Trial Outcomes & Findings for Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS) (NCT NCT03085810)

Last Updated: 2025-01-15

Results Overview

The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1225 participants

Primary outcome timeframe

Baseline up to 4 years

Results posted on

2025-01-15

Participant Flow

A prospective, multicenter, open-label, single-arm effectiveness and safety study enrolled 1225 eligible treatment-naive patients with early stage RMSR. The study consisted of screening period up 4 weeks and open-label treatment with ocrelizumab period up to 192 week.

The efficacy analyses were performed on the main study cohort enrolled as per original study protocol, and safety analyses on all enrolled participants.

Participant milestones

Participant milestones
Measure	Main Study - Ocrelizumab Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period.	Substudy - Conventional Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 3.5 hours every 24 weeks throughout the treatment period.	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Main Study STARTED	1225	0	0
Main Study COMPLETED	1010	0	0
Main Study NOT COMPLETED	215	0	0
Substudy (Week 24 to Week 144) STARTED	0	373	372
Substudy (Week 24 to Week 144) COMPLETED	0	0	2
Substudy (Week 24 to Week 144) NOT COMPLETED	0	373	370

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study - Ocrelizumab Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period.	Substudy - Conventional Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 3.5 hours every 24 weeks throughout the treatment period.	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Main Study Withdrawal by Subject	77	0	0
Main Study Terminated By Sponsor	14	0	0
Main Study Protocol Violation	15	0	0
Main Study Physician Decision	13	0	0
Main Study Lost to Follow-up	17	0	0
Main Study Adverse Event	25	0	0
Main Study Pregnancy	7	0	0
Main Study Changed to Commercial Ocrelizumab	4	0	0
Main Study Lack of Efficacy	10	0	0
Main Study Death	12	0	0
Main Study Disease progression	1	0	0
Main Study Site Closure	3	0	0
Main Study Planned pregnancy	17	0	0
Substudy (Week 24 to Week 144) Withdrawal due to Infusion Related Reaction (IRR)	0	0	3
Substudy (Week 24 to Week 144) Withdrawal by Subject	0	5	7
Substudy (Week 24 to Week 144) Substudy Stopped by Sponsor	0	355	352
Substudy (Week 24 to Week 144) Reason Not Specified	0	13	8

Baseline Characteristics

Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocrelizumab n=1225 Participants Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period
Age, Continuous	32.7 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	784 Participants n=5 Participants
Sex: Female, Male Male	441 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	960 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	120 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	11 Participants n=5 Participants
Race (NIH/OMB) Asian	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	34 Participants n=5 Participants
Race (NIH/OMB) White	1007 Participants n=5 Participants
Race (NIH/OMB) More than one race	37 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	115 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 4 years

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS) CPD Sustained for at Least 24 weeks	NA weeks Median (corresponds to a probability of 50%) and 95% CI was not reached due to low number of participants with the event at the end of the study.	—
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS) CDP Sustained for at Least 48 weeks	NA weeks Median (corresponds to a probability of 50%) and 95% CI was not reached due to low number of participants with the event at the end of the study.	—

PRIMARY outcome

Timeframe: At Weeks 24 and 48 during Year 1

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.

CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).

Outcome measures

Outcome measures
Measure	Ocrelizumab n=309 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 24	95.11 Percentage of Participants Interval 92.03 to 97.03	—
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 48	83.50 Percentage of Participants Interval 78.81 to 87.24	—
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 48	87.54 Percentage of Participants Interval 83.28 to 90.77	—

PRIMARY outcome

Timeframe: Year 1 (Weeks 24 and 48)

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed for CDP at that timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS CDP Sustained for 24 weeks: At Week 48	97.30 Percentage of Participants Interval 95.75 to 98.29	—
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS CDP Sustained for 48 weeks: At Week 48	98.05 Percentage of Participants Interval 96.67 to 98.87	—
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS CDP Sustained for 24 weeks: At Week 24	99.55 Percentage of Participants Interval 98.62 to 99.86	—

PRIMARY outcome

Timeframe: At Weeks 48, 72 and 96 during Year 2

CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).

