Disability Status Scale (EDSS), Timed 25-foot Walk Test (T25FWT) or 9-hole Peg Test (9-HPT)
Time frame: Baseline up to approximately 4.3 years
Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) Independent of Protocol-defined Relapses (PDR)
Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of PDR
Time frame: Baseline up to approximately 4.3 years
Time to Onset of 12-week Confirmed Disability Progression (CDP12)
CDP, defined as a sustained increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a sustained increase of ≥0.5 points in participants with a baseline EDSS score of \>5.5
Time frame: Baseline up to approximately 4.3 years
Time to ≥ 20% Increase in 12-week Confirmed by T25FWT
The T25FWT is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant is directed to start at one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible.
Time frame: Baseline up to approximately 4.3 years
Change in Neurofilament Light (NfL) at Week 96
Biomarker for neurodegeneration NfL
Time frame: Baseline up to Week 96
Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS12)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.
Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.
Alabama Neurology Associates
Homewood, Alabama, United States
21st Century Neurology
Phoenix, Arizona, United States
University of California Irvine
Irvine, California, United States
Stanford University Medical Center
Stanford, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Advanced Neurosciences Research LLC
Fort Collins, Colorado, United States
MS and Neuromuscular Center of Excellence
Clearwater, Florida, United States
University of South Florida
Tampa, Florida, United States
Baptist Health Lexington
Nicholasville, Kentucky, United States
International Neurorehabilitation Institute
Lutherville, Maryland, United States
...and 139 more locations
Self-reported measure of the impact of multiple sclerosis (MS) on the individual's ability to walk
Time frame: Baseline up to approximately 4.3 years
Annual Rate of Percent Change From Baseline in Total Brain Volume
Time frame: Baseline up to approximately 4.3 years
Annual Rate of Percent Change From Baseline in Thalamic Volume
Time frame: Baseline up to approximately 4.3 years
Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)
The SDMT is a performance measure that has demonstrated sensitivity in detecting not only the presence of cognitive impairment but also changes in cognitive functioning over time and in response to treatment. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected orally. A four-point change from baseline is typically considered clinically meaningful.
Time frame: Baseline up to approximately 4.3 years
Change in NfL (i.e. Ratio to Baseline) at Week 96 for Participants in the Approved Dose Ocrelizumab Group
Biomarker for neurodegeneration NfL
Time frame: Baseline up to Week 96
Change in NfL (i.e. Ratio to Baseline) at Week 96 for Participants in the Higher Dose Ocrelizumab Group
Biomarker for neurodegeneration NfL
Time frame: Baseline up to Week 96
Time to Onset of 24-week Composite Confirmed Disability Progression (cCDP24) Independent of PDR
Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of PDR
Time frame: Baseline up to approximately 4.3 years
Percentage of Participants With Adverse Events (AEs)
Time frame: Baseline up to approximately 8 years
Serum Concentrations of Ocrelizumab at Specified Timepoints
Time frame: Weeks 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Change in B-cell Levels in Blood
Time frame: Baseline up to approximately 4.3 years
Percentage of Participants Achieving 5 or Less B-cells per Microliter of Blood
Time frame: Baseline up to approximately 4.3 years
Change From Baseline in the Anti-drug Antibody (ADA) Levels
Time frame: Week 0, 24, 48, 72, 96, 120