A Study of Ocrelizumab in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Are Naive to Methotrexate (FILM)

Sponsor
Genentech, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT00485589
Collaborator
Roche Pharma AG (Industry)
613
3
74.6

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of ocrelizumab, compared with placebo, in combination with methotrexate in patients with active rheumatoid arthritis who are naive to methotrexate. Patients will be randomized to receive placebo, ocrelizumab 200mg i.v. or ocrelizumab 500mg i.v. on Days 1 and 15. Repeat courses of i.v. treatment will be administered at weeks 24, 52 and 76. All patients will receive concomitant methotrexate (7.5 mg escalating to 20mg p.o. weekly). The anticipated time on study treatment is 2+ years, and the target sample size is 500+ individuals.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
613 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Parallel Group, International Study to Evaluate the Safety and Efficacy of Ocrelizumab in Combination With Methotrexate (MTX) Compared to MTX Alone in Methotrexate- Naive Patients With Active Rheumatoid Arthritis
Actual Study Start Date :
Jun 11, 2007
Actual Primary Completion Date :
Jan 29, 2010
Actual Study Completion Date :
Aug 29, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Placebo
Intravenous repeating dose

Experimental: Ocrelizumab 200 mg

Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Methotrexate
Oral repeating dose

Drug: Ocrelizumab
Intravenous repeating dose

Experimental: Ocrelizumab 500 mg

Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.

Drug: Methotrexate
Oral repeating dose

Drug: Ocrelizumab
Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

  1. Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52 [Baseline to Week 52]

    The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.

Secondary Outcome Measures

  1. Percentage of Participants Without Radiographic Progression (RP) at Week 52 [Week 52]

    RP was defined as a change from Baseline in the modified Total Sharp Score (mTSS) ≤ 0. The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.

  2. Percentage of Participants With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52 [Baseline to Week 52]

    Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "none" [symptom-free and no arthritis symptoms] and the extreme right end "maximum" [maximum arthritis disease activity]; patient assessment of pain in the previous 24 hours on a VAS (extreme left end of the line "none" and the extreme right end "unbearable"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.

  3. Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52 [Week 24 and Week 52]

    A participant was in DAS28 remission if their DAS28 score < 2.6). The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score indicates more disease activity.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
  • Age ≥ 18

  • Rheumatoid arthritis for 3 months-5 years

  • Naive to methotrexate

  • If receiving steroids or NSAIDs, must be on a stable dose for 4 weeks prior to baseline

Exclusion criteria:
  • Rheumatic autoimmune disease or inflammatory joint disease other than RA

  • Prior receipt of any biologic therapy for RA

  • Concurrent treatment with any DMARD

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Genentech, Inc.
  • Roche Pharma AG

Investigators

  • Study Director: Wolfgang Dummer, M.D., Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00485589
Other Study ID Numbers:
  • ACT3984g
  • WA20497
First Posted:
Jun 13, 2007
Last Update Posted:
Nov 3, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Genentech, Inc.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail The study population comprised adult patients with active rheumatoid arthritis (RA) of at least 3 months' but less than 5 years' duration who were naïve to methotrexate. Additionally, patients were required to be naïve to any biologic therapy for RA prior to enrollment.
Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.
Period Title: Overall Study
STARTED 210 200 203
COMPLETED 183 180 185
NOT COMPLETED 27 20 18

Baseline Characteristics

Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg Total
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Total of all reporting groups
Overall Participants 207 196 202 605
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
49.2
(12.43)
50.8
(13.17)
48.6
(12.29)
49.5
(12.66)
Sex/Gender, Customized (Number) [Number]
Female
153
73.9%
154
78.6%
161
79.7%
468
77.4%
Male
54
26.1%
42
21.4%
41
20.3%
137
22.6%