Outcome measures

Outcome measures
Measure	Ocrelizumab n=252 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 96	90.29 Percentage of Participants Interval 85.71 to 93.46	—
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 96	92.55 Percentage of Participants Interval 88.41 to 92.55	—
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 72:	97.20 Percentage of Participants Interval 94.22 to 98.66	—
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 72	97.60 Percentage of Participants Interval 94.74 to 98.91	—
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 48	100.0 Percentage of Participants Interval 100.0 to 100.0	—
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 48	100.00 Percentage of Participants Interval 100.0 to 100.0	—

PRIMARY outcome

Timeframe: Year 2 (Weeks 72 and 96)

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS CDP Sustained for 24 weeks: At Week 72	93.97 Percentage of Particiopants Interval 91.87 to 95.54	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS CDP Sustained for 48 weeks: At Week 72	95.18 Percentage of Particiopants Interval 93.25 to 96.56	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS CDP Sustained for 24 weeks: Week 96	91.65 Percentage of Particiopants Interval 89.26 to 93.52	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS CDP Sustained for 48 weeks: Week 96	93.47 Percentage of Particiopants Interval 91.3 to 95.12	—

PRIMARY outcome

Timeframe: At Weeks 144, 168 and 192 during Year 4

CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 144	100.00 Percentage of Participants Interval 100.0 to 100.0	—
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 144	100.00 Percentage of Participants Interval 100.0 to 100.0	—
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 168	99.54 Percentage of Participants Interval 96.77 to 99.93	—
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 168	100.00 Percentage of Participants Interval 100.0 to 100.0	—
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 24 weeks: At Week 192	93.77 Percentage of Participants Interval 89.51 to 96.34	—
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS CDI Sustained for 48 weeks: At Week 192	98.01 Percentage of Participants Interval 94.77 to 99.25	—

PRIMARY outcome

Timeframe: Year 4 (Weeks 168 and 192)

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS CDP Sustained for 24 weeks: At Week 168	85.98 Percentage of Participants Interval 83.04 to 88.44	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS CDP Sustained for 48 weeks: At Week 168	87.98 Percentage of Participants Interval 85.2 to 90.27	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS CDP Sustained for 24 weeks: At Week 192	84.18 Percentage of Participants Interval 81.08 to 86.81	—
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS CDP Sustained for 48 weeks: At Week 192	86.48 Percentage of Participants Interval 83.54 to 88.93	—

PRIMARY outcome

Timeframe: Year 1 (Week 48)

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=659 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS Week 48 Worsened (>0.5)	9.3 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS Week 48 Stable (Change <= 0.5 and >= -0.5)	73.3 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS Week 48 Improved (<-0.5)	17.5 Percentage of Participants	—

PRIMARY outcome

Timeframe: Year 2 (Week 96)

Outcome measures

Outcome measures
Measure	Ocrelizumab n=632 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS Week 96 Worsened (>0.5)	11.9 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS Week 96 Stable (Change <= 0.5 and >= -0.5)	76.6 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS Week 96 Improved (<-0.5)	11.6 Percentage of Participants	—

PRIMARY outcome

Timeframe: Year 3

Outcome measures

Outcome measures
Measure	Ocrelizumab n=557 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS Worsened (>0.5)	9.3 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS Stable (Change <= 0.5 and >= -0.5)	81.5 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS Improved (<-0.5)	9.2 Percentage of Participants	—

PRIMARY outcome

Timeframe: Year 4

Outcome measures

Outcome measures
Measure	Ocrelizumab n=562 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS Worsened (>0.5)	18.0 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS Stable (Change <= 0.5 and >= -0.5)	59.3 Percentage of Participants	—
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS Improved (<-0.5)	22.8 Percentage of Participants	—

PRIMARY outcome

Timeframe: From Baseline to Week 24

Outcome measures

Outcome measures
Measure	Ocrelizumab n=671 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 24	-0.14 Change in Total EDSS Score Standard Deviation 0.68	—

PRIMARY outcome

Timeframe: From Baseline to Week 48

Outcome measures

Outcome measures
Measure	Ocrelizumab n=659 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 48	-0.14 Change in Total EDSS Score Standard Deviation 0.77	—

PRIMARY outcome

Timeframe: From Baseline to Week 72

Outcome measures

Outcome measures
Measure	Ocrelizumab n=651 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 72	-0.09 Change in Total EDSS Score Standard Deviation 0.89	—

PRIMARY outcome

Timeframe: Baseline, Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=637 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 96	-0.12 Change in Total EDSS Score Standard Error 0.95	—

