Trial Outcomes & Findings for A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT) (NCT NCT02637856)

Last Updated: 2020-05-26

Results Overview

Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 gadolinium (Gd)-enhanced lesion on brain magnetic resonance imaging (MRI) or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

608 participants

Primary outcome timeframe

Baseline up to Week 96

Results posted on

2020-05-26

Participant Flow

The study was conducted in North America at 90 study sites in the U.S. and Canada.

Participants with relapsing remitting multiple sclerosis (RRMS) were enrolled, who had had a suboptimal response to an adequate course of a disease-modifying treatment (DMT). An adequate course of prior DMT was defined as the same DMT administered for at least 6 months.

Participant milestones

Participant milestones
Measure	Ocrelizumab Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)	Ocrelizumab (Substudy) Participants who completed their Week 72 ocrelizumab infusion and did not experience any serious infusion related reactions (IRRs) throughout the main study were eligible to enroll in an optional substudy and received one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab was administered as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Main Study (Baseline to Week 100) STARTED	608	0
Main Study (Baseline to Week 100) COMPLETED	389	0
Main Study (Baseline to Week 100) NOT COMPLETED	219	0
Sub-Study (Week 72 to Week 100) STARTED	0	129
Sub-Study (Week 72 to Week 100) COMPLETED	0	125
Sub-Study (Week 72 to Week 100) NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocrelizumab Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)	Ocrelizumab (Substudy) Participants who completed their Week 72 ocrelizumab infusion and did not experience any serious infusion related reactions (IRRs) throughout the main study were eligible to enroll in an optional substudy and received one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab was administered as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Main Study (Baseline to Week 100) Adverse Event	9	0
Main Study (Baseline to Week 100) Lost to Follow-up	5	0
Main Study (Baseline to Week 100) Physician Decision	2	0
Main Study (Baseline to Week 100) Pregnancy	7	0
Main Study (Baseline to Week 100) Withdrawal by Subject	20	0
Main Study (Baseline to Week 100) Protocol Deviation	2	0
Main Study (Baseline to Week 100) Continued on Commercial Ocrevus	164	0
Main Study (Baseline to Week 100) Failed Drug Test	1	0
Main Study (Baseline to Week 100) Incarceration	1	0
Main Study (Baseline to Week 100) Pregnancy Attempts	2	0
Main Study (Baseline to Week 100) Site Closing	6	0
Sub-Study (Week 72 to Week 100) Non-safety reason (moved out of state)	0	1
Sub-Study (Week 72 to Week 100) Lost to Follow-up	0	3

Baseline Characteristics

A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Age, Continuous	37.2 Years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	438 Participants n=5 Participants
Sex: Female, Male Male	170 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	68 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	526 Participants n=5 Participants
Race/Ethnicity, Customized Not Stated	7 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	17 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	13 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	72 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	6 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islande	3 Participants n=5 Participants
Race/Ethnicity, Customized White	495 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 96

Population: The modified Intent-to-Treat (mITT) population was a subset of the ITT population which excluded participants who discontinued ocrelizumab treatment early without any protocol-defined events for reasons other than death and lack of efficacy. Only participants for whom data were collected are included in the analysis.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Percentage of Participants Without Any Protocol-Defined Events During 96-Week Period	48.1 Percentage of Participants Interval 43.9 to 52.3

PRIMARY outcome

Timeframe: Week 96 to Week 100

Population: Participants who completed their Week 72 ocrelizumab infusion and did not experience any serious IRRs throughout the main study

Rate and frequency of Grade 3 or 4 IRRs with onset on or after the shorter ocrelizumab infusion

Outcome measures

Outcome measures
Measure	Ocrelizumab n=129 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Percentage of Participants With Infusion Related Reactions (IRRs) in Optional Substudy	0 Percentage of Participants Interval 0.0 to 2.8

SECONDARY outcome

Timeframe: Baseline up to Weeks 24 and 48

Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period Week 24	59.0 Percentage of Participants Interval 54.9 to 63.1
Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period Week 48	51.2 Percentage of Participants Interval 47.0 to 55.4

SECONDARY outcome

Timeframe: Baseline up to Week 96

Population: All enrolled participants who received any ocrelizumab. Participants who prematurely withdrew from the study for any reason and who did not have any assessments for any reason were still included in the ITT population as long as the participant received ocrelizumab

Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Time to Protocol-Defined Event	NA Weeks Interval 53.86 to Not estimable because more than 50% of the ITT population were event-free at the end of the study

SECONDARY outcome

Timeframe: Baseline up to Week 96

Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for greater than (\>) 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days. The Adjusted Annualized Relapse Rate was adjusted by baseline Expanded Disability Status Scale (EDSS \<2.5 vs. \>=2.5) and number of previous disease-modifying treatments (DMTs =1 vs. \>1)

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Total Number of Protocol-Defined Relapses Per Participant Year During 96-week Period	0.046 Number of Relapses/Participant Year Interval 0.036 to 0.06

SECONDARY outcome

Timeframe: Baseline up to Week 96

Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for \>24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Time to Onset of First Protocol-Defined Relapse	NA Weeks Not estimable because more than 50% of the ITT population were event-free at the end of the study

SECONDARY outcome

Timeframe: Baseline up to Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI	NA Weeks Not estimable because more than 50% of the ITT population were event-free at the end of the study