Outcome Measures

1. Primary Outcome
Title Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 52
Description The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
Time Frame Baseline to Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.
Measure Participants 193 187 194
Mean (Standard Deviation) [Units on a scale]
1.59
(4.815)
0.66
(4.509)
0.27
(2.908)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 200 mg
Comments
Type of Statistical Test Non-Inferiority
Comments Pre-specified analysis
Statistical Test of Hypothesis p-Value 0.001
Comments
Method Van Elteren's test
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 500 mg
Comments
Type of Statistical Test Non-Inferiority
Comments Pre-specified analysis
Statistical Test of Hypothesis p-Value 0.0033
Comments
Method Van Elteren's test
Comments
2. Secondary Outcome
Title Percentage of Participants Without Radiographic Progression (RP) at Week 52
Description RP was defined as a change from Baseline in the modified Total Sharp Score (mTSS) ≤ 0. The mTSS is a measure of joint damage and includes measures of joint erosion (JE) and joint space narrowing (JSN). The JE score, using the van der Heijde modification, measures erosion severity in 32 hand joints and 12 foot joints. Each hand joint is scored from 0 to 5 and each foot joint is scored from 0 to 10; the total score ranges from 0 to 280. Each joint is scored according to the surface area involved. A score of 10 indicates extensive loss of bone from more than one-half of the articulating bone; a score of 0 indicates no erosion. The JSN score measures the severity of JSN in 30 hand joints (15 per hand) and 12 foot joints (6 per foot). Each joint is scored from 0 to 4; the total score ranges from 0 to 168. A higher score indicates more joint space narrowing. The mTSS ranges from 0 to 448 (280+168). A higher mTSS score indicates greater damage. A negative change score indicates improvement.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.
Measure Participants 196 187 192
Number (95% Confidence Interval) [Percentage of participants]
51
24.6%
66.3
33.8%
68.8
34.1%
3. Secondary Outcome
Title Percentage of Participants With an Improvement ≥ 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline to Week 52
Description Improvement must be seen in tender (68) and swollen (66) joint counts. Joints were assessed and classified as swollen/not swollen and tender/not tender by pressure and joint manipulation. Improvement must also be seen in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "none" [symptom-free and no arthritis symptoms] and the extreme right end "maximum" [maximum arthritis disease activity]; patient assessment of pain in the previous 24 hours on a VAS (extreme left end of the line "none" and the extreme right end "unbearable"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C-reactive protein (CRP), or erythrocyte sedimentation rate if CRP was missing.
Time Frame Baseline to Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.
Measure Participants 207 196 200
ACR20
57.5
27.8%
73
37.2%
71
35.1%
ACR50
39.6
19.1%
60.7
31%
54.5
27%
ACR70
20.3
9.8%
38.3
19.5%
38
18.8%
4. Secondary Outcome
Title Percentage of Participants in Disease Activity Score 28 (DAS28) Remission at Weeks 24 and 52
Description A participant was in DAS28 remission if their DAS28 score < 2.6). The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where a higher score indicates more disease activity.
Time Frame Week 24 and Week 52

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Ocrelizumab 200 mg Ocrelizumab 500 mg
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, and 76. Participants also received methotrexate 7.5 mg orally weekly starting on Day 1. The dose of methodrexate was increased to a dose of 20 mg per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone or prednisolone.
Measure Participants 207 196 200
Week 24
9.7
4.7%
19.9
10.2%
18
8.9%
Week 52
7.2
3.5%
27
13.8%
28
13.9%

