Trial Outcomes & Findings for A Phase III, Non-Inferiority, Randomized, Open-Label, Parallel Group, Multicenter Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis (NCT NCT05232825)

NCT ID: NCT05232825

Last Updated: 2026-08-11

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

236 participants

Primary outcome timeframe

Day 1 Week 1 to Week 12

Results posted on

2026-08-11

Participant Flow

A total of 236 participants with primary progressive multiple sclerosis (PPMS) or relapsing multiple sclerosis (RMS) took part in the study at 37 investigative sites across 8 countries from 03 May 2022 to 06 June 2025.

The study consisted of 3 periods: a 24-week controlled period, where participants were randomized in a 1:1 ratio to receive ocrelizumab as either subcutaneous (SC) injection or intravenous (IV) infusion, an ocrelizumab SC treatment period, where participants in both arms received SC treatment, followed by a safety follow-up period where participants who completed the treatment or discontinued from the treatment early were followed for up to 24 weeks after the last ocrelizumab administration.

Participant milestones

Participant milestones
Measure	Ocrelizumab IV Participants received ocrelizumab, 300 milligrams (mg), as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered the safety follow-up (SFU) period.	Ocrelizumab SC Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Controlled Period STARTED	118	118
Controlled Period COMPLETED	115	118
Controlled Period NOT COMPLETED	3	0
Ocrelizumab SC Treatment Period STARTED	115	118
Ocrelizumab SC Treatment Period COMPLETED	109	110
Ocrelizumab SC Treatment Period NOT COMPLETED	6	8
SFU Period STARTED	113	115
SFU Period COMPLETED	112	115
SFU Period NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocrelizumab IV Participants received ocrelizumab, 300 milligrams (mg), as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered the safety follow-up (SFU) period.	Ocrelizumab SC Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Controlled Period Discontinued and Entered SFU Period	2	0
Controlled Period Physician Decision	1	0
Ocrelizumab SC Treatment Period Discontinued and Entered SFU Period	2	5
Ocrelizumab SC Treatment Period Withdrawal by Subject	3	3
Ocrelizumab SC Treatment Period Adverse Event	1	0
SFU Period Lost to Follow-up	1	0

Baseline Characteristics

A Phase III, Non-Inferiority, Randomized, Open-Label, Parallel Group, Multicenter Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocrelizumab IV n=118 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Total n=236 Participants Total of all reporting groups
Race (NIH/OMB) More than one race	1 Participants n=54 Participants	3 Participants n=54 Participants	4 Participants n=27 Participants
Age, Continuous	40.0 years STANDARD_DEVIATION 11.9 • n=54 Participants	39.9 years STANDARD_DEVIATION 11.4 • n=54 Participants	39.9 years STANDARD_DEVIATION 11.6 • n=27 Participants
Sex: Female, Male Female	70 Participants n=54 Participants	77 Participants n=54 Participants	147 Participants n=27 Participants
Sex: Female, Male Male	48 Participants n=54 Participants	41 Participants n=54 Participants	89 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=54 Participants	8 Participants n=54 Participants	16 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	93 Participants n=54 Participants	94 Participants n=54 Participants	187 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=54 Participants	16 Participants n=54 Participants	33 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=54 Participants	0 Participants n=54 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=54 Participants	0 Participants n=54 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=54 Participants	0 Participants n=54 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=54 Participants	7 Participants n=54 Participants	8 Participants n=27 Participants
Race (NIH/OMB) White	109 Participants n=54 Participants	102 Participants n=54 Participants	211 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=54 Participants	6 Participants n=54 Participants	11 Participants n=27 Participants

PRIMARY outcome

Timeframe: Day 1 Week 1 to Week 12

Population: Pharmacokinetic (PK)-evaluable set included all participants who received the full assigned dose of ocrelizumab and had measurable serum concentrations of ocrelizumab, grouped according to the actual dose and actual route of administration.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=116 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=116 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration	2750 micrograms/millilitersday (µg/mLday) Standard Deviation 796	3500 micrograms/millilitersday (µg/mLday) Standard Deviation 914

SECONDARY outcome

Timeframe: Day 1 Week 1 to Week 24

Population: PK-evaluable set included all participants who received the full assigned dose of ocrelizumab and had measurable serum concentrations of ocrelizumab, grouped according to the actual dose and actual route of administration.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=116 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=116 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Maximum Serum Concentration (Cmax) of Ocrelizumab SC	137 micrograms/milliliters (µg/mL) Standard Deviation 29.5	132 micrograms/milliliters (µg/mL) Standard Deviation 31.9

SECONDARY outcome

Timeframe: At Weeks 8 and 24

Population: EE-MRI set included all randomized participants who received, during the controlled period (i.e., time until Week 24 dose of ocrelizumab SC), at least 1 infusion or injection (partial/complete) of study drug \& had at least 1 brain MRI scan taken, grouped according to the treatment they were assigned. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Radiologic evaluation for the total number of T1Gd+ lesions was performed using a standardized MRI at Weeks 8 and 24 to monitor central nervous system (CNS) lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable \& was adjusted for covariates: baseline T1Gd+ lesion (present or not), geographical region (United States of America vs. Rest of the world). EE = Efficacy-evaluable.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=118 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) at Weeks 8 and 24 At Week 8	0.060 lesions per participant Interval 0.02 to 0.15	0.060 lesions per participant Interval 0.02 to 0.14
Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) at Weeks 8 and 24 At Week 24	0.000 lesions per participant Interval 0.0 to Upper limit of 95% CI was not estimable due to the low number of lesions at Week 24.	0.000 lesions per participant Interval 0.0 to Upper limit of 95% CI was not estimable due to the low number of lesions at Week 24.