PRIMARY outcome

Timeframe: Baseline, Week 120

Outcome measures

Outcome measures
Measure	Ocrelizumab n=579 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 120	-0.10 Change in Total EDSS Score Standard Deviation 0.94	—

PRIMARY outcome

Timeframe: Baseline, Week 144

Outcome measures

Outcome measures
Measure	Ocrelizumab n=561 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 144	-0.10 Change in Total EDSS Score Standard Error 1.00	—

PRIMARY outcome

Timeframe: Baseline, Week 168

Outcome measures

Outcome measures
Measure	Ocrelizumab n=560 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 168	-0.05 Change in Total EDSS Score Standard Error 1.05	—

PRIMARY outcome

Timeframe: Baseline, Week 192

Outcome measures

Outcome measures
Measure	Ocrelizumab n=562 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Mean Change From Baseline in EDSS Score at Week 192	-0.06 Change in Total EDSS Score Standard Deviation 1.06	—

PRIMARY outcome

Timeframe: Baseline up to 4 years

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.

Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 72	83.94 Percentage of participants Interval 80.92 to 86.52	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 96	80.38 Percentage of participants Interval 77.14 to 83.21	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 120	77.38 Percentage of participants Interval 73.99 to 80.39	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 144	75.76 Percentage of participants Interval 72.28 to 78.86	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 192	70.67 Percentage of participants Interval 66.97 to 74.04	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 24	95.98 Percentage of participants Interval 94.2 to 97.23	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 48	88.94 Percentage of participants Interval 86.3 to 91.09	—
Percentage of Participants Without Protocol-Defined Event of Disease Activity Week 168	72.79 Percentage of participants Interval 69.18 to 76.05	—

PRIMARY outcome

Timeframe: Baseline up to 4 years

Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Without Relapse Week 24	98.52 Percentage of Participants Interval 97.26 to 99.2	—
Percentage of Participants Without Relapse Week 48	97.91 Percentage of Participants Interval 96.5 to 98.76	—
Percentage of Participants Without Relapse Week 144	93.09 Percentage of Participants Interval 90.85 to 94.79	—
Percentage of Participants Without Relapse Week 72	96.25 Percentage of Participants Interval 94.49 to 97.45	—
Percentage of Participants Without Relapse Week 96	95.32 Percentage of Participants Interval 93.41 to 96.69	—
Percentage of Participants Without Relapse Week 120	93.90 Percentage of Participants Interval 91.78 to 95.49	—
Percentage of Participants Without Relapse Week 168	92.43 Percentage of Participants Interval 90.1 to 94.23	—
Percentage of Participants Without Relapse Week 192	91.56 Percentage of Participants Interval 89.12 to 93.48	—

PRIMARY outcome

Timeframe: Baseline up to 4 years

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.

Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is: Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable. The report contains data up to week 192 of the treatment period of each individual participant.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Annualized Relapse Rate	0.02 events per participant per year Interval 0.015 to 0.027	—

PRIMARY outcome

Timeframe: Week 24 through Week 144

Population: ITT Population included all randomized participants in shorter infusion sub study.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=373 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion n=372 Participants Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy	101 Participants	107 Participants

SECONDARY outcome

Timeframe: Week 192

Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=624 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Who Are Relapse Free	92.00 Percentage of Participants Interval 89.7 to 94.0	—

SECONDARY outcome

Timeframe: Weeks 96, 144, 192

Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan. Event-free rate

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With No Evidence of Protocol Defined Disease Activity Week 144	75.76 Percentage of Participants Interval 72.28 to 78.86	—
Percentage of Participants With No Evidence of Protocol Defined Disease Activity Week 192	70.67 Percentage of Participants Interval 66.97 to 74.04	—
Percentage of Participants With No Evidence of Protocol Defined Disease Activity Week 96	80.38 Percentage of Participants Interval 77.14 to 83.21	—

SECONDARY outcome

Timeframe: Weeks 96, 192

NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent \[%\] increase from baseline in timed 25 Foot Walk Test \[T25FWT\]; 20% increase from baseline in timed 9 hole peg test \[9HPT\]). CDP will be assessed using EDSS.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP) Week 96	79.60 Percentage of Participants Interval 76.33 to 82.48	—
Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP) Week 192	69.16 Percentage of Participants Interval 65.4 to 72.6	—

SECONDARY outcome

Timeframe: Weeks 96, 192

NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) Week 96	70.29 Percentage of Participants Interval 66.65 to 73.62	—
Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) Week 192	58.89 Percentage of Participants Interval 54.96 to 62.6	—

SECONDARY outcome

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

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint. As raw composite scores have been reported here, it is not possible to provide a score range for this scale.

