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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01412333
Recruitment Status : Completed
First Posted : August 9, 2011
Results First Posted : July 18, 2017
Last Update Posted : March 8, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing Multiple Sclerosis
Interventions Drug: Interferon beta-1a
Drug: Ocrelizumab-matching placebo
Drug: Ocrelizumab
Drug: Interferon beta-1a-matching placebo
Enrollment 835
Recruitment Details A total of 1045 participants were screened for entry into the study. Of these, 210 participants failed screening; the main reasons were failure to meet the inclusion/exclusion criteria or unacceptable laboratory values. A total of 835 participants were enrolled in the study.
Pre-assignment Details All participants were provided an opportunity to rollover and continue treatment and/or safety follow-up under the new extension protocol MN43964. In error, the study completion status for 5 participants was registered as 'Sponsor Termination' in the study eCRF. All 5 participants opted not to be enrolled into MN43964 and decided to pursue treatment outside the context of a clinical trial. In conclusion, the 5 participants should be considered as having completed the WA21093 study.
Arm/Group Title Interferon Beta-1a + Ocrelizumab Placebo Ocrelizumab + Interferon Beta-1a Placebo
Hide Arm/Group Description Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Period Title: Overall Study
Started 418 417
Entered OLE Period 297 350
Completed 229 225
Not Completed 189 192
Reason Not Completed
Adverse Event             40             42
Death             5             6
Lack of Efficacy             22             10
Lost to Follow-up             15             12
Non-Compliance             3             7
Non-Compliance With Study Drug             1             1
Other             30             33
Physician Decision             11             16
Pregnancy             6             4
Protocol Violation             1             2
Study Terminated By Sponsor             3             2
Withdrawal by Subject             51             54
Missing             1             3
Arm/Group Title Interferon Beta-1a + Ocrelizumab Placebo (Double Blind Period) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind Period) Total
Hide Arm/Group Description Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week. Total of all reporting groups
Overall Number of Baseline Participants 418 417 835
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 418 participants 417 participants 835 participants
37.4  (9.0) 37.2  (9.1) 37.3  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 418 participants 417 participants 835 participants
Female
280
  67.0%
271
  65.0%
551
  66.0%
Male
138
  33.0%
146
  35.0%
284
  34.0%
1.Primary Outcome
Title Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks In Double Blind Period
Hide Description ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses/participant year of treatment
0.290
(0.234 to 0.361)
0.155
(0.121 to 0.198)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments Adjusted by Geographical Region (US vs. Rest of World) and baseline EDSS (<4.0 vs. >=4.0).
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.532
Confidence Interval (2-Sided) 95%
0.397 to 0.714
Estimation Comments Rate ratio was calculated as Ocrelizumab ARR/Interferon beta-1a 44 mcg SC ARR.
2.Secondary Outcome
Title Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period
Hide Description Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Time Frame Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Median (Full Range)
Unit of Measure: weeks
NA [1] 
(0 to 102)
NA [2] 
(0 to 104)
[1]
Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.
[2]
Median of time to onset of CDP was not achieved due to low number of participants with events. The lower-limit value is a censored observation.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments Time to onset of CDP at week 12
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0169
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.42 to 0.92
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment
Hide Description The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.
Time Frame Baseline up to week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Measure Type: Number
Unit of Measure: lesions
465 21
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.051
Confidence Interval 95%
0.029 to 0.089
Estimation Comments Adjusted by baseline T1 Gd lesion (present or not), baseline EDSS (<4.0 vs. >=4.0) and geographical region (US vs. rest-of-world). Adjusted rate ratio was calculated as Ocrelizumab adjusted rate/Interferon beta-1a 44 mcg SC adjusted rate.
4.Secondary Outcome
Title Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment
Hide Description The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.
Time Frame Baseline up to week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Measure Type: Number
Unit of Measure: lesions
2103 380
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.171
Confidence Interval 95%
0.130 to 0.225
Estimation Comments Adjusted by baseline T2 lesion count, baseline EDSS (<4.0 vs. >=4.0) and geographical region (US vs. rest-of-world). Adjusted rate ratio was calculated as Ocrelizumab adjusted rate/Interferon beta-1a 44 mcg SC adjusted rate.
