Trial Outcomes & Findings for A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis (NCT NCT01247324)

Last Updated: 2024-03-04

Results Overview

ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

821 participants

Primary outcome timeframe

Week 96

Results posted on

2024-03-04

Participant Flow

1051 participants were screened for entry into study. 821 participants were entered into double-blind treatment period. Participants who completed the 96-week double-blind treatment had option to enter a single group, active treatment open label extension, providing they fulfilled the eligibility criteria and at study completion date, all participants are provided opportunity to rollover and continue treatment and/or safety follow-up under new extension protocol MN43964 (NCT05269004).

In error, the study completion status for 5 participants in WA21092 was registered as 'Sponsor Termination' in the study eCRF. However, all 5 participants were successfully enrolled into MN43964 and thus have completed the WA21092 study.

Participant milestones

Participant milestones
Measure	Interferon Beta-1a 44 mcg SC Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Study STARTED	411	410
Overall Study Entered Open-Label Extension	326	352
Overall Study COMPLETED	226	239
Overall Study NOT COMPLETED	185	171

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon Beta-1a 44 mcg SC Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Study Death	6	10
Overall Study Physician Decision	2	3
Overall Study Non-compliance with study drug	3	0
Overall Study Lack of Efficacy	24	14
Overall Study Non-compliance	3	2
Overall Study Pregnancy	5	10
Overall Study Protocol Violation	1	1
Overall Study Reason not specified	42	32
Overall Study Consent withdrawn by participant	41	56
Overall Study Adverse Event	49	35
Overall Study Lost to Follow-up	3	6
Overall Study Study Terminated by Sponsor	4	1
Overall Study Missing	2	1

Baseline Characteristics

A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Total n=821 Participants Total of all reporting groups
Age, Continuous	36.9 years STANDARD_DEVIATION 9.3 • n=5 Participants	37.1 years STANDARD_DEVIATION 9.3 • n=7 Participants	37.0 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	272 Participants n=5 Participants	270 Participants n=7 Participants	542 Participants n=5 Participants
Sex: Female, Male Male	139 Participants n=5 Participants	140 Participants n=7 Participants	279 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 96

Population: Intent-to-treat (ITT) population included all randomized participants in the study.

ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks	0.292 relapses/participant year of treatment Interval 0.235 to 0.361	0.156 relapses/participant year of treatment Interval 0.122 to 0.2	—	—

SECONDARY outcome

Timeframe: Week 108

Population: ITT population included all randomized participants in the study.

Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period	NA weeks Interval 0.0 to 103.0 Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.	NA weeks Interval 0.0 to 108.0 Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 96

Population: ITT population included all randomized participants in the study.

The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment	337 lesions	21 lesions	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 96

Population: ITT population included all randomized participants in the study.

The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment	1916 lesions	430 lesions	—	—

SECONDARY outcome

Timeframe: Week 96

Population: ITT population included all randomized participants in the study. Here, number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of \>= 2.0. It was defined as a reduction in EDSS score of: A) \>=1.0 from the baseline EDSS score when the baseline score was \>=2 and \<=5.5 B) \>= 0.5 when the baseline EDSS score \> 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=306 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=310 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks	12.42 percentage of participants Interval 8.94 to 16.64	20.00 percentage of participants Interval 15.69 to 24.89	—	—

SECONDARY outcome

Timeframe: Week 108

Population: ITT population included all randomized participants in the study.

Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period	NA weeks Interval 0.0 to 103.0 Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.	NA weeks Interval 0.0 to 108.0 Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.	—	—

SECONDARY outcome

Timeframe: Baseline up to Week 96

Population: ITT population included all randomized participants in the study.

The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Number of T1 Hypointense Lesions During the Double-Blind Treatment	1307 lesions	564 lesions	—	—

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: ITT population included all randomized participants in the study. Here, n signifies the number of participants evaluable at specified time points.

MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 Unadjusted Baseline mean	0.028 Z-score Standard Error 0.034	-0.012 Z-score Standard Error 0.040	—	—
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 Adjusted Week 96 mean	0.174 Z-score Standard Error 0.031	0.213 Z-score Standard Error 0.031	—	—

SECONDARY outcome

Timeframe: From Week 24 up to Week 96

Population: ITT population included all randomized participants in the study. Here, number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Brain volume was recorded as an absolute "normalized" value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + (\[percentage change in brain volume from baseline visit to Week 24\]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (\< 4.0 vs. \>= 4.0) + Week + Treatment + Treatment\*Week (repeated values over Week) + Brain Volume at Week 24\*Week.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=267 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=281 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96	-0.741 percent change Standard Error 0.046	-0.572 percent change Standard Error 0.044	—	—

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: Descriptive statistics at baseline include participants with assessment at baseline and at least one post- baseline value. ITT population included all randomized participants in the study. Here, n signifies the number of participants evaluable at specified time points.

The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t- scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=411 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=410 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 Unadjusted Baseline mean	45.399 t-score Standard Error 0.529	45.065 t-score Standard Error 0.507	—	—
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 Adjusted mean change at week 96	-0.657 t-score Standard Error 0.475	0.036 t-score Standard Error 0.456	—	—

SECONDARY outcome

Timeframe: Week 96

Population: ITT population included all randomized participants in the study. Here, number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

NEDA was defined only for participants with a baseline EDSS score \>=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=291 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=289 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96	27.1 percentage of participants Interval 22.1 to 32.6	47.4 percentage of participants Interval 41.5 to 53.3	—	—

SECONDARY outcome

Timeframe: Baseline up to 588 weeks

Population: The safety population included all participants who received any study drug.

AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=409 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=408 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) n=326 Participants During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) n=352 Participants During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Number of Participants With Adverse Events (AEs)	331 Participants	327 Participants	302 Participants	319 Participants

SECONDARY outcome

Timeframe: Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96

Population: The pharmacokinetics (PK) population included all participants in the ocrelizumab group who had at least 1 measurable concentration value.

AUC represents total drug exposure for one dosing interval after the 4th dose.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=393 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC)	3513 micrograms per milliliter*day Standard Deviation 955	—	—	—

SECONDARY outcome

Timeframe: Baseline up to week 96

Population: Baseline evaluable participants with an ADA assay result from a baseline sample(s). The safety population included all participants who received any study drug. Here, n signifies the number of participants evaluable at the specified time points.

Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a 44 mcg SC n=409 Participants Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Ocrelizumab n=408 Participants Ocrelizumab 600 mg intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Interferon Beta-1a + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.	Ocrelizumab + Placebo (Open Label Extension) During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab Positive sample at baseline	2 Participants	1 Participants	—	—
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab Positive for ADA post-baseline	2 Participants	1 Participants	—	—

Adverse Events

Interferon Beta -1a + Placebo (Double Blind Period)

Serious events: 32 serious events

Other events: 257 other events

Deaths: 1 deaths

Ocrelizumab + Placebo (Double Blind Period)

Serious events: 28 serious events

Other events: 241 other events

Deaths: 0 deaths

Interferon Beta-1a + Placebo (Open Label Extension)

Serious events: 109 serious events

Other events: 285 other events

Deaths: 6 deaths

Ocrelizumab + Placebo (Open Label Extension)

Serious events: 116 serious events

Other events: 286 other events

Deaths: 11 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