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Trial record 30 of 647 for:    Russian Federation | Chile

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

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ClinicalTrials.gov Identifier: NCT01247324
Recruitment Status : Active, not recruiting
First Posted : November 24, 2010
Results First Posted : July 18, 2017
Last Update Posted : July 10, 2019
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 821
Recruitment Details  
Pre-assignment Details A total of 1051 participants were screened for entry into the study. 821 participants were entered into the double-blind treatment period. Participants who completed the 96-week double-blind treatment had an option to enter a single group, active treatment open label extension, providing they fulfilled the eligibility criteria.
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 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 411 410
Completed 340 366
Not Completed 71 44
Reason Not Completed
Death             1             0
Physician Decision             0             1
Non-compliance with study drug             3             0
Lack of Efficacy             12             8
Non-compliance             2             0
Pregnancy             2             3
Protocol Violation             1             2
Reason not specified             11             8
Consent withdrawn by participant             13             8
Adverse Event             25             13
Lost to Follow-up             1             1
Arm/Group Title Interferon Beta-1a 44 mcg SC Ocrelizumab 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 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 411 410 821
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 411 participants 410 participants 821 participants
36.9  (9.3) 37.1  (9.3) 37.0  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 411 participants 410 participants 821 participants
Female
272
  66.2%
270
  65.9%
542
  66.0%
Male
139
  33.8%
140
  34.1%
279
  34.0%
1.Primary Outcome
Title Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks
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 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 411 410
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses/participant year of treatment
0.292
(0.235 to 0.361)
0.156
(0.122 to 0.200)
Show Statistical Analysis 1 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
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 0.536
Confidence Interval (2-Sided) 95%
0.4 to 0.719
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. 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 108
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 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 411 410
Median (Full Range)
Unit of Measure: weeks
NA [1] 
(0 to 103)
NA [1] 
(0 to 108)
[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.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments Time to onset CDP at week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0139
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.37 to 0.90
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 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 411 410
Measure Type: Number
Unit of Measure: lesions
337 21
Show Statistical Analysis 1 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
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 0.058
Confidence Interval 95%
0.032 to 0.104
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 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 411 410
Measure Type: Number
Unit of Measure: lesions
1916 430
Show Statistical Analysis 1 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
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 0.229
Confidence Interval 95%
0.174 to 0.300
Estimation Comments Adjusted by baseline T2 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.
5.Secondary Outcome
Title Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
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 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 306 310
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.42
(8.94 to 16.64)
20.00
(15.69 to 24.89)
Show Statistical Analysis 1 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0106
Comments [Not Specified]
Method CMH Chi-Squared test (stratified)
Comments CMH (Cochran-Mantel-Haenszel) Chi-Squared 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 1.61
Confidence Interval (2-Sided) 95%
1.11 to 2.33
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 108
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 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 411 410
Median (Full Range)
Unit of Measure: weeks
NA [1] 
(0 to 103)
NA [1] 
(0 to 108)
[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.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a 44 mcg SC, Ocrelizumab
Comments Time to onset CDP at week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0278
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.34 to 0.95
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 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 411 410
Measure Type: Number
Unit of Measure: lesions
1307 564
Show Statistical Analysis 1 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
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 0.428
Confidence Interval 95%
0.328 to 0.557
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
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 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 411 410
Mean (Standard Error)
Unit of Measure: Z-score
Unadjusted Baseline mean (n= 359, 360) 0.028  (0.034) -0.012  (0.040)
Adjusted Week 96 mean (n= 308, 322) 0.174  (0.031) 0.213  (0.031)
Show Statistical Analysis 1 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.3261
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 0.039
Confidence Interval (2-Sided) 95%
-0.039 to 0.116
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.039
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
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.