5.Secondary Outcome
Title Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks In Double Blind Period
Hide Description Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of >= 2.0. It was defined as a reduction in EDSS score of: A) >=1.0 from the baseline EDSS score when the baseline score was >=2 and <=5.5 B) >= 0.5 when the baseline EDSS score > 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study. Here, number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 308 318
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.83
(14.62 to 23.65)
21.38
(17.01 to 26.30)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.4019
Comments [Not Specified]
Method CMH Chi-Squared test (stratified)
Comments Stratified by Geographical Region (US vs. Rest of World) and baseline EDSS (<4.0 vs. >=4.0).
Method of Estimation Estimation Parameter Relative risk (stratified)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.84 to 1.56
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period
Hide Description Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Time Frame Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Median (Full Range)
Unit of Measure: weeks
NA [1] 
(0 to 102)
NA [1] 
(0 to 104)
[1]
Median of time to onset of CDP was not achieved due to low number of participants with events. The full-range values are censored observations.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments Time to onset of CDP at week 24
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.037
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.40 to 0.98
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of T1 Hypointense Lesions During the Double-Blind Treatment
Hide Description The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96.
Time Frame Baseline up to week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Measure Type: Number
Unit of Measure: lesions
1484 567
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted rate ratio
Estimated Value 0.357
Confidence Interval 95%
0.272 to 0.47
Estimation Comments Adjusted by baseline T1-hypointense lesion count, baseline EDSS (<4.0 vs. >=4.0) and geographical region (US vs. rest-of-world). Adjusted rate ratio was calculated as Ocrelizumab adjusted rate/Interferon beta-1a 44 mcg SC adjusted rate.
8.Secondary Outcome
Title Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 In Double Blind Period
Hide Description MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study. Here, n signifies the number of participants evaluable at specified time points.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Mean (Standard Error)
Unit of Measure: Z-score
Unadjusted Baseline mean (n= 342, 358) -0.001  (0.033) 0.026  (0.034)
Adjusted Week 96 mean (n= 269, 308) 0.169  (0.029) 0.276  (0.028)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.004
Comments [Not Specified]
Method mixed-effect model of repeated measures
Comments Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix.
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.107
Confidence Interval (2-Sided) 95%
0.034 to 0.180
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.037
Estimation Comments Difference in adjusted means was calculated as Ocrelizumab adjusted mean at Week 96/ Interferon beta-1a 44 mcg SC adjusted mean at Week 96.
9.Secondary Outcome
Title Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 In Double Blind Period
Hide Description Brain volume was recorded as an absolute "normalized" value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + ([percentage change in brain volume from baseline visit to Week 24]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (< 4.0 vs. >= 4.0) + Week + Treatment + Treatment*Week (repeated values over Week) + Brain Volume at Week 24*Week. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis).
Time Frame From week 24 up to week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study. Here, number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 259 287
Mean (Standard Error)
Unit of Measure: percent change
-0.75  (0.051) -0.638  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.09
Comments [Not Specified]
Method mixed-effect model of repeated measures
Comments Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix.
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.112
Confidence Interval (2-Sided) 95%
-0.018 to 0.241
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.066
Estimation Comments Difference in the rate of brain volume loss: 14.9%. Difference in adjusted means was calculated as Ocrelizumab adjusted mean at Week 96/ Interferon beta-1a 44 mcg SC adjusted mean at Week 96.
10.Secondary Outcome
Title Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 In Double Blind Period
Hide Description The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t- scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.
Time Frame Baseline, Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Descriptive statistics at baseline include participants with assessment at baseline and at least one post- baseline value. ITT population included all randomized participants in the study. Here, n signifies the number of participants evaluable at specified time points.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 418 417
Mean (Standard Error)
Unit of Measure: t-score
Unadjusted Baseline mean (n= 319, 355) 44.552  (0.544) 44.307  (0.541)
Adjusted mean change at week 96(n=276, 315) -0.833  (0.472) 0.326  (0.444)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0404
Comments [Not Specified]
Method mixed-effect model of repeated measures
Comments Estimates are from analysis based on mixed-effect model of repeated measures using unstructured covariance matrix.