SECONDARY outcome

Timeframe: Baseline up to Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI	NA Weeks Not estimable because more than 50% of the ITT population were event-free at the end of the study

SECONDARY outcome

Timeframe: Baseline up to Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks According to Expanded Disability Status Scale (EDSS) Score	NA Weeks Not estimable because more than 50% of the ITT population were event-free at the end of the study

SECONDARY outcome

Timeframe: Weeks 24, 48, and 96

The analyses included participants who had an interpretable MRI at the time point of interest. Participants having 0, 1, 2, 3, and greater than 3 lesions at weeks 24, 48, and 96 were included in the analysis.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 24	33 Number of Lesions Interval 0.01 to 0.05
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 48	16 Number of Lesions Interval 0.002 to 0.031
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 96	7 Number of Lesions Interval 0.002 to 0.026

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48, and 96

Baseline data is represented as mean; post-Baseline date are represented as mean changes.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI Baseline	11.551 cubic centimeter (cm3) Standard Error 0.590
Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI Week 24	-0.484 cubic centimeter (cm3) Standard Error 0.118
Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI Week 48	-0.549 cubic centimeter (cm3) Standard Error 0.123
Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI Week 96	-0.560 cubic centimeter (cm3) Standard Error 0.129

SECONDARY outcome

Timeframe: Weeks 24, 48, and 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI Week 96	38 Number of Lesions
Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI Week 24	640 Number of Lesions
Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI Week 48	39 Number of Lesions

SECONDARY outcome

Timeframe: Baseline up to 100 weeks

An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=608 Participants Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)
Percentage of Participants With Adverse Events	86.3 Percentage of Participants

Adverse Events

Ocrelizumab

Serious events: 47 serious events

Other events: 406 other events

Deaths: 0 deaths

Ocrelizumab (Substudy)

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ocrelizumab n=608 participants at risk Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)	Ocrelizumab (Substudy) n=129 participants at risk Participants who completed their Week 72 ocrelizumab infusion and did not experience any serious infusion related reactions (IRRs) throughout the main study were eligible to enroll in an optional substudy and received one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab was administered as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Gastrointestinal disorders Nausea	5.3% 32/608 • Number of events 38 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
General disorders Fatigue	9.5% 58/608 • Number of events 62 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Nasopharyngitis	10.5% 64/608 • Number of events 81 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Sinusitis	6.1% 37/608 • Number of events 47 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Upper respiratory tract infection	9.4% 57/608 • Number of events 76 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Urinary tract infection	14.5% 88/608 • Number of events 118 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Infusion related reaction	43.3% 263/608 • Number of events 519 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	12.4% 16/129 • Number of events 16 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 36/608 • Number of events 41 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Headache	9.2% 56/608 • Number of events 66 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.

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 n=608 participants at risk Participants received ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks)	Ocrelizumab (Substudy) n=129 participants at risk Participants who completed their Week 72 ocrelizumab infusion and did not experience any serious infusion related reactions (IRRs) throughout the main study were eligible to enroll in an optional substudy and received one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab was administered as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Blood and lymphatic system disorders Anaemia	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Blood and lymphatic system disorders Leukopenia	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Cardiac disorders Atrial fibrillation	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Cardiac disorders Wolff-Parkinson-White syndrome	0.16% 1/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Ear and labyrinth disorders Mastoid effusion	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Gastrointestinal disorders Abdominal pain	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Gastrointestinal disorders Abdominal pain lower	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Gastrointestinal disorders Crohn's disease	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Gastrointestinal disorders Pancreatitis	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Gastrointestinal disorders Vomiting	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
General disorders Chest pain	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
General disorders Systemic inflammatory response syndrome	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Hepatobiliary disorders Cholecystitis	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Hepatobiliary disorders Cholecystitis acute	0.33% 2/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Immune system disorders Anaphylactic reaction	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Immune system disorders Drug hypersensitivity	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Appendicitis	0.49% 3/608 • Number of events 3 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Gastroenteritis viral	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Kidney infection	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Pyelonephritis	0.33% 2/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Infections and infestations Urinary tract infection	0.33% 2/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Ankle fracture	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Fall	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Lower limb fracture	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Multiple injuries	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Road traffic accident	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Injury, poisoning and procedural complications Subdural haematoma	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Musculoskeletal and connective tissue disorders Muscle spasms	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.78% 1/129 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of the cervix	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.78% 1/129 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Encephalopathy	0.33% 2/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Multiple sclerosis relapse	0.49% 3/608 • Number of events 3 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Neuralgia	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Seizure	0.33% 2/608 • Number of events 3 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Syncope	0.33% 2/608 • Number of events 2 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Nervous system disorders Trigeminal neuralgia	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Psychiatric disorders Depression	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Psychiatric disorders Suicidal ideation	0.49% 3/608 • Number of events 3 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Psychiatric disorders Suicide attempt	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Renal and urinary disorders Nephrolithiasis	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Respiratory, thoracic and mediastinal disorders Asthma	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Surgical and medical procedures Cardiac ablation	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.
Vascular disorders Fibromuscular dysplasia	0.16% 1/608 • Number of events 1 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.	0.00% 0/129 • Baseline up to 100 weeks The Safety Population included all enrolled participants who received any ocrelizumab.