Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS) (NCT NCT04548999)

Last Updated: 2026-07-24

Results Overview

Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of the 3 criteria: 1) CDP=12-week confirmed increase (CI) from baseline (FB) in expanded disability status scale (EDSS) score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of \>5.5 OR 2) 12-week CI of ≥20% FB in Timed 25-foot Walk Test (T25FWT) score OR 3)12-week CI of ≥ 20% FB in 9-hole Peg Test (9-HPT) score. EDSS = disability scale that ranges in 0.5-point steps from 0 \[normal\]-10.0 \[death\]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

769 participants

Primary outcome timeframe

Up to approximately 4.5 years

Results posted on

2026-07-24

Participant Flow

A total of 769 participants with primary progressive multiple sclerosis (PPMS) took part in the study at 149 investigative sites across 22 countries. The study is still ongoing.

Participants were randomized in a 2:1 ratio to receive treatment with either ocrelizumab higher dose (1200 milligrams \[mg\] or 1800 mg) based on the participant's body weight (BW) or ocrelizumab 600 mg for a minimum of up to 120 weeks. 16 participants were excluded from all analysis sets used in this study due to serious good clinical practice (GCP) violations. Therefore, results are presented for 753 participants.

Participant milestones

Participant milestones
Measure	Ocrelizumab 600 mg Participants received ocrelizumab, 600 mg, as an intravenous (IV) infusion, every 24 weeks (Q24W).	Ocrelizumab 1200 mg or 1800 mg Participants received ocrelizumab 1200 mg (BW \< 75 kilograms \[kg\]) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Overall Study STARTED	253	500
Overall Study Safety Analysis Set (SAS)	254	499
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	253	500

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocrelizumab 600 mg Participants received ocrelizumab, 600 mg, as an intravenous (IV) infusion, every 24 weeks (Q24W).	Ocrelizumab 1200 mg or 1800 mg Participants received ocrelizumab 1200 mg (BW \< 75 kilograms \[kg\]) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Overall Study Adverse Event	2	4
Overall Study Death	2	3
Overall Study Lost to Follow-up	1	3
Overall Study Reason not Specified	0	1
Overall Study Physician Decision	2	7
Overall Study Withdrawal by Subject	15	38
Overall Study Ongoing in Study	231	444

Baseline Characteristics

A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocrelizumab 600 mg n=253 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=500 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.	Total n=753 Participants Total of all reporting groups
Age, Continuous	41.7 years STANDARD_DEVIATION 8.9 • n=9 Participants	41.8 years STANDARD_DEVIATION 9.1 • n=27 Participants	41.8 years STANDARD_DEVIATION 9.0 • n=267 Participants
Sex: Female, Male Female	133 Participants n=9 Participants	266 Participants n=27 Participants	399 Participants n=267 Participants
Sex: Female, Male Male	120 Participants n=9 Participants	234 Participants n=27 Participants	354 Participants n=267 Participants
Race (NIH/OMB) American Indian or Alaska Native	9 Participants n=9 Participants	24 Participants n=27 Participants	33 Participants n=267 Participants
Race (NIH/OMB) Asian	1 Participants n=9 Participants	3 Participants n=27 Participants	4 Participants n=267 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=27 Participants	0 Participants n=267 Participants
Race (NIH/OMB) Black or African American	14 Participants n=9 Participants	10 Participants n=27 Participants	24 Participants n=267 Participants
Race (NIH/OMB) White	215 Participants n=9 Participants	444 Participants n=27 Participants	659 Participants n=267 Participants
Race (NIH/OMB) More than one race	3 Participants n=9 Participants	4 Participants n=27 Participants	7 Participants n=267 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=9 Participants	15 Participants n=27 Participants	26 Participants n=267 Participants
Race/Ethnicity, Customized Hispanic or Latino	34 Participants n=9 Participants	77 Participants n=27 Participants	111 Participants n=267 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	207 Participants n=9 Participants	404 Participants n=27 Participants	611 Participants n=267 Participants
Race/Ethnicity, Customized Unknown or Not Reported	3 Participants n=9 Participants	4 Participants n=27 Participants	7 Participants n=267 Participants
Race/Ethnicity, Customized Not Permitted	9 Participants n=9 Participants	15 Participants n=27 Participants	24 Participants n=267 Participants

PRIMARY outcome

Timeframe: Up to approximately 4.5 years

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=253 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=500 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)	158.7 weeks Interval 120.0 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.	169.0 weeks Interval 144.1 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned.