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 1.159
Confidence Interval (2-Sided) 95%
0.051 to 2.268
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.564
Estimation Comments Difference in adjusted means was calculated as Ocrelizumab adjusted mean at Week 96/ Interferon beta-1a 44 mcg SC adjusted mean at Week 96.
11.Secondary Outcome
Title Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 In Double Blind Period
Hide Description NEDA was defined only for participants with a baseline EDSS score >=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants in the study. Here, number of participants analysed signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 270 289
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.1
(19.1 to 29.6)
43.9
(38.1 to 49.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method CMH Chi-Squared test (stratified)
Comments Analyzed using CMH test, stratified by Geographical Region (US vs. rest-of-world) and baseline EDSS (<4.0 vs. >=4.0).
Method of Estimation Estimation Parameter Relative risk (stratified)
Estimated Value 1.81
Confidence Interval (2-Sided) 95%
1.41 to 2.32
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received any study drug.
Arm/Group Title Interferon Beta-1a + Ocrelizumab Placebo (Double Blind Period) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind Period) Interferon Beta-1a + Placebo (Open Label Extension) Ocrelizumab + Placebo (Open Label Extension)
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
Overall Number of Participants Analyzed 417 417 297 350
Measure Type: Number
Unit of Measure: participants
Adverse Events 357 360 281 333
Serious Adverse Events 40 29 71 121
13.Secondary Outcome
Title Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) In Double Blind Period
Hide Description AUC represents total drug exposure for one dosing interval after the 4th dose.
Time Frame Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetics (PK) population included all participants in the ocrelizumab group who had at least 1 measurable concentration value.
Arm/Group Title Ocrelizumab
Hide Arm/Group Description:
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 389
Mean (Standard Deviation)
Unit of Measure: micrograms per milliter*day
3513  (955)
14.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab In Double Blind Period
Hide Description Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period.
Time Frame Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline evaluable participants with an ADA assay result from a baseline sample(s). The safety population included all participants who received any study drug. Here, n signifies the number of participants evaluable at the specified time points.
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab
Hide Arm/Group Description:
Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.
Overall Number of Participants Analyzed 417 417
Measure Type: Number
Unit of Measure: participants
Positive sample at baseline (n= 407, 402) 2 4
Positive for ADA post-baseline (n= 403, 405) 5 2
Time Frame Baseline to approximately 588 weeks
Adverse Event Reporting Description The safety population included all participants who received any study drug.
 
Arm/Group Title Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab (Open Label) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Ocrelizumab (Open Label)
Hide Arm/Group Description Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week. In DB phase participants received Interferon Beta-1a and Ocrelizumab Placebo. During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks. In DB phase participants received Ocrelizumab + Interferon Beta-1a Placebo. During the OLE phase, all participants received ocrelizumab 600-mg IV infusion every 24 weeks.
All-Cause Mortality
Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab (Open Label) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Ocrelizumab (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/417 (0.24%)      1/417 (0.24%)      5/297 (1.68%)      6/350 (1.71%)    
Hide Serious Adverse Events
Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab (Open Label) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Ocrelizumab (Open Label)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/417 (9.59%)      29/417 (6.95%)      71/297 (23.91%)      121/350 (34.57%)    
Blood and lymphatic system disorders         
ANAEMIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
FEBRILE NEUTROPENIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
NEUTROPENIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
SPLENIC INFARCTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
SPLENIC VEIN THROMBOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
SPONTANEOUS HAEMATOMA † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
Cardiac disorders         
ACUTE MYOCARDIAL INFARCTION † 1  1/417 (0.24%)  1 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
ANGINA UNSTABLE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
MYOCARDIAL INFARCTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  2
SUPRAVENTRICULAR TACHYCARDIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Congenital, familial and genetic disorders         
TRISOMY 21 † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Endocrine disorders         
GOITRE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
THYROIDITIS SUBACUTE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Eye disorders         