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 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 267 281
Mean (Standard Error)
Unit of Measure: percent change
-0.741  (0.046) -0.572  (0.044)
Show Statistical Analysis 1 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0042
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 0.168
Confidence Interval (2-Sided) 95%
0.053 to 0.283
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.058
Estimation Comments Difference in the rate of brain volume loss: 22.8%. 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
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 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 411 410
Mean (Standard Error)
Unit of Measure: t-score
Unadjusted Baseline mean (n= 338, 357) 45.399  (0.529) 45.065  (0.507)
Adjusted mean change at week 96 (n= 276, 315) -0.657  (0.475) 0.036  (0.456)
Show Statistical Analysis 1 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
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.2193
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 0.693
Confidence Interval (2-Sided) 95%
-0.414 to 1.800
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
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 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 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 291 289
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27.1
(22.1 to 32.6)
47.4
(41.5 to 53.3)
Show Statistical Analysis 1 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
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 1.74
Confidence Interval (2-Sided) 95%
1.39 to 2.17
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 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 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 409 408
Measure Type: Number
Unit of Measure: Participants
331 327
13.Secondary Outcome
Title Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC)
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 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 393
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter*day
3513  (955)
14.Secondary Outcome
Title Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
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
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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 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 409 408
Measure Type: Number
Unit of Measure: Participants
Positive sample at baseline (n= 397, 396) 2 1
Positive for ADA post-baseline (n= 401, 402) 2 1
Time Frame Baseline to week 96 (Double Blind Treatment Period)
Adverse Event Reporting Description [Not Specified]
 
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 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.
All-Cause Mortality
Interferon Beta-1a 44 mcg SC Ocrelizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Interferon Beta-1a 44 mcg SC Ocrelizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   32/409 (7.82%)   28/408 (6.86%) 
Blood and lymphatic system disorders     
Leukopenia  1  1/409 (0.24%)  0/408 (0.00%) 
Cardiac disorders     
Atrial flutter  1  0/409 (0.00%)  1/408 (0.25%) 
Cardiac failure congestive  1  0/409 (0.00%)  1/408 (0.25%) 
Eye disorders     
Retinal artery occlusion  1  1/409 (0.24%)  0/408 (0.00%) 
Gastrointestinal disorders     
Gastritis  1  0/409 (0.00%)  1/408 (0.25%) 
Pancreatitis  1  0/409 (0.00%)  1/408 (0.25%) 
Pancreatitis acute  1  0/409 (0.00%)  1/408 (0.25%) 
General disorders     
Chest pain  1  0/409 (0.00%)  2/408 (0.49%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/409 (0.00%)  2/408 (0.49%) 
Cholecystitis  1  0/409 (0.00%)  1/408 (0.25%) 
Cholecystitis chronic  1  0/409 (0.00%)  1/408 (0.25%) 
Immune system disorders     
Drug hypersensitivity  1  1/409 (0.24%)  1/408 (0.25%) 
Infections and infestations     
Cellulitis  1  1/409 (0.24%)  2/408 (0.49%) 
Abscess limb  1  2/409 (0.49%)  0/408 (0.00%) 
Appendicitis  1  2/409 (0.49%)  0/408 (0.00%) 
Acute tonsillitis  1  1/409 (0.24%)  0/408 (0.00%) 
Biliary sepsis  1  0/409 (0.00%)  1/408 (0.25%) 