MSFC combines the following: Timed 25 Foot Walk Test \[T25FWT\] for leg function \&ambulation measured in seconds (sec). The longer it takes to walk, higher the score indicating deterioration; 9 Hole Peg Test \[9HPT\] for arm \& handf unction measured in sec. Higher score=more time taken to complete test indicating deterioration. Paced Auditory Serial Addition Test \[PASAT\] for cognitive function (score range: 0-60, higher score=better cognitive processing speed). MSFC composite={\[Average(1/9-HPT)-Baseline Mean(1/9-HPT)/Baseline Std Dev(1/9-HPT)\]+\[-(Average T25FWT-Baseline Mean T25FWT)/Baseline Std-Dev T25FWT\]+\[(PASAT-3-BaselineMean PASAT-3)/Baseline Std Dev PASAT-3\]}/ 3.0. MSFC is based on the concept that scores for these 3 dimensions are combined to create a single score to detect change over time in a group of MS patients. Higher composite score=better overall function. Lower score=worse overall function. Higher mean change in total MSFC score=functional improvement at cohort level.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 24	0.09 score on a scale Standard Deviation 0.67	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 48	0.11 score on a scale Standard Deviation 0.54	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 72	0.12 score on a scale Standard Deviation 0.45	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 96	0.14 score on a scale Standard Deviation 0.53	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 120	0.16 score on a scale Standard Deviation 0.61	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 144	0.16 score on a scale Standard Deviation 0.48	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 168	0.18 score on a scale Standard Deviation 0.56	—
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total Change at Week 192	0.19 score on a scale Standard Deviation 0.72	—

SECONDARY outcome

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

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.

The change in the mean score of T25FW is reported below. The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. Higher times indicate worse performance and greater impairment. Subsequently, the lower the mean change in the score over time, the better performance.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 24	-0.31 seconds Standard Deviation 6.62	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 48	-0.49 seconds Standard Deviation 6.88	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 96	-0.62 seconds Standard Deviation 6.95	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 120	-0.44 seconds Standard Deviation 7.94	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 144	-0.97 seconds Standard Deviation 6.25	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 168	-0.83 seconds Standard Deviation 6.64	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 72	-0.56 seconds Standard Deviation 6.99	—
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. Change at Week 192	0.09 seconds Standard Deviation 9.37	—

SECONDARY outcome

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

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.

The mean change in 9 Hole Peg Test (9HPT)-score is reported. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. The number of seconds it takes to complete the test, the higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 48	-1.22 seconds Standard Deviation 11.54	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 72	-1.78 seconds Standard Deviation 8.09	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 96	-1.67 seconds Standard Deviation 10.91	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 120	-0.87 seconds Standard Deviation 15.21	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 144	-1.91 seconds Standard Deviation 8.70	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 168	-1.84 seconds Standard Deviation 10.68	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 192	-0.73 seconds Standard Deviation 17.55	—
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score Change at Week 24	-0.47 seconds Standard Deviation 14.44	—

SECONDARY outcome

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

Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.

Mean change in the Paced Auditory Serial Addition Test \[PASAT\] score is reported. PASAT measures cognitive function. A total of 60 single digit numbers are presented by an audiotape/CD-rom at a constant rate in every 3 seconds (PASAT-3). Participants are required to add each new number to the one immediately before it. Due to the relative complexity of this test, a practice trial with a set of 10 numbers should be performed before the original test. Participants are allowed up to 3 practice trials. Two sets of numbers (forms A \& B) are developed to be used alternatively in every visit to minimize memorizing. The number of correct answers is recorded. The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed. Subsequently, higher values in mean changes from baseline over the study time indicate improvement in cognitive function.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 24	4.18 score on a scale Standard Deviation 9.26	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 72	6.33 score on a scale Standard Deviation 11.59	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 96	7.66 score on a scale Standard Deviation 10.93	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 120	7.69 score on a scale Standard Deviation 12.95	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 144	8.45 score on a scale Standard Deviation 10.02	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 192	9.64 score on a scale Standard Deviation 11.56	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 48	5.40 score on a scale Standard Deviation 9.52	—
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score Change at Week 168	8.47 score on a scale Standard Deviation 11.79	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96, 144, 192