CATARACT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
RETINAL DETACHMENT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Gastrointestinal disorders         
ABDOMINAL PAIN † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
APPENDICITIS NONINFECTIVE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
COLITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
CROHN'S DISEASE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
DIVERTICULUM † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ENTEROVESICAL FISTULA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
GASTRITIS † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
GASTROINTESTINAL INFLAMMATION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
ILEUS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ILEUS PARALYTIC † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
INGUINAL HERNIA † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MECHANICAL ILEUS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
OESOPHAGITIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
PANCREATITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
PANCREATITIS ACUTE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
RECTAL HAEMORRHAGE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SMALL INTESTINAL OBSTRUCTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
UMBILICAL HERNIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
General disorders         
CHEST PAIN † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
DEATH † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
PYREXIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 3/350 (0.86%)  3
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Hepatobiliary disorders         
BILE DUCT STENOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
CHOLECYSTITIS † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 1/297 (0.34%)  1 3/350 (0.86%)  3
CHOLECYSTITIS ACUTE † 1  1/417 (0.24%)  1 1/417 (0.24%)  1 1/297 (0.34%)  1 2/350 (0.57%)  2
CHOLELITHIASIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HEPATITIS ACUTE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
HEPATITIS FULMINANT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
LIVER DISORDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Immune system disorders         
HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Infections and infestations         
ABDOMINAL ABSCESS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ACUTE HEPATITIS C † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
ACUTE SINUSITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  2
ANAL ABSCESS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
APPENDICITIS † 1  0/417 (0.00%)  0 3/417 (0.72%)  3 0/297 (0.00%)  0 1/350 (0.29%)  1
ATYPICAL PNEUMONIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
BRONCHITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
CELLULITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
CELLULITIS PHARYNGEAL † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
CHOLECYSTITIS INFECTIVE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
CHRONIC SINUSITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
COVID-19 † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 9/297 (3.03%)  9 13/350 (3.71%)  13
COVID-19 PNEUMONIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 13/297 (4.38%)  13 23/350 (6.57%)  24
CYSTITIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ENCEPHALITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
ENTEROCOCCAL INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ENTEROVIRUS INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
FURUNCLE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
GASTRITIS VIRAL † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
GASTROENTERITIS VIRAL † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HERPES ZOSTER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
INJECTION SITE CELLULITIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
LYME DISEASE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MASTOIDITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MENINGITIS ASEPTIC † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MENINGITIS VIRAL † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
NEUTROPENIC SEPSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ORCHITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
OTITIS MEDIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PARASITIC GASTROENTERITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PASTEURELLA INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
PELVIC INFLAMMATORY DISEASE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
PERIRECTAL ABSCESS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PHARYNGITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
PNEUMOCOCCAL SEPSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PNEUMONIA † 1  2/417 (0.48%)  2 1/417 (0.24%)  1 6/297 (2.02%)  7 15/350 (4.29%)  15
PNEUMONIA ASPIRATION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 1/297 (0.34%)  1 0/350 (0.00%)  0
PNEUMONIA BACTERIAL † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
PNEUMONIA HAEMOPHILUS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PNEUMONIA VIRAL † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
POSTOPERATIVE WOUND INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 2/297 (0.67%)  4 0/350 (0.00%)  0
PYELONEPHRITIS † 1  0/417 (0.00%)  0 2/417 (0.48%)  2 1/297 (0.34%)  1 1/350 (0.29%)  1