Device related infection  1  0/409 (0.00%)  1/408 (0.25%) 
Enterocolitis infectious  1  1/409 (0.24%)  0/408 (0.00%) 
Gastroenteritis  1  1/409 (0.24%)  0/408 (0.00%) 
Herpes simplex  1  0/409 (0.00%)  1/408 (0.25%) 
Injection site cellulitis  1  1/409 (0.24%)  0/408 (0.00%) 
Perirectal abscess  1  1/409 (0.24%)  0/408 (0.00%) 
Septic arthritis staphylococcal  1  1/409 (0.24%)  0/408 (0.00%) 
Urinary tract infection  1  1/409 (0.24%)  0/408 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  1/409 (0.24%)  0/408 (0.00%) 
Craniocerebral injury  1  0/409 (0.00%)  1/408 (0.25%) 
Hand fracture  1  1/409 (0.24%)  0/408 (0.00%) 
Humerus fracture  1  0/409 (0.00%)  1/408 (0.25%) 
Infusion related reaction  1  0/409 (0.00%)  1/408 (0.25%) 
Multiple injuries  1  1/409 (0.24%)  0/408 (0.00%) 
Overdose  1  1/409 (0.24%)  0/408 (0.00%) 
Post procedural haematoma  1  1/409 (0.24%)  0/408 (0.00%) 
Procedural pain  1  0/409 (0.00%)  1/408 (0.25%) 
Tibia fracture  1  1/409 (0.24%)  0/408 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  0/409 (0.00%)  1/408 (0.25%) 
Rheumatoid Arthritis  1  1/409 (0.24%)  0/408 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Invasive ductal breast carcinoma  1  0/409 (0.00%)  2/408 (0.49%) 
Uterine leiomyoma  1  2/409 (0.49%)  0/408 (0.00%) 
Mantle cell lymphoma  1  1/409 (0.24%)  0/408 (0.00%) 
Renal cancer  1  0/409 (0.00%)  1/408 (0.25%) 
Salivary gland adenoma  1  1/409 (0.24%)  0/408 (0.00%) 
Nervous system disorders     
Multiple sclerosis relapse  1  3/409 (0.73%)  0/408 (0.00%) 
Epilepsy  1  1/409 (0.24%)  1/408 (0.25%) 
Seizure  1  0/409 (0.00%)  2/408 (0.49%) 
Aphasia  1  1/409 (0.24%)  0/408 (0.00%) 
Dizziness  1  0/409 (0.00%)  1/408 (0.25%) 
Dysarthria  1  1/409 (0.24%)  0/408 (0.00%) 
Ruptured cerebral aneurysm  1  1/409 (0.24%)  0/408 (0.00%) 
Sciatica  1  0/409 (0.00%)  1/408 (0.25%) 
Psychiatric disorders     
Depression  1  0/409 (0.00%)  2/408 (0.49%) 
Anxiety  1  0/409 (0.00%)  1/408 (0.25%) 
Completed suicide  1  1/409 (0.24%)  0/408 (0.00%) 
Suicide attempt  1  0/409 (0.00%)  1/408 (0.25%) 
Reproductive system and breast disorders     
Endometriosis  1  0/409 (0.00%)  1/408 (0.25%) 
Menorrhagia  1  0/409 (0.00%)  1/408 (0.25%) 
Ovarian cyst  1  1/409 (0.24%)  0/408 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Hyperventilation  1  1/409 (0.24%)  0/408 (0.00%) 
Sinus congestion  1  1/409 (0.24%)  0/408 (0.00%) 
Surgical and medical procedures     
Mammoplasty  1  1/409 (0.24%)  0/408 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Interferon Beta-1a 44 mcg SC Ocrelizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   257/409 (62.84%)   241/408 (59.07%) 
General disorders     
Influenza like illness  1  85/409 (20.78%)  15/408 (3.68%) 
Injection site erythema  1  74/409 (18.09%)  0/408 (0.00%) 
Fatigue  1  28/409 (6.85%)  21/408 (5.15%) 
Infections and infestations     
Urinary tract infection  1  56/409 (13.69%)  52/408 (12.75%) 
Upper respiratory tract infection  1  35/409 (8.56%)  59/408 (14.46%) 
Nasopharyngitis  1  43/409 (10.51%)  43/408 (10.54%) 
Sinusitis  1  25/409 (6.11%)  19/408 (4.66%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  30/409 (7.33%)  125/408 (30.64%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  28/409 (6.85%)  25/408 (6.13%) 
Back pain  1  20/409 (4.89%)  25/408 (6.13%) 
Nervous system disorders     
Headache  1  54/409 (13.20%)  33/408 (8.09%) 
Psychiatric disorders     
Depression  1  24/409 (5.87%)  28/408 (6.86%) 
Insomnia  1  15/409 (3.67%)  21/408 (5.15%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
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
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Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
EMail: genentech@druginfo.com
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01247324     History of Changes
Other Study ID Numbers: WA21092
2010-020337-99 ( EudraCT Number )
First Submitted: November 23, 2010
First Posted: November 24, 2010
Results First Submitted: March 30, 2017
Results First Posted: July 18, 2017
Last Update Posted: July 10, 2019