BICAMS is assessing cognitive processing speed and verbal and visual memory. SDMT assesses processing speed/working memory. 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 are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 second time span. The higher the results, the better processing speed/working memory.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=602 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) Change at Week 144	3.33 responses over 90 seconds Standard Deviation 9.31	—
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) Change at Week 192	4.38 responses over 90 seconds Standard Deviation 10.38	—
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) Change at Week 48	2.48 responses over 90 seconds Standard Deviation 10.12	—
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) Change at Week 96	1.89 responses over 90 seconds Standard Deviation 9.98	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96, 144, 192

BICAMS assesses cognitive processing speed and verbal and visual memory. The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. The maximum possible score is 80 and a minimum is 0. A higher score indicated better recall.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=130 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) Change at Week 48	2.02 score on a scale Standard Deviation 8.29	—
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) Change at Week 96	2.71 score on a scale Standard Deviation 9.25	—
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) Change at Week 144	3.99 score on a scale Standard Deviation 7.60	—
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) Change at Week 192	4.28 score on a scale Standard Deviation 13.76	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96, 144, 192

BICAMS assesses cognitive processing speed and verbal and visual memory. BVMT-R assesses visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=643 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) Baseline	23.69 points on a scale Standard Deviation 6.44	—
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) Change at Week 48	-0.71 points on a scale Standard Deviation 5.31	—
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) Change at Week 96	0.82 points on a scale Standard Deviation 5.68	—
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) Change at Week 192	1.06 points on a scale Standard Deviation 7.09	—
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) Change at Week 144	3.15 points on a scale Standard Deviation 5.37	—

SECONDARY outcome

Timeframe: Weeks 24, 48, 96, 144, 192

Population: ITT population

Number of Lesions are categorized as followed: 1, 2, 3, \>1, \>3

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 24 Number of Lesions 0	659 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 24 Number of Lesions 1	6 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 24 Number of Lesions 2	2 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 24 Number of Lesions >1	2 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 48 Number of Lesions 0	650 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 48 Number of Lesions 1	7 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 96 Number of Lesions 0	629 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 96 Number of Lesions 1	1 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 144 Number of Lesions 0	567 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 144 Number of Lesions 1	1 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 144 Number of Lesions 3	1 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 144 Number of Lesions >1	1 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 192 Number of Lesions 0	545 Number of Lesions	—
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI Week 192 Number of Lesions 1	1 Number of Lesions	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48, 96, 144, 192

Population: ITT Population

Number of Lesions are categorized as followed: 1, 2, 3, \>1

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 96 Number of Lesions >1	1 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 144 Number of Lesions 0	564 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 144 Number of Lesions 1	6 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 144 Number of Lesions 2	1 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 144 Number of Lesions 3	1 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 144 Number of Lesions >1	2 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 192 Number of Lesions 0	546 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 192 Number of Lesions 1	4 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 192 Number of Lesions 2	1 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 192 Number of Lesions >1	1 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 24 Number of Lesions 0	651 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 24 Number of Lesions 1	13 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 24 Number of Lesions 2	3 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 24 Number of Lesions >1	3 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 48 Number of Lesions 0	644 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 48 Number of Lesions 1	11 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 48 Number of Lesions 2	3 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 48 Number of Lesions 3	2 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 48 Number of Lesions >1	5 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 96 Number of Lesions 0	624 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 96 Number of Lesions 1	8 Number of Lesions	—
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI Week 96 Number of Lesions 2	1 Number of Lesions	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96, 144, 192

Population: ITT Population

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI Week 48	-310.63 Micro Liter Standard Deviation 708.07	—
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI Week 96	-405.61 Micro Liter Standard Deviation 755.99	—
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI Week 144	-359.76 Micro Liter Standard Deviation 761.84	—
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI Week 192	-307.64 Micro Liter Standard Deviation 797.87	—

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24, 48, 96, 144, 192

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.

Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI was measured for its volumes.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Baseline Week 8 1	6 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 24 0	635 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 24 1	6 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Baseline Week 8 0	633 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 48 0	631 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 48 1	6 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 96 0	611 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 96 1	7 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 144 0	550 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 144 1	5 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 192 0	530 Number of Lesions	—
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI Week 192 1	5 Number of Lesions	—

SECONDARY outcome

Timeframe: From Baseline to Weeks 24, 48, 96, 144, 192

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.

Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Change From Baseline in Brain Volume as Detected by Brain MRI Week 24	-0.189 Percentage Change in Volume (cm3) Standard Deviation 0.564	—
Change From Baseline in Brain Volume as Detected by Brain MRI Week 48	-0.479 Percentage Change in Volume (cm3) Standard Deviation 0.733	—
Change From Baseline in Brain Volume as Detected by Brain MRI Week 96	-0.909 Percentage Change in Volume (cm3) Standard Deviation 0.930	—
Change From Baseline in Brain Volume as Detected by Brain MRI Week 144	-1.283 Percentage Change in Volume (cm3) Standard Deviation 1.156	—
Change From Baseline in Brain Volume as Detected by Brain MRI Week 192	-1.535 Percentage Change in Volume (cm3) Standard Deviation 1.311	—

SECONDARY outcome

Timeframe: Baseline up to 4 years

Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants Without Treatment Discontinuation Week 168	87.17 Percentage % Interval 84.41 to 89.47	—
Percentage of Participants Without Treatment Discontinuation Week 192	83.85 Percentage % Interval 80.85 to 86.42	—
Percentage of Participants Without Treatment Discontinuation Week 24	98.97 Percentage % Interval 97.85 to 99.51	—
Percentage of Participants Without Treatment Discontinuation Week 48	97.49 Percentage % Interval 96.0 to 98.45	—
Percentage of Participants Without Treatment Discontinuation Week 72	96.02 Percentage % Interval 94.25 to 97.25	—
Percentage of Participants Without Treatment Discontinuation Week 96	93.51 Percentage % Interval 91.38 to 95.13	—
Percentage of Participants Without Treatment Discontinuation Week 120	92.04 Percentage % Interval 89.73 to 93.84	—
Percentage of Participants Without Treatment Discontinuation Week 144	89.23 Percentage % Interval 86.65 to 91.34	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48, 96, 120, 144, 192

WPAI scale measures impact of health problems on work productivity and regular activities: Absenteeism (Work Time Missed) measuring % of work time missed due to health issues; Presenteeism:Calculated as the percentage of impairment while working due to health problems. Overall Work Impairment:Calculated by combining absenteeism and presenteeism using the formula:Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism This formula accounts for both the time missed and the reduced productivity while at work. Activity Impairment: Calculated as the percentage of impairment in regular activities outside of work. Range: Each component is scored as 0%-100%). Higher % indicate greater impairment and worse outcomes.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Baseline	26.33 WAPI Sub-Score Standard Deviation 31.84	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Week 24	17.65 WAPI Sub-Score Standard Deviation 25.04	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Week 48	18.83 WAPI Sub-Score Standard Deviation 25.92	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Week 96	16.46 WAPI Sub-Score Standard Deviation 23.10	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Week 144	16.78 WAPI Sub-Score Standard Deviation 23.85	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Work productivity Week 192	15.80 WAPI Sub-Score Standard Deviation 22.25	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Activity Impairment Baseline	23.23 WAPI Sub-Score Standard Deviation 24.79	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Activity Impairment Week 24	18.09 WAPI Sub-Score Standard Deviation 22.15	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Presenteeism Week 48	18.85 WAPI Sub-Score Standard Deviation 23.37	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Activity Impairment Week 96	17.79 WAPI Sub-Score Standard Deviation 22.92	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Activity Impairment Week 144	17.80 WAPI Sub-Score Standard Deviation 23.74	—
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score Activity Impairment Week 192	18.18 WAPI Sub-Score Standard Deviation 23.25	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48, 96, 144, 192

The SMSS consists of 12 items which are assessed on a seven-point Likert scale that ranges from 0 (not at all affected) to 6 (total limitation) \[7\]. The total score ranges from 0 to 72, with higher scores indicating more severe symptom endorsement.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
SymptoMScreen Composite Score Week 24	-0.1 Change in SymptoMScreen Composite Score Standard Deviation 0.9	—
SymptoMScreen Composite Score Week 48	-0.1 Change in SymptoMScreen Composite Score Standard Deviation 1.0	—
SymptoMScreen Composite Score Week 96	0.0 Change in SymptoMScreen Composite Score Standard Deviation 1.1	—
SymptoMScreen Composite Score Week 144	0.0 Change in SymptoMScreen Composite Score Standard Deviation 1.1	—
SymptoMScreen Composite Score Week 192	0.0 Change in SymptoMScreen Composite Score Standard Deviation 1.1	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24, 48, 96, 144, 192