SECONDARY outcome

Timeframe: At Weeks 12 and 24

Radiologic evaluation for the new or enlarging T2 lesions was performed using a standardized MRI at Weeks 12 and 24 to monitor CNS lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable \& was adjusted for covariates: baseline T2 lesion count, geographical region (United States of America vs. Rest of the world).

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=118 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Rate of New or Enlarging T2 Lesions as Detected by Brain MRI at Weeks 12 and 24 At Week 12	0.050 lesions per participant Interval 0.01 to 0.17	0.020 lesions per participant Interval 0.0 to 0.1
Rate of New or Enlarging T2 Lesions as Detected by Brain MRI at Weeks 12 and 24 At Week 24	0.000 lesions per participant Interval 0.0 to 0.0	0.000 lesions per participant Interval 0.0 to 0.01

SECONDARY outcome

Timeframe: From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks)

An 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 measures
Measure	Ocrelizumab IV n=118 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Number of Participants With Adverse Events (AEs)	101 Participants	111 Participants

SECONDARY outcome

Timeframe: Up to 138.1 weeks

Population: Immunogenicity - evaluable - all set included all randomized participants with at least one ADA assessment, with participants grouped according to treatment received at first exposure or, if no treatment is received prior to study discontinuation, according to the treatment they were assigned.

Participants who received ocrelizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=118 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab After SC or IV Administration	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 138.1 weeks

Ocrelizumab SC formulation is co-formulated with rHuPH20 at a concentration of 1000 units per milliliter (U/mL). Participants who received ocrelizumab SC were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab SC exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=117 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Number of Participants With ADAs to rHuPH20 After Ocrelizumab SC Administration	1 Participants	4 Participants

SECONDARY outcome

Timeframe: At Weeks 12, 24, 48, and 96

Population: SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug, grouped according to treatment received at first exposure. 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.

B-cells were assessed in fresh whole blood using flow cytometry. Percentages have been rounded off.

Outcome measures

Outcome measures
Measure	Ocrelizumab IV n=115 Participants Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=115 Participants Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96 At Week 12	98.3 percentage of participants	98.3 percentage of participants
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96 At Week 24	78.9 percentage of participants	74.6 percentage of participants
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96 At Week 48	92.0 percentage of participants	86.0 percentage of participants
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96 At Week 96	92.5 percentage of participants	90.7 percentage of participants

Adverse Events

Ocrelizumab IV

Serious events: 9 serious events

Other events: 86 other events

Deaths: 0 deaths

Ocrelizumab SC

Serious events: 7 serious events

Other events: 99 other events

Deaths: 0 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 IV n=118 participants at risk Participants received ocrelizumab, 300 mg, as IV infusions on Day 1 Week 1, and Day 14 Week 2 of the controlled period, followed by ocrelizumab co-formulated with rHuPH20, 920 mg as SC injections at Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.	Ocrelizumab SC n=118 participants at risk Participants received ocrelizumab co-formulated with rHuPH20, 920 mg as SC injection on Day 1 of the controlled period and on Weeks 24, 48, 72, and 96 of the ocrelizumab SC treatment period. Participants who completed the treatment period or discontinued early entered SFU period.
Injury, poisoning and procedural complications Injection related reaction	46.6% 55/118 • Number of events 124 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	62.7% 74/118 • Number of events 189 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Upper respiratory tract infection	15.3% 18/118 • Number of events 35 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	15.3% 18/118 • Number of events 30 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Urinary tract infection	10.2% 12/118 • Number of events 16 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	12.7% 15/118 • Number of events 19 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Injury, poisoning and procedural complications Infusion related reaction	16.9% 20/118 • Number of events 27 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	0.00% 0/118 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Bronchitis	7.6% 9/118 • Number of events 13 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	8.5% 10/118 • Number of events 12 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations COVID-19	10.2% 12/118 • Number of events 13 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	16.1% 19/118 • Number of events 22 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Nasopharyngitis	5.1% 6/118 • Number of events 7 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	9.3% 11/118 • Number of events 14 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Nervous system disorders Headache	5.1% 6/118 • Number of events 6 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	11.0% 13/118 • Number of events 35 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Influenza	4.2% 5/118 • Number of events 6 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.1% 6/118 • Number of events 7 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Oral herpes	0.85% 1/118 • Number of events 1 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.9% 7/118 • Number of events 9 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Pharyngitis	3.4% 4/118 • Number of events 5 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.9% 7/118 • Number of events 8 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Rhinitis	0.85% 1/118 • Number of events 2 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	8.5% 10/118 • Number of events 10 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Infections and infestations Sinusitis	3.4% 4/118 • Number of events 5 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.9% 7/118 • Number of events 7 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Injury, poisoning and procedural complications Fall	5.9% 7/118 • Number of events 11 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	3.4% 4/118 • Number of events 7 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 7/118 • Number of events 10 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	2.5% 3/118 • Number of events 3 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Musculoskeletal and connective tissue disorders Back pain	3.4% 4/118 • Number of events 4 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.1% 6/118 • Number of events 6 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 3/118 • Number of events 4 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	5.1% 6/118 • Number of events 6 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).
Psychiatric disorders Depression	5.9% 7/118 • Number of events 8 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).	2.5% 3/118 • Number of events 3 • From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks) SE- all set included all randomized participants who received at least one infusion (partial or complete) or injection (partial or complete) of study drug (IV or SC ocrelizumab). As pre-specified in Section 6.5 Protocol Version 4 (United States), participants were grouped for the safety analyses according to the treatment received at first exposure (IV or SC ocrelizumab).