Time to onset of a 24 week cCDP=first occurrence of a 24-week cCDP according to at least 1 of 3 criteria: 1) CDP=24-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 24-week CI≥0.5 point in participants with baseline EDSS score of \>5.5 OR 2) 24-week CI of ≥20% FB in T25FWT score OR 3) 24-week CI of ≥ 20% FB in 9-HPT score. EDSS = disability scale that ranges in 0.5-point steps from 0 \[normal\]-10.0 \[death\]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=253 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=500 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of 24-week cCDP (cCDP24)	NA weeks Interval 144.1 to Median and upper limit of 95% confidence interval were not estimable due to insufficient number of participants with events.	NA weeks Interval 180.1 to Median and upper limit of 95% confidence interval were not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned.

Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of 3 criteria: 1) CDP=12-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of \>5.5 OR 2) 12-week CI of ≥20% FB in T25FWT score OR 3) 12-week CI of ≥ 20% FB in 9-HPT score. EDSS score, T25FWT \& 9-HPT are the same as defined in primary outcome measure. Protocol-defined relapse=occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. Symptoms persist for at least 24 hours \& accompanied by objective neurological worsening consistent with an increase of one of the following: Half a step (0.5 point) on the EDSS; Two points on one of the functional system scores (FSS) (pyramidal, ambulation, cerebellar, brainstem, sensory, or visual); One point on ≥2 more of the FSS.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=253 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=500 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) or Progression Independent of Relapse Activity (PIRA)	183.0 weeks Interval 120.1 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.	180.1 weeks Interval 145.0 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned.

CDP was defined as a 12-week confirmed increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a 12-week CI ≥0.5 points in participants with a baseline EDSS score of \>5.5. The EDSS was used to measure changes in the disability level of participants with MS over time. EDSS is based on a standard neurological examination, incorporating functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral \[or mental\]) that are rated and then scored as a FSS, and ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale where score range from 0 to 5 or 6, and ambulation score that is rated from 0 to 16. These ratings along with observations and assistive devices were then used to determine the total EDSS score. The total EDSS score ranges from 0 (normal) to 10.0 (death) in 0.5-point steps.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=253 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=500 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of 12-week Confirmed Disability Progression (CDP12)	NA weeks Median and 95% confidence interval were not estimable due to insufficient number of participants with events.	NA weeks Interval 214.1 to Median and upper limit of 95% confidence interval were not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned. Overall number analyzed is number of participants with data available for analysis.

T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. A 20% change from baseline of the averaged T25FWT was considered clinically meaningful.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=251 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=494 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to ≥ 20% Increase in 12-week Confirmed T25FWT	216.1 weeks Interval 173.0 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.	NA weeks Interval 192.4 to Median and upper limit of 95% confidence interval were not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

The SDMT is a performance measure that demonstrated sensitivity in detecting the presence of cognitive impairment and changes in cognitive functioning over time \& in response to treatment. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants were asked to pair specific numbers with given geometric figures within 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement. A four-point change from baseline was considered clinically meaningful.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=249 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=487 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of 12-week Confirmed ≥ 4-point Worsening in Symbol Digit Modalities Test (SDMT)	NA weeks Median and 95% confidence interval were not estimable due to insufficient number of participants with events.	226.1 weeks 95% confidence interval was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

The MSWS-12 was a 12-item self-report measure of the impact of MS on the participant's ability to walk during the past 2 weeks. Each item was scored on a 5-point Likert scale ranging from 1 (not at all) to 5 (extremely likely). Scores were summed and linearly converted to a 0-100 scale with higher scores indicating greater impact of MS on walking ability. An 8-point change was considered clinically meaningful.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=201 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=382 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Time to Onset of 24-week Confirmed ≥ 8-point Increase in 12-Item Multiple Sclerosis Walking Scale (MSWS-12)	NA weeks Interval 146.0 to Median and upper limit of 95% confidence interval were not estimable due to insufficient number of participants with events.	168.6 weeks Interval 146.0 to Upper limit of 95% confidence interval was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Brain volume was measured using magnetic resonance imaging (MRI) scans. Mean difference in annual rate of percent change from baseline in total brain volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=251 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=476 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Annual Rate of Percent Change From Baseline in Total Brain Volume	-0.480 percent change per year Standard Error 0.048	-0.548 percent change per year Standard Error 0.044

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Thalamic volume was measured using MRI scans. Mean difference in annual rate of percent change from baseline in thalamic volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=251 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=475 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Annual Rate of Percent Change From Baseline in Thalamic Volume	-0.974 percent change per year Standard Error 0.096	-1.006 percent change per year Standard Error 0.087

SECONDARY outcome

Timeframe: At Week 96

Population: FAS included all randomized participants, with participants grouped according to the treatment they were assigned. Overall number analyzed is the number of participants with data available for analysis.

NfL is a biomarker of neuroinflammation in CSF. Ratio of the mean change from baseline in NfL at Week 96 between the higher and approved dose of ocrelizumab arms in PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric means at Week 96 vs baseline).