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a questionnaire to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective, which includes 29 items self-reported measures associated with a physical scale and 9 items with a psychological scale. MSIS-29 scales are generated by summing items and it's ranging from 29-145'. The higher total MSIS-29 scores indicate a greater degree of disability. The mean change in MSIS-29 scores from baseline is reported. The decreasing values in the mean change from baseline indicate functional improvement from patients' perspective

Outcome measures

Outcome measures
Measure	Ocrelizumab n=678 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score Week 24	-2.43 Change in MSIS-29 Mean Score Standard Deviation 12.13	—
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score Week 48	-2.15 Change in MSIS-29 Mean Score Standard Deviation 13.04	—
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score Week 96	-1.26 Change in MSIS-29 Mean Score Standard Deviation 14.31	—
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score Week 144	-0.73 Change in MSIS-29 Mean Score Standard Deviation 14.83	—
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score Week 192	-0.63 Change in MSIS-29 Mean Score Standard Deviation 16.04	—

SECONDARY outcome

Timeframe: Baseline up to 4 years

Population: Safety and ITT populations

Outcome measures

Outcome measures
Measure	Ocrelizumab n=1225 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Adverse Events	95.8 Percentage of Participants	—
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events	15.0 Percentage of Participants	—

SECONDARY outcome

Timeframe: From Week 24 to Week 144

Population: ITT Population included all randomized participants in shorter infusion sub study. Number analyzed is the number of participants who received an infusion.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=373 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion n=372 Participants Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Substudy: Number of Participants With IRR Overall and by Dose at Randomization All Randomized Doses (Overall)	155 Participants	172 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 1st Randomized Dose	101 Participants	107 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 2nd Randomized Dose	84 Participants	96 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 3rd Randomized Dose	62 Participants	82 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 4th Randomized Dose	14 Participants	17 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 5th Randomized Dose	1 Participants	3 Participants
Substudy: Number of Participants With IRR Overall and by Dose at Randomization 6th Randomized Dose	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Week 24 to Week 144

Population: ITT Population included all randomized participants in shorter infusion sub study. Number analyzed is the number of participants with IRR.

The number of participants with IRRs by most extreme intensity were reported (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 =life-threatening, grade 5 = fatal). Multiple IRRs in one participant are counted only once at the most extreme (highest) intensity observed.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=373 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion n=372 Participants Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Substudy: Severity of IRRs Grade 1 (Mild)	88 Participants	92 Participants
Substudy: Severity of IRRs Grade 2 (Moderate)	66 Participants	76 Participants
Substudy: Severity of IRRs Grade 3 (Severe)	1 Participants	4 Participants
Substudy: Severity of IRRs Grade 4 (Life-Threatening)	0 Participants	0 Participants
Substudy: Severity of IRRs Grade 5 (Fatal)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Week 24 to Week 144

Population: ITT Population included all randomized participants in shorter infusion sub study. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with an infusion.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=373 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion n=372 Participants Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Substudy: Number of IRR Symptoms	471 symptoms	458 symptoms

SECONDARY outcome

Timeframe: From Week 24 to Week 144

Population: ITT Population included all randomized participants in shorter infusion sub study.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=373 Participants First Enrollment Cohort. Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period	Substudy - Shorter Infusion n=372 Participants Ocrelizumab was administered as 600 mg IV infused over approximately 2 hours and saline for remaining 1.5 hours, every 24 weeks throughout the treatment period.
Substudy: IRRs Leading to Treatment Discontinuation	0 symptoms	0 symptoms

Adverse Events

Ocrelizumab

Serious events: 184 serious events

Other events: 1110 other events

Deaths: 13 deaths

Substudy - Conventional Infusion

Serious events: 21 serious events

Other events: 251 other events

Deaths: 2 deaths

Substudy - Shorter Infusion

Serious events: 19 serious events

Other events: 276 other events

Deaths: 1 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