Adverse Events

Time Frame Baseline up to 30 months.
Adverse Event Reporting Description Safety population: All randomized participants who received at least 1 dose of study medication.
Arm/Group Title Placebo - Treatment Period Placebo/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 200 mg - Treatment Period Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period Placebo - Safety Follow-up Period Placebo/Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 200 mg - Safety Follow-up Period Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period
Arm/Group Description Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received placebo intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, and 78 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received Ocrelizumab intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76. Participants received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received ocrelizumab 200 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54 and 76 and ocrelizumab 500 mg intravenously on Weeks 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76 and 78. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone. Participants had received ocrelizumab 500 mg intravenously on Days 1 and 15 and Weeks 24, 26, 52, 54, 76, 100, 102, 124, and 126. Participants also received methotrexate 20 mg orally per week by Week 8, administered in 1 dose or divided into 3 equal doses administered at 12-hour intervals. Participants also received acetaminophen 1 g and an antihistamine (diphenhydramine HCl 50 mg or equivalent dose of an alternative) orally 30-60 minutes prior to each infusion of study treatment and methylprednisolone 100 mg intravenously 30 minutes prior to each infusion of study treatment. Participants also received folate ≥ 5 mg/week either as a single dose or as a divided weekly dose. Participants were also allowed to continue receiving background corticosteroid therapy, at a dose of ≤ 10 mg/day of prednisolone.
All Cause Mortality
Placebo - Treatment Period Placebo/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 200 mg - Treatment Period Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period Placebo - Safety Follow-up Period Placebo/Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 200 mg - Safety Follow-up Period Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/207 (0%) 0/10 (0%) 0/196 (0%) 0/12 (0%) 0/202 (0%) 0/6 (0%) 2/187 (1.1%) 0/9 (0%) 2/177 (1.1%) 0/11 (0%) 1/185 (0.5%) 0/6 (0%)
Serious Adverse Events
Placebo - Treatment Period Placebo/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 200 mg - Treatment Period Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period Placebo - Safety Follow-up Period Placebo/Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 200 mg - Safety Follow-up Period Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 22/207 (10.6%) 0/10 (0%) 21/196 (10.7%) 1/12 (8.3%) 31/202 (15.3%) 0/6 (0%) 11/187 (5.9%) 2/9 (22.2%) 2/177 (1.1%) 0/11 (0%) 4/185 (2.2%) 0/6 (0%)
Blood and lymphatic system disorders
Agranulocytosis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Anaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Anaemia haemolytic autoimmune 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Neutropenia 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Leukopenia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Pancytopenia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Cardiac disorders
Acute myocardial infarction 1/207 (0.5%) 1 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Coronary artery disease 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Arteriosclerosis coronary artery 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Atrial fibrillation 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Tachycardia 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Supraventricular tachycardia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Congenital, familial and genetic disorders
Bronchogenic cyst 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Ear and labyrinth disorders
Deafness bilateral 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Vestibular disorder 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Endocrine disorders
Hyperthyroidism 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Eye disorders
Cataract 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastrointestinal disorders
Inguinal hernia 2/207 (1%) 2 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Abdominal hernia obstructive 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Constipation 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastritis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastrointestinal haemorrhage 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastrointestinal inflammation 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Intestinal obstruction 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Colitis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Upper gastrointestinal haemorrhage 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
General disorders
Non-cardiac chest pain 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pyrexia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Hepatobiliary disorders
Cholelithiasis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 2/202 (1%) 2 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Hepatic cirrhosis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Infections and infestations
Urinary tract infection 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 2/202 (1%) 4 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Abdominal wall infection 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 1/12 (8.3%) 1 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Abscess 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Acute tonsillitis 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Bacteraemia 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Bronchitis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Bronchopneumonia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Cellulitis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Diverticulitis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 1