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=197 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=382 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Ratio of Fold Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 96	0.78 ratio Interval 0.74 to 0.82	0.82 ratio Interval 0.79 to 0.85

SECONDARY outcome

Timeframe: At Week 96

NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab higher dose group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=382 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Fold Change From Baseline in NfL Levels at Week 96 Within the Higher Dose Ocrelizumab Group	0.82 ratio Interval 0.79 to 0.85	—

SECONDARY outcome

Timeframe: At Week 96

NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab 600 mg group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=197 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Fold Change From Baseline in NfL Levels at Week 96 Within the Approved Dose Ocrelizumab Group	0.78 ratio Interval 0.74 to 0.82	—

SECONDARY outcome

Timeframe: From initiation of study drug up to approximately 6.8 years

AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to Week 24

Population: Pharmacokinetic (PK) analysis set included all participants who had measurable concentrations of ocrelizumab. Number analyzed is the number of participants with data available for analysis for a specific dose.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=254 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=499 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Area Under the Serum Concentration-time Curve (AUC) of Ocrelizumab Over the First Dosing Interval 600 mg	2740 micrograms/milliliterday (µg/mLday) Geometric Coefficient of Variation 0.37	—
Area Under the Serum Concentration-time Curve (AUC) of Ocrelizumab Over the First Dosing Interval 1200 mg	—	6410 micrograms/milliliterday (µg/mLday) Geometric Coefficient of Variation 0.202
Area Under the Serum Concentration-time Curve (AUC) of Ocrelizumab Over the First Dosing Interval 1800 mg	—	7100 micrograms/milliliterday (µg/mLday) Geometric Coefficient of Variation 0.269

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

Population: SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=254 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=492 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
B-cell Levels in Blood Baseline	260.23 cells/microliters (cells/μL) Standard Deviation 177.83	249.25 cells/microliters (cells/μL) Standard Deviation 135.00
B-cell Levels in Blood Week 96	8.55 cells/microliters (cells/μL) Standard Deviation 31.87	6.29 cells/microliters (cells/μL) Standard Deviation 39.04
B-cell Levels in Blood Week 120	7.76 cells/microliters (cells/μL) Standard Deviation 28.50	10.37 cells/microliters (cells/μL) Standard Deviation 93.01
B-cell Levels in Blood Week 144	9.38 cells/microliters (cells/μL) Standard Deviation 41.26	4.66 cells/microliters (cells/μL) Standard Deviation 21.56
B-cell Levels in Blood Week 2	5.95 cells/microliters (cells/μL) Standard Deviation 34.21	3.75 cells/microliters (cells/μL) Standard Deviation 25.71
B-cell Levels in Blood Week 24	12.47 cells/microliters (cells/μL) Standard Deviation 36.53	5.77 cells/microliters (cells/μL) Standard Deviation 16.90
B-cell Levels in Blood Week 48	12.49 cells/microliters (cells/μL) Standard Deviation 39.92	7.58 cells/microliters (cells/μL) Standard Deviation 26.88
B-cell Levels in Blood Week 72	13.81 cells/microliters (cells/μL) Standard Deviation 45.56	9.58 cells/microliters (cells/μL) Standard Deviation 78.06
B-cell Levels in Blood Week 168	4.40 cells/microliters (cells/μL) Standard Deviation 18.26	9.07 cells/microliters (cells/μL) Standard Deviation 71.97
B-cell Levels in Blood Week 192	4.47 cells/microliters (cells/μL) Standard Deviation 17.75	4.60 cells/microliters (cells/μL) Standard Deviation 33.04
B-cell Levels in Blood Week 216	3.43 cells/microliters (cells/μL) Standard Deviation 7.97	0.73 cells/microliters (cells/μL) Standard Deviation 0.83

SECONDARY outcome

Timeframe: Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=231 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=447 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Percent Change From Baseline in B-cell Levels Change at Week 216	-98.24 percent change Standard Deviation 4.33	-99.73 percent change Standard Deviation 0.32
Percent Change From Baseline in B-cell Levels Change at Week 24	-94.62 percent change Standard Deviation 18.44	-96.85 percent change Standard Deviation 11.87
Percent Change From Baseline in B-cell Levels Change at Week 48	-95.19 percent change Standard Deviation 12.21	-94.51 percent change Standard Deviation 34.39
Percent Change From Baseline in B-cell Levels Change at Week 72	-93.54 percent change Standard Deviation 23.55	-93.88 percent change Standard Deviation 61.26
Percent Change From Baseline in B-cell Levels Change at Week 168	-97.62 percent change Standard Deviation 11.47	-94.29 percent change Standard Deviation 54.94
Percent Change From Baseline in B-cell Levels Change at Week 192	-97.95 percent change Standard Deviation 9.02	-98.40 percent change Standard Deviation 9.90
Percent Change From Baseline in B-cell Levels Change at Week 2	-97.66 percent change Standard Deviation 11.25	-97.55 percent change Standard Deviation 23.32
Percent Change From Baseline in B-cell Levels Change at Week 96	-96.53 percent change Standard Deviation 13.83	-94.89 percent change Standard Deviation 45.13
Percent Change From Baseline in B-cell Levels Change at Week 120	-97.07 percent change Standard Deviation 9.20	-93.55 percent change Standard Deviation 67.99
Percent Change From Baseline in B-cell Levels Change at Week 144	-97.31 percent change Standard Deviation 7.93	-97.72 percent change Standard Deviation 11.81