PYELONEPHRITIS ACUTE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
PYURIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SEPSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
SEPTIC SHOCK † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SKIN INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
STAPHYLOCOCCAL INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
STAPHYLOCOCCAL SEPSIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
TOOTH INFECTION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
URINARY TRACT INFECTION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 4/297 (1.35%)  5 3/350 (0.86%)  3
UROSEPSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
VASCULAR DEVICE INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
VIRAL INFECTION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
VIRAL PERICARDITIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
VIRAL SEPSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Injury, poisoning and procedural complications         
ACETABULUM FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ALCOHOL POISONING † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
ANASTOMOTIC LEAK † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ANKLE FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
BRAIN CONTUSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
CARTILAGE INJURY † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
CLAVICLE FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
EPICONDYLITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
FEMUR FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
FIBULA FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
FRACTURE DISPLACEMENT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HAND FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HIP FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
INCISIONAL HERNIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
INFUSION RELATED REACTION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  2 0/350 (0.00%)  0
JAW FRACTURE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
JOINT DISLOCATION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
JOINT INJURY † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
LOWER LIMB FRACTURE † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
LUMBAR VERTEBRAL FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MENISCUS INJURY † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 2/350 (0.57%)  2
MULTIPLE INJURIES † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
POST PROCEDURAL HAEMATOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SKULL FRACTURE † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
SPINAL CORD INJURY CAUDA EQUINA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SUBDURAL HAEMATOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
TIBIA FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
TOXICITY TO VARIOUS AGENTS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
TRAUMATIC INTRACRANIAL HAEMORRHAGE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
UPPER LIMB FRACTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Investigations         
HEPATIC ENZYME INCREASED † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Metabolism and nutrition disorders         
DECREASED APPETITE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
DEHYDRATION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
GOUT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HYPERTRIGLYCERIDAEMIA † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
HYPOGLYCAEMIA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
HYPOKALAEMIA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 1/350 (0.29%)  1
HYPOPROTEINAEMIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
IMPAIRED INSULIN SECRETION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Musculoskeletal and connective tissue disorders         
ARTHRITIS † 1  0/417 (0.00%)  0 1/417 (0.24%)  2 0/297 (0.00%)  0 0/350 (0.00%)  0
BACK PAIN † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
INTERVERTEBRAL DISC DISORDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
INTERVERTEBRAL DISC PROTRUSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  4 1/350 (0.29%)  1
OSTEOARTHRITIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
SYNOVIAL CYST † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
VERTEBRAL OSTEOPHYTE † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
BLADDER CANCER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
BREAST CANCER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 2/297 (0.67%)  2 0/350 (0.00%)  0
CHONDROSARCOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
FIBROADENOMA OF BREAST † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
INTRADUCTAL PROLIFERATIVE BREAST LESION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
LEIOMYOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MALIGNANT MELANOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
METASTATIC MALIGNANT MELANOMA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
OVARIAN GERM CELL TERATOMA BENIGN † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PROSTATE CANCER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
TESTIS CANCER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
THYROID ADENOMA † 1  0/417 (0.00%)  0 2/417 (0.48%)  2 0/297 (0.00%)  0 0/350 (0.00%)  0
TUMOUR HAEMORRHAGE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