Encephalitis viral 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Histoplasmosis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Infection 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Localised infection 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pneumonia herpes viral 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Systemic candida 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Sepsis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Oesophageal candidiasis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Peritonitis bacterial 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pharyngitis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Post procedural infection 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Urosepsis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Pneumonia 3/207 (1.4%) 3 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 2/202 (1%) 2 0/6 (0%) 0 1/187 (0.5%) 1 1/9 (11.1%) 1 2/177 (1.1%) 2 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Injury, poisoning and procedural complications
Road traffic accident 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Accidental overdose 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Dislocation of vertebra 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Forearm fracture 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Hip fracture 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Infusion related reaction 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Limb traumatic amputation 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Upper limb fracture 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Joint dislocation 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Lower limb fracture 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Subdural haematoma 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Metabolism and nutrition disorders
Hyperglycaemia 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Diabetes mellitus 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Hypoglycaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis 2/207 (1%) 2 0/10 (0%) 0 2/196 (1%) 2 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 2/177 (1.1%) 2 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Osteoarthritis 0/207 (0%) 0 0/10 (0%) 0 2/196 (1%) 2 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Back pain 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Osteonecrosis 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Colon cancer metastatic 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Prostate cancer 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Ovarian fibroma 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Nervous system disorders
Autonomic neuropathy 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 11 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Carpal tunnel syndrome 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Cerebellar infarction 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Cerebrovascular accident 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Leukoencephalopathy 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Dementia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Ischaemic cerebral infarction 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Psychiatric disorders
Depression 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Renal and urinary disorders
Nephrolithiasis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Renal failure 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 3/202 (1.5%) 3 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pulmonary alveolar haemorrhage 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pulmonary eosinophilia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Vocal cord polyp 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Asthma 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Chronic obstructive pulmonary disease 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Pustular psoriasis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Angioedema 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Vascular disorders
Aortic aneurysm 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Aortic stenosis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Deep vein thrombosis 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Orthostatic hypotension 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo - Treatment Period Placebo/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 200 mg - Treatment Period Ocrelizumab 200 mg/Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg - Treatment Period Ocrelizumab 500 mg/Ocrelizumab 500 mg - Treatment Period Placebo - Safety Follow-up Period Placebo/Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 200 mg - Safety Follow-up Period Ocrelizumab 200 mg/Ocrelizumab 500 Mg-safety Follow-up Period Ocrelizumab 500 mg - Safety Follow-up Period Ocrelizumab 500 mg/Ocrelizumab 500 mg -Safety Follow-up Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 128/207 (61.8%) 4/10 (40%) 135/196 (68.9%) 6/12 (50%) 144/202 (71.3%) 3/6 (50%) 35/187 (18.7%) 3/9 (33.3%) 32/177 (18.1%) 3/11 (27.3%) 49/185 (26.5%) 5/6 (83.3%)
Blood and lymphatic system disorders
Lymphadenopathy 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Neutropenia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Anaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 3/177 (1.7%) 3 0/11 (0%) 0 2/185 (1.1%) 3 0/6 (0%) 0
Eye disorders
Conjunctivitis 0/207 (0%) 0 1/10 (10%) 1 0/196 (0%) 0 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastrointestinal disorders
Abdominal hernia 1/207 (0.5%) 1 0/10 (0%) 0 0/196 (0%) 0 1/12 (8.3%) 1 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Nausea 24/207 (11.6%) 24 0/10 (0%) 0 16/196 (8.2%) 16 0/12 (0%) 0 22/202 (10.9%) 22 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Diarrhoea 14/207 (6.8%) 14 0/10 (0%) 0 7/196 (3.6%) 7 0/12 (0%) 0 14/202 (6.9%) 14 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 3/177 (1.7%) 3 1/11 (9.1%) 1 3/185 (1.6%) 3 0/6 (0%) 0
Dyspepsia 14/207 (6.8%) 14 0/10 (0%) 0 8/196 (4.1%) 8 0/12 (0%) 0 13/202 (6.4%) 13 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Abdominal distension 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastric ulcer 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
Gastritis atrophic 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
General disorders
Oedema 2/207 (1%) 2 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 1/6 (16.7%) 1 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Hepatobiliary disorders
Drug-induced liver injury 18/207 (8.7%) 18 0/10 (0%) 0 28/196 (14.3%) 28 0/12 (0%) 0 27/202 (13.4%) 27 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Infections and infestations