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=254 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=492 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Baseline	0 percentage of participants	0.4 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 2	96.1 percentage of participants	95.8 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 72	78.4 percentage of participants	87.3 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 96	80.4 percentage of participants	89.1 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 120	82.8 percentage of participants	90.8 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 144	85.5 percentage of participants	93.5 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 168	86.8 percentage of participants	93.1 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 24	68.4 percentage of participants	81.2 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 48	75.7 percentage of participants	82.5 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 192	88.1 percentage of participants	96.6 percentage of participants
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood Week 216	90.9 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=254 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=492 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 24	5.7 percentage of participants	9.4 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 48	8.6 percentage of participants	12.4 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 72	12.3 percentage of participants	18.2 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 96	16.8 percentage of participants	30.4 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 120	20.0 percentage of participants	30.8 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 144	23.9 percentage of participants	41.4 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 168	34.9 percentage of participants	41.7 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 192	45.2 percentage of participants	46.1 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 216	27.3 percentage of participants	63.6 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Week 2	23.8 percentage of participants	30.2 percentage of participants
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood Baseline	0 percentage of participants	0.2 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: Immunogenicity analysis set included all participants with at least one ADA assessment, with participants grouped according to treatment received. Overall number analyzed is the number of participants with data available for analysis.

Participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer unit (t.u.) greater than the baseline titer result. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Ocrelizumab 600 mg n=252 Participants Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=491 Participants Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
Percentage of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab	1.6 percentage of participants	0.8 percentage of participants

Adverse Events

Ocrelizumab 600 mg

Serious events: 29 serious events

Other events: 176 other events

Deaths: 3 deaths

Ocrelizumab 1200 mg or 1800 mg

Serious events: 61 serious events

Other events: 381 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ocrelizumab 600 mg n=254 participants at risk Participants received ocrelizumab, 600 mg, as an IV infusion, Q24W.	Ocrelizumab 1200 mg or 1800 mg n=499 participants at risk Participants received ocrelizumab 1200 mg (BW \< 75 kg) or 1800 mg (BW ≥ 75 kg), as an IV infusion, Q24W.
General disorders Fatigue	3.5% 9/254 • Number of events 9 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	6.0% 30/499 • Number of events 37 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations COVID-19	17.7% 45/254 • Number of events 51 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	16.2% 81/499 • Number of events 95 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Influenza	5.1% 13/254 • Number of events 19 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	5.6% 28/499 • Number of events 34 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Nasopharyngitis	15.7% 40/254 • Number of events 57 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	16.8% 84/499 • Number of events 129 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Respiratory tract infection	7.1% 18/254 • Number of events 25 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	2.6% 13/499 • Number of events 14 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Respiratory tract infection viral	5.5% 14/254 • Number of events 27 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	7.0% 35/499 • Number of events 73 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Upper respiratory tract infection	10.6% 27/254 • Number of events 43 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	15.2% 76/499 • Number of events 112 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Infections and infestations Urinary tract infection	10.2% 26/254 • Number of events 53 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	16.2% 81/499 • Number of events 153 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Injury, poisoning and procedural complications Fall	7.5% 19/254 • Number of events 32 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	9.4% 47/499 • Number of events 87 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Injury, poisoning and procedural complications Infusion related reaction	23.2% 59/254 • Number of events 94 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	23.6% 118/499 • Number of events 180 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 18/254 • Number of events 18 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	6.6% 33/499 • Number of events 40 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Musculoskeletal and connective tissue disorders Back pain	7.5% 19/254 • Number of events 22 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	10.2% 51/499 • Number of events 62 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Nervous system disorders Headache	14.2% 36/254 • Number of events 57 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	13.0% 65/499 • Number of events 141 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Psychiatric disorders Depression	6.7% 17/254 • Number of events 18 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	7.0% 35/499 • Number of events 36 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.
Psychiatric disorders Insomnia	4.7% 12/254 • Number of events 12 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.	6.2% 31/499 • Number of events 33 • From initiation of study drug up to approximately 4.5 years SAS included all participants who received at least one infusion (partial or complete) of the study drug, with participants grouped according to the treatment they received. 1 participant in the higher dose ocrelizumab arm received ocrelizumab 600 mg and was therefore included in the safety analyses for the ocrelizumab 600 mg arm. Data collection is still ongoing, and final data will be reported one year after the study completion date.