Trial Outcomes & Findings for A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT) (NCT NCT02861014)

Last Updated: 2022-01-27

Results Overview

A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: * A protocol-defined relapse (PDR) * 24-week CDP based on increase in EDSS while on treatment with ocrelizumab * A T1 Gd-enhanced lesion after Week 8 * A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

681 participants

Primary outcome timeframe

Week 96

Results posted on

2022-01-27

Participant Flow

One additional participant was initially enrolled in error and the information provided is based on the ITT population.

Participant milestones

Participant milestones
Measure	Ocrelizumab Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Primary Analysis STARTED	680
Primary Analysis COMPLETED	641
Primary Analysis NOT COMPLETED	39
Safety Follow-up STARTED	64
Safety Follow-up COMPLETED	14
Safety Follow-up NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocrelizumab Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Primary Analysis Adverse Event	7
Primary Analysis Death	1
Primary Analysis Lack of Efficacy	3
Primary Analysis Physician Decision	2
Primary Analysis Pregnancy	4
Primary Analysis Protocol Violation	2
Primary Analysis Study Terminated By Sponsor	3
Primary Analysis Withdrawal by Subject	14
Primary Analysis Commercial ocrelizumab	3
Safety Follow-up Adverse Event	1
Safety Follow-up Pregnancy	1
Safety Follow-up Withdrawal by Subject	9
Safety Follow-up Study terminated by sponsor	1
Safety Follow-up Physician Decision	1
Safety Follow-up Roll-over to a long term extension study	1
Safety Follow-up Commercial ocrelizumab	36

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Age, Continuous	34.2 Years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	436 Participants n=5 Participants
Sex: Female, Male Male	244 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	579 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	74 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	625 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 96

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=658 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period	74.8 Percentage of Participants Interval 71.3 to 78.0	—

SECONDARY outcome

Timeframe: Baseline up to 24 weeks

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=673 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period	87.1 Percentage of Participants Interval 84.3 to 89.5	—

SECONDARY outcome

Timeframe: Baseline up to 48 weeks

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=665 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period	82.6 Percentage of Participants Interval 79.5 to 85.4	—

SECONDARY outcome

Timeframe: Baseline up to 96 Weeks

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

The definition of a protocol-defined event of disease activity is the occurrence of at least one of the following while on treatment with ocrelizumab: * A protocol-defined relapse defined as: Symptoms must persist for \>24 hours and should not be attributable to confounding clinical factors; Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment * 24 weeks confirmed disability progression based on increases in EDSS while on treatment with ocrelizumab * A T1 Gd-enhanced lesion after Week 8 * A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Time to First Protocol-Defined Event of Disease Activity	NA Weeks Insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Baseline, Weeks: 24, 48, 72, 96

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) Baseline	2.09 Points on scale Standard Deviation 1.06	—
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) Week 24	-0.02 Points on scale Standard Deviation 0.64	—
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) Week 48	0.01 Points on scale Standard Deviation 0.82	—
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) Week 72	-0.03 Points on scale Standard Deviation 0.85	—
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) Week 96	-0.01 Points on scale Standard Deviation 0.85	—

SECONDARY outcome

Timeframe: Up to Week 96

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=640 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Absolute Change From Baseline in EDSS Category at Week 96 Worsened (>0.5)	13.4 Percentage of Participants	—
Absolute Change From Baseline in EDSS Category at Week 96 Stable (Change <= 0.5 and >= -0.5)	72.2 Percentage of Participants	—
Absolute Change From Baseline in EDSS Category at Week 96 Improved (<-0.5)	14.4 Percentage of Participants	—

SECONDARY outcome

Timeframe: Week 96

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=399 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96	17.3 Percentage of Participants	—

SECONDARY outcome

Timeframe: Week 96

Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Annualized Protocol-defined Relapse Rate at Week 96	0.030 Relapses per participant per year Interval 0.023 to 0.038	—

SECONDARY outcome

Timeframe: Baseline up to 96 Weeks

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Time to Onset of 24-week Confirmed Disability Progression	NA Weeks Insufficient number of participants with events.	—

SECONDARY outcome

Timeframe: Baseline up to 96 Weeks

Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.