Upper respiratory tract infection 36/207 (17.4%) 45 0/10 (0%) 0 31/196 (15.8%) 38 0/12 (0%) 0 23/202 (11.4%) 29 1/6 (16.7%) 1 7/187 (3.7%) 7 1/9 (11.1%) 1 3/177 (1.7%) 3 2/11 (18.2%) 3 7/185 (3.8%) 7 0/6 (0%) 0
Cystitis 3/207 (1.4%) 4 0/10 (0%) 0 4/196 (2%) 6 0/12 (0%) 0 4/202 (2%) 4 1/6 (16.7%) 1 1/187 (0.5%) 1 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Tooth infection 1/207 (0.5%) 1 1/10 (10%) 1 1/196 (0.5%) 1 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Bronchitis 21/207 (10.1%) 21 0/10 (0%) 0 22/196 (11.2%) 22 0/12 (0%) 0 15/202 (7.4%) 15 0/6 (0%) 0 3/187 (1.6%) 3 1/9 (11.1%) 1 5/177 (2.8%) 5 0/11 (0%) 0 3/185 (1.6%) 5 0/6 (0%) 0
Urinary tract infection 12/207 (5.8%) 12 0/10 (0%) 0 21/196 (10.7%) 21 0/12 (0%) 0 25/202 (12.4%) 25 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 5/177 (2.8%) 5 0/11 (0%) 0 12/185 (6.5%) 12 0/6 (0%) 0
Nasopharyngitis 11/207 (5.3%) 11 0/10 (0%) 0 18/196 (9.2%) 18 0/12 (0%) 0 16/202 (7.9%) 16 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Sinusitis 10/207 (4.8%) 10 0/10 (0%) 0 7/196 (3.6%) 7 0/12 (0%) 0 15/202 (7.4%) 15 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Gastroenteritis 9/207 (4.3%) 9 0/10 (0%) 0 10/196 (5.1%) 10 0/12 (0%) 0 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Cellulitis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Influenza 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 2/187 (1.1%) 2 1/9 (11.1%) 1 1/177 (0.6%) 1 1/11 (9.1%) 1 3/185 (1.6%) 4 0/6 (0%) 0
Tinea versicolour 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 2/185 (1.1%) 2 0/6 (0%) 0
Fungal skin infection 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Lower respiratory tract infection 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Sinusitis bacterial 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Injury, poisoning and procedural complications
Infusion related reaction 21/207 (10.1%) 36 4/10 (40%) 4 56/196 (28.6%) 79 0/12 (0%) 0 64/202 (31.7%) 91 1/6 (16.7%) 1 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Meniscus injury 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 2/187 (1.1%) 2 0/9 (0%) 0 1/177 (0.6%) 1 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
Limb injury 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
Muscle strain 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Foot fracture 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
Investigations
Liver function test abnormal 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 1/12 (8.3%) 1 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Blood creatine phosphokinase increased 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 1/177 (0.6%) 1 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Metabolism and nutrition disorders
Hyperlipidaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Vitamin D deficiency 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 1/6 (16.7%) 1
Dyslipidaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 1/177 (0.6%) 1 0/11 (0%) 0 1/185 (0.5%) 1 1/6 (16.7%) 1
Hypocalcaemia 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Musculoskeletal and connective tissue disorders
Periarthritis 0/207 (0%) 0 0/10 (0%) 0 1/196 (0.5%) 1 1/12 (8.3%) 1 1/202 (0.5%) 1 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Back pain 9/207 (4.3%) 9 0/10 (0%) 0 10/196 (5.1%) 10 0/12 (0%) 0 7/202 (3.5%) 7 0/6 (0%) 0 4/187 (2.1%) 4 1/9 (11.1%) 1 2/177 (1.1%) 2 0/11 (0%) 0 6/185 (3.2%) 7 0/6 (0%) 0
Osteoarthritis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 1/177 (0.6%) 1 1/11 (9.1%) 1 2/185 (1.1%) 2 0/6 (0%) 0
Tenosynovitis stenosans 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Nervous system disorders
Headache 13/207 (6.3%) 13 0/10 (0%) 0 12/196 (6.1%) 12 0/12 (0%) 0 7/202 (3.5%) 7 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Psychiatric disorders
Anxiety 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Respiratory, thoracic and mediastinal disorders
Wheezing 0/207 (0%) 0 1/10 (10%) 1 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Cough 0/207 (0%) 0/10 (0%) 0/196 (0%) 0/12 (0%) 0/202 (0%) 0/6 (0%) 2/187 (1.1%) 2 1/9 (11.1%) 1 2/177 (1.1%) 2 0/11 (0%) 0 1/185 (0.5%) 1 0/6 (0%) 0
Sinusitis noninfective 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 1/6 (16.7%) 1
Skin and subcutaneous tissue disorders
Dry skin 2/207 (1%) 3 0/10 (0%) 0 1/196 (0.5%) 1 1/12 (8.3%) 1 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Erythema 0/207 (0%) 0 1/10 (10%) 1 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Rosacea 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 1/12 (8.3%) 1 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Exfoliative rash 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Rash 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 1/187 (0.5%) 1 0/9 (0%) 0 2/177 (1.1%) 2 1/11 (9.1%) 1 1/185 (0.5%) 1 0/6 (0%) 0
Dermatitis contact 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 2/187 (1.1%) 2 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 1/6 (16.7%) 1
Angioedema 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Onychoclasis 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 1/11 (9.1%) 1 0/185 (0%) 0 0/6 (0%) 0
Pruritus 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 1/9 (11.1%) 1 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Surgical and medical procedures
Hip arthroplasty 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 1/12 (8.3%) 2 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0
Bunion operation 0/207 (0%) 0 0/10 (0%) 0 0/196 (0%) 0 0/12 (0%) 0 0/202 (0%) 0 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 1/6 (16.7%) 1
Vascular disorders
Hypertension 23/207 (11.1%) 23 0/10 (0%) 0 14/196 (7.1%) 14 0/12 (0%) 0 18/202 (8.9%) 18 0/6 (0%) 0 0/187 (0%) 0 0/9 (0%) 0 0/177 (0%) 0 0/11 (0%) 0 0/185 (0%) 0 0/6 (0%) 0

Limitations/Caveats

The study was terminated prematurely by the sponsors before all patients could reach the time point for primary analysis at Week 104. No patient received any further infusions of study medication.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title Medical Communications
Organization F. Hoffmann-La Roche AG
Phone 41 616878333
Email global.trial_information@roche.com
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00485589
Other Study ID Numbers:
  • ACT3984g
  • WA20497
First Posted:
Jun 13, 2007
Last Update Posted:
Nov 3, 2020
Last Verified:
Oct 1, 2020