TUMOUR RUPTURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
UTERINE LEIOMYOMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Nervous system disorders         
CAROTID ARTERY STENOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
CEREBRAL INFARCTION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
CEREBROVASCULAR ACCIDENT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
COGNITIVE DISORDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
DIZZINESS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
EPILEPSY † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
FACIAL PARALYSIS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
HEAD DISCOMFORT † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
HYDROCEPHALUS † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
ISCHAEMIC STROKE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
LUMBOSACRAL RADICULOPATHY † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MULTIPLE SCLEROSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
MULTIPLE SCLEROSIS PSEUDO RELAPSE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MULTIPLE SCLEROSIS RELAPSE † 1  2/417 (0.48%)  2 1/417 (0.24%)  1 2/297 (0.67%)  2 2/350 (0.57%)  2
NEUROLOGICAL SYMPTOM † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
OPTIC NEURITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PRESYNCOPE † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
RADICULOPATHY † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
SEIZURE † 1  1/417 (0.24%)  1 2/417 (0.48%)  2 0/297 (0.00%)  0 1/350 (0.29%)  1
SPINAL CORD COMPRESSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
TRIGEMINAL NEURALGIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Pregnancy, puerperium and perinatal conditions         
ABORTION SPONTANEOUS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 2/297 (0.67%)  2 0/350 (0.00%)  0
BREECH PRESENTATION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Psychiatric disorders         
ANXIETY † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
APATHY † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
COMPLETED SUICIDE † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 1/350 (0.29%)  1
CONVERSION DISORDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
DEPRESSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  2
DEPRESSION SUICIDAL † 1  2/417 (0.48%)  2 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
DEPRESSIVE DELUSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MAJOR DEPRESSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
MENTAL STATUS CHANGES † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  2 0/350 (0.00%)  0
PSYCHOTIC DISORDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
STRESS † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
SUICIDAL IDEATION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 2/350 (0.57%)  2
SUICIDE ATTEMPT † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 2/297 (0.67%)  2 0/350 (0.00%)  0
Renal and urinary disorders         
ACUTE KIDNEY INJURY † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
CALCULUS BLADDER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
NEPHRITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
NEPHROLITHIASIS † 1  2/417 (0.48%)  2 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
URETHRAL CYST † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Reproductive system and breast disorders         
ADENOMYOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
COITAL BLEEDING † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
DYSMENORRHOEA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
ENDOMETRIOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
HEAVY MENSTRUAL BLEEDING † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
MENOMETRORRHAGIA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
OVARIAN CYST † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  1 1/350 (0.29%)  1
UTERINE POLYP † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
ACUTE RESPIRATORY FAILURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
ASTHMA † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 1/350 (0.29%)  1
HYPERSENSITIVITY PNEUMONITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
LARYNGEAL OEDEMA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PARANASAL SINUS INFLAMMATION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PULMONARY EMBOLISM † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 3/350 (0.86%)  3
PULMONARY INFARCTION † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 0/297 (0.00%)  0 0/350 (0.00%)  0
RESPIRATORY FAILURE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
TONSILLAR INFLAMMATION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
TRACHEAL STENOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Skin and subcutaneous tissue disorders         
DRUG ERUPTION † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
Surgical and medical procedures         
STERILISATION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
Vascular disorders         
DEEP VEIN THROMBOSIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 0/297 (0.00%)  0 1/350 (0.29%)  1
PERIPHERAL VENOUS DISEASE † 1  0/417 (0.00%)  0 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
VARICOSE VEIN † 1  1/417 (0.24%)  1 0/417 (0.00%)  0 1/297 (0.34%)  1 0/350 (0.00%)  0
1