A protocol-defined multiple sclerosis (MS) relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: * Symptoms must persist for \>24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) * Symptoms should be preceded by neurological stability for at least 30 days * Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment, consistent with an increase of at least: * ≥ 0.5 points on EDSS scale * or ≥ 2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual * or ≥ 1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Time to Onset of First Protocol-Defined Relapse	NA Weeks Insufficient number of participants with event.	—

SECONDARY outcome

Timeframe: Baseline up to 96 Weeks

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Time to Onset of First New and/or Enlarging T2 Lesion	NA Weeks Insufficient number of participants with event.	—

SECONDARY outcome

Timeframe: Weeks: 24, 48, 96

Mean number of T1 Gd-enhancing lesions per MRI scan: Total number of T1 Gd-enhanced lesions divided by the total number of interpretable MRI scans

Outcome measures

Outcome measures
Measure	Ocrelizumab n=665 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 Week 24	0.004 Lesions per scan Interval 0.001 to 0.014	—
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 Week 48	0.004 Lesions per scan Interval 0.001 to 0.011	—
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 Week 96	NA Lesions per scan No result could be obtained for Week 96, as the model did not converge.	—

SECONDARY outcome

Timeframe: Baseline, Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=632 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From	-558.6 mL Standard Deviation 1194.6	—

SECONDARY outcome

Timeframe: Baseline, Week 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=632 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI	-8.5 Percentage Change From Baseline Standard Deviation 18.2	—

SECONDARY outcome

Timeframe: Weeks 24, 48, 96

The number of new and/or enlarging T2 lesions at week 24, 48 and 96 is calculated as the sum of the individual number of new and/or enlarging lesions at each visit. Data from other unscheduled assessments is included in this summary or analysis.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=670 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 Week 24	21.4 uL Standard Deviation 241.7	—
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 Week 48	23.1 uL Standard Deviation 510.2	—
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 Week 96	3.7 uL Standard Deviation 41.6	—

SECONDARY outcome

Timeframe: Weeks 24, 48, 96

Mean number of new and/or enlarging T2 hyperintense lesions per MRI scan: Total number of new and/or enlarging T2 hyperintense lesions divided by the total number of interpretable MRI scans

Outcome measures

Outcome measures
Measure	Ocrelizumab n=671 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan Week 24	0.053 Lesions per scan Interval 0.038 to 0.075	—
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan Week 48	0.009 Lesions per scan Interval 0.004 to 0.017	—
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan Week 96	0.011 Lesions per scan Interval 0.006 to 0.02	—

SECONDARY outcome

Timeframe: Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=666 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 48	-416.5 mL Standard Deviation 1224.3	—
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 96	-528.5 mL Standard Deviation 1144.7	—

SECONDARY outcome

Timeframe: Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 48	-4.0 Percentage change from baseline Standard Deviation 149.7	—
Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 96	-12.5 Percentage change from baseline Standard Deviation 21.1	—

SECONDARY outcome

Timeframe: Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=666 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 48	-461.8 mL Interval -613.8 to -309.7	—
Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume Week 96	-576.5 mL Interval -727.0 to -426.1	—

SECONDARY outcome

Timeframe: Weeks 24, 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=538 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Adjusted Mean Percentage Change From Baseline in Brain Volume Week 24	-0.153 Mean percentage change from baseline Interval -0.259 to -0.047	—
Adjusted Mean Percentage Change From Baseline in Brain Volume Week 48	-0.445 Mean percentage change from baseline Interval -0.556 to -0.334	—
Adjusted Mean Percentage Change From Baseline in Brain Volume Week 96	-0.805 Mean percentage change from baseline Interval -0.94 to -0.669	—

SECONDARY outcome

Timeframe: Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=432 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume Week 48	-0.312 Mean percentage change from baseline Interval -0.606 to -0.019	—
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume Week 96	-0.618 Mean percentage change from baseline Interval -0.928 to -0.308	—

SECONDARY outcome

Timeframe: Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=432 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Adjusted Mean Percentage Change From Baseline in White Matter Volume Week 48	-0.382 Mean percentage change from baseline Interval -0.609 to -0.154	—
Adjusted Mean Percentage Change From Baseline in White Matter Volume Week 96	-0.745 Mean percentage change from baseline Interval -0.983 to -0.507	—

SECONDARY outcome

Timeframe: Baseline, Weeks: 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing 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 sec time span. The higher the results, the better processing speed/working memory.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=610 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score Baseline	53.8 Correct responses over 90 seconds Standard Deviation 13.0	—
Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score Week 48	2.5 Correct responses over 90 seconds Standard Deviation 9.8	—
Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score Week 96	1.3 Correct responses over 90 seconds Standard Deviation 10.2	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96

Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing 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=599 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score Baseline	25.0 Points on scale Standard Deviation 6.3	—
Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score Week 48	-1.9 Points on scale Standard Deviation 5.3	—
Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score Week 96	-1.5 Points on scale Standard Deviation 5.4	—

SECONDARY outcome

Timeframe: Baseline, Weeks 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=610 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score Week 48	7.2 Percentage change from baseline Standard Deviation 30.8	—
Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score Week 96	4.8 Percentage change from baseline Standard Deviation 30.6	—

SECONDARY outcome

Timeframe: Baseline, Weeks: 48, 96

Outcome measures

Outcome measures
Measure	Ocrelizumab n=599 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score Week 48	-4.4 Percentage change from baseline Standard Deviation 31.1	—
Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score Week 96	-2.0 Percentage change from baseline Standard Deviation 33.7	—

SECONDARY outcome

Timeframe: Baseline up to to 96 weeks after the end of the Treatment Period

Population: Safety analyses were done on the ITT population.

Outcome measures

Outcome measures
Measure	Ocrelizumab n=680 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up n=64 Participants Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	89.1 Percentage of Participants	57.8 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAE	7.2 Percentage of Participants	9.4 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Deaths	0.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs leading to study drug discontinuation	1.0 Percentage of Participants	NA Percentage of Participants During Safety follow-up period participants didn't receive study drug anymore
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs leading to study drug discontinuation	0.7 Percentage of Participants	NA Percentage of Participants During Safety follow-up period participants didn't receive study drug anymore
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs leading to dose modification/interruptionb	15.0 Percentage of Participants	NA Percentage of Participants During Safety follow-up period participants didn't receive study drug anymore
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Infusion-related reactions (IRRs)	43.2 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious IRRs	0.1 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Infections	66.9 Percentage of Participants	28.1 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious infections	1.6 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Malignancies	0.4 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Pregnancies	0.7 Percentage of Participants	1.5 Percentage of Participants

Adverse Events

Ocrelizumab

Serious events: 49 serious events

Other events: 531 other events

Deaths: 1 deaths

Ocrelizumab Safety Follow-up

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Ocrelizumab n=680 participants at risk Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Ocrelizumab Safety Follow-up n=64 participants at risk Participants received Ocrelizumab as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Infections and infestations NASOPHARYNGITIS	30.9% 210/680 • Number of events 449 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	17.2% 11/64 • Number of events 19 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Respiratory, thoracic and mediastinal disorders COUGH	6.9% 47/680 • Number of events 56 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	6.2% 4/64 • Number of events 4 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Gastrointestinal disorders DIARRHOEA	6.2% 42/680 • Number of events 52 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Gastrointestinal disorders NAUSEA	5.6% 38/680 • Number of events 40 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
General disorders FATIGUE	9.9% 67/680 • Number of events 106 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
General disorders PYREXIA	6.9% 47/680 • Number of events 62 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Infections and infestations INFLUENZA	13.5% 92/680 • Number of events 137 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Infections and infestations ORAL HERPES	8.1% 55/680 • Number of events 116 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Infections and infestations SINUSITIS	5.3% 36/680 • Number of events 58 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	7.5% 51/680 • Number of events 81 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Infections and infestations URINARY TRACT INFECTION	10.3% 70/680 • Number of events 108 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Injury, poisoning and procedural complications INFUSION RELATED REACTION	43.2% 294/680 • Number of events 569 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Musculoskeletal and connective tissue disorders ARTHRALGIA	5.4% 37/680 • Number of events 40 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	6.9% 47/680 • Number of events 58 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Nervous system disorders HEADACHE	22.6% 154/680 • Number of events 320 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Nervous system disorders PARAESTHESIA	5.0% 34/680 • Number of events 43 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Psychiatric disorders INSOMNIA	5.0% 34/680 • Number of events 43 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	6.2% 42/680 • Number of events 55 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.
Musculoskeletal and connective tissue disorders BACK PAIN	8.4% 57/680 • Number of events 74 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.	0.00% 0/64 • From Baseline up to to 96 weeks after the end of the Treatment Period. Time frame includes the safety-follow-up period. One participant discontinued the study before receiving treatment and was excluded from safety population.