Term from vocabulary, MedDRA 25.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Interferon Beta-1a + Ocrelizumab Placebo (Double Blind) Ocrelizumab (Open Label) Ocrelizumab + Interferon Beta-1a Placebo (Double Blind) Ocrelizumab (Open Label)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   357/417 (85.61%)      360/417 (86.33%)      266/297 (89.56%)      317/350 (90.57%)    
Gastrointestinal disorders         
CONSTIPATION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 13/297 (4.38%)  15 20/350 (5.71%)  22
DIARRHOEA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 19/297 (6.40%)  32 30/350 (8.57%)  37
NAUSEA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 17/297 (5.72%)  25 22/350 (6.29%)  25
General disorders         
FATIGUE † 1  39/417 (9.35%)  52 44/417 (10.55%)  57 39/297 (13.13%)  55 50/350 (14.29%)  70
INFLUENZA LIKE ILLNESS † 1  92/417 (22.06%)  106 23/417 (5.52%)  25 15/297 (5.05%)  17 26/350 (7.43%)  28
PYREXIA † 1  25/417 (6.00%)  34 15/417 (3.60%)  18 20/297 (6.73%)  22 34/350 (9.71%)  53
INJECTION SITE ERYTHEMA † 1  55/417 (13.19%)  59 1/417 (0.24%)  1 0/297 (0.00%)  0 0/350 (0.00%)  0
INJECTION SITE REACTION † 1  28/417 (6.71%)  28 2/417 (0.48%)  2 0/297 (0.00%)  0 0/350 (0.00%)  0
Infections and infestations         
BRONCHITIS † 1  13/417 (3.12%)  15 22/417 (5.28%)  28 25/297 (8.42%)  33 57/350 (16.29%)  85
INFLUENZA † 1  20/417 (4.80%)  25 24/417 (5.76%)  30 38/297 (12.79%)  54 55/350 (15.71%)  66
NASOPHARYNGITIS † 1  41/417 (9.83%)  60 80/417 (19.18%)  128 65/297 (21.89%)  120 96/350 (27.43%)  327
SINUSITIS † 1  20/417 (4.80%)  25 27/417 (6.47%)  35 34/297 (11.45%)  46 47/350 (13.43%)  84
UPPER RESPIRATORY TRACT INFECTION † 1  53/417 (12.71%)  89 65/417 (15.59%)  109 86/297 (28.96%)  267 107/350 (30.57%)  325
URINARY TRACT INFECTION † 1  39/417 (9.35%)  48 43/417 (10.31%)  74 79/297 (26.60%)  212 96/350 (27.43%)  257
COVID-19 † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 66/297 (22.22%)  79 96/350 (27.43%)  120
CYSTITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 15/297 (5.05%)  26 21/350 (6.00%)  37
GASTROENTERITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 15/297 (5.05%)  17 24/350 (6.86%)  28
HERPES ZOSTER † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 7/297 (2.36%)  7 21/350 (6.00%)  28
ORAL HERPES † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 10/297 (3.37%)  16 21/350 (6.00%)  50
PNEUMONIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 11/297 (3.70%)  11 23/350 (6.57%)  28
RESPIRATORY TRACT INFECTION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 16/297 (5.39%)  20 25/350 (7.14%)  41
RHINITIS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 6/297 (2.02%)  7 18/350 (5.14%)  19
Injury, poisoning and procedural complications         
INFUSION RELATED REACTION † 1  50/417 (11.99%)  64 158/417 (37.89%)  271 97/297 (32.66%)  177 63/350 (18.00%)  168
CONTUSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 15/297 (5.05%)  15 15/350 (4.29%)  21
LIGAMENT SPRAIN † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 18/297 (6.06%)  19 23/350 (6.57%)  27
Musculoskeletal and connective tissue disorders         
ARTHRALGIA † 1  27/417 (6.47%)  33 22/417 (5.28%)  28 44/297 (14.81%)  57 53/350 (15.14%)  68
BACK PAIN † 1  18/417 (4.32%)  19 28/417 (6.71%)  31 44/297 (14.81%)  65 48/350 (13.71%)  61
MYALGIA † 1  27/417 (6.47%)  30 12/417 (2.88%)  13 17/297 (5.72%)  29 15/350 (4.29%)  16
MUSCLE SPASMS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 14/297 (4.71%)  20 20/350 (5.71%)  25
MUSCULAR WEAKNESS † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 15/297 (5.05%)  28 19/350 (5.43%)  27
NECK PAIN † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 15/297 (5.05%)  16 16/350 (4.57%)  20
PAIN IN EXTREMITY † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 33/297 (11.11%)  60 42/350 (12.00%)  60
Nervous system disorders         
HEADACHE † 1  71/417 (17.03%)  106 60/417 (14.39%)  88 49/297 (16.50%)  73 68/350 (19.43%)  95
HYPOAESTHESIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 21/297 (7.07%)  41 24/350 (6.86%)  38
MULTIPLE SCLEROSIS RELAPSE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 70/297 (23.57%)  150 82/350 (23.43%)  157
PARAESTHESIA † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 21/297 (7.07%)  27 26/350 (7.43%)  39
DIZZINESS † 1  23/417 (5.52%)  27 17/417 (4.08%)  19 0/297 (0.00%)  0 0/350 (0.00%)  0
MIGRAINE † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 9/297 (3.03%)  19 20/350 (5.71%)  29
Psychiatric disorders         
DEPRESSION † 1  31/417 (7.43%)  34 29/417 (6.95%)  32 35/297 (11.78%)  40 38/350 (10.86%)  45
INSOMNIA † 1  23/417 (5.52%)  24 23/417 (5.52%)  28 22/297 (7.41%)  25 21/350 (6.00%)  26
Respiratory, thoracic and mediastinal disorders         
COUGH † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 26/297 (8.75%)  43 58/350 (16.57%)  89
OROPHARYNGEAL PAIN † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 17/297 (5.72%)  22 21/350 (6.00%)  25
Skin and subcutaneous tissue disorders         
RASH † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 23/297 (7.74%)  28 25/350 (7.14%)  30
Vascular disorders         
HYPERTENSION † 1  0/417 (0.00%)  0 0/417 (0.00%)  0 14/297 (4.71%)  15 26/350 (7.43%)  27
1
Term from vocabulary, MedDRA 25.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01412333    
Other Study ID Numbers: WA21093
2010-020315-36 ( EudraCT Number )
First Submitted: August 8, 2011
First Posted: August 9, 2011
Results First Submitted: March 30, 2017
Results First Posted: July 18, 2017
Last Update Posted: March 8, 2024