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A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT00676715
Recruitment Status : Active, not recruiting
First Posted : May 13, 2008
Results First Posted : May 11, 2017
Last Update Posted : December 12, 2018
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Multiple Sclerosis, Relapsing-Remitting
Interventions Drug: Placebo
Drug: Ocrelizumab
Drug: Avonex
Enrollment 220
Recruitment Details  
Pre-assignment Details Total 220 participants were randomized, out of which 218 participants received study treatment.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days. Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Period Title: Overall Study
Started 54 55 55 54
Completed 14 8 14 14
Not Completed 40 47 41 40
Reason Not Completed
Withdrawal by Subject             7             9             10             10
Other             2             6             4             3
Lost to Follow-up             1             1             7             3
Death             1             1             1             0
Adverse Event             0             1             2             0
Participants Ongoing             29             29             17             24
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex Total
Hide Arm/Group Description Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days. Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. Total of all reporting groups
Overall Number of Baseline Participants 54 55 55 54 218
Hide Baseline Analysis Population Description
The safety population included all participants who received any study drug and underwent at least one assessment of safety.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants 55 participants 55 participants 54 participants 218 participants
38.0  (8.8) 35.6  (8.5) 38.5  (8.7) 38.1  (9.3) 37.6  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 55 participants 55 participants 54 participants 218 participants
Female
36
  66.7%
35
  63.6%
38
  69.1%
32
  59.3%
141
  64.7%
Male
18
  33.3%
20
  36.4%
17
  30.9%
22
  40.7%
77
  35.3%
1.Primary Outcome
Title Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain
Hide Description Mean of total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 12, 16, 20, 24 was determined using average imputation method.
Time Frame Week 12 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug. Here, number of participants analysed signifies the participants who were evaluable for the outcome.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 51 52 52
Mean (Standard Deviation)
Unit of Measure: Lesion
5.6  (12.53) 0.6  (1.52) 0.2  (0.65) 6.9  (16.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
Comments Van Elteren test is stratified by region and presence of baseline gadolinium-enhancing lesions (absent or present).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
Comments Van Elteren test is stratified by region and presence of baseline gadolinium-enhancing lesions (absent or present).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments Van Elteren test is stratified by region and presence of baseline gadolinium-enhancing lesions (absent or present).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7496
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments [Not Specified]
2.Secondary Outcome
Title Annualized Protocol Defined Relapse Rate at Week 24
Hide Description Adjusted annualized relapse rate for geographical region.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 55 55 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Number of relapses
0.557
(0.370 to 0.839)
0.127
(0.054 to 0.299)
0.213
(0.110 to 0.414)
0.364
(0.220 to 0.602)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
Comments Poisson model was fitted for adjusting for geographic region only.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Poisson model
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
Comments Poisson model was fitted for adjusting for geographic region only.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0136
Comments [Not Specified]
Method Poisson model
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments Poisson model was fitted for adjusting for geographic region only.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1814
Comments [Not Specified]
Method Poisson model
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Remained Relapse Free at Week 24
Hide Description Percentage of participants who remained relapse free at week 24 were reported.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 55 55 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.9
(64.5 to 87.3)
85.5
(76.1 to 94.8)
87.3
(78.5 to 96.1)
77.8
(66.7 to 88.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1978
Comments [Not Specified]
Method Cochran-Mantel-Haenszel chi-square test
Comments Cochran-Mantel-Haenszel (CMH) chi-square test stratified by geographical region only.
Method of Estimation Estimation Parameter Relative risk (RR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.27 to 1.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1310
Comments [Not Specified]
Method CMH chi-square test
Comments CMH chi-square test stratified by geographical region only.
Method of Estimation Estimation Parameter Relative risk (RR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.23 to 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8206
Comments [Not Specified]
Method CMH chi-square tes
Comments CMH chi-square test stratified by geographical region only.
Method of Estimation Estimation Parameter Relative risk (RR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.46 to 1.84
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24
Hide Description Change from baseline in total volume of T2 lesions on MRI scans of the Brain at week 24 was reported.
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug. Here, n signifies the number of participants evaluated at specified time points.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 55 55 54
Mean (Standard Deviation)
Unit of Measure: Cubic Millimeter (mm^3)
Baseline (n= 47, 51, 53, 49) 8950.84  (9776.261) 13972.61  (19930.158) 13178.30  (14271.383) 13209.11  (17206.511)
Change at Week 24 (n= 43, 45, 46, 46) -112.31  (1464.206) -878.84  (2756.839) -600.89  (2105.964) 1040.06  (4510.140)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1391
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1596
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4740
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
5.Secondary Outcome
Title Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain
Hide Description Total number of new gadolinium-enhancing T1 lesions observed by MRI scans of the brain were reported.
Time Frame Weeks 4 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug. Here, number of participants analysed signifies the participants who were evaluable for the outcome.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 51 52 52
Mean (Standard Deviation)
Unit of Measure: Lesions
5.1  (11.99) 0.8  (1.95) 0.8  (2.16) 6.2  (13.79)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
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 Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
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 Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4985
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
6.Secondary Outcome
Title Total Number of Gadolinium-Enhancing T1 Lesions at Weeks
Hide Description Total number of gadolinium-enhancing T1 lesions at weeks were reported.
Time Frame Weeks 4 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat population includes all randomized participants who had received any study drug. Here, number of participants analysed signifies the participants who were evaluable for the outcome.
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description:
Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.
Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
Overall Number of Participants Analyzed 54 51 52 52
Mean (Standard Deviation)
Unit of Measure: Lesions
8.7  (17.54) 2.5  (5.10) 1.8  (5.26) 10.3  (22.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 600 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ocrelizumab 1000 mg
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 Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Avonex
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2725
Comments [Not Specified]
Method Van Elteren Test (stratified)
Comments Van Elteren test is stratified by region only.
Time Frame Up to clinical cutoff date 22 January 2015 (approximately 7 years)
Adverse Event Reporting Description The safety population included all participants who received any study drug and underwent at least one assessment of safety.
 
Arm/Group Title Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Hide Arm/Group Description Participants received two IV infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days. Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
All-Cause Mortality
Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/54 (11.11%)   8/55 (14.55%)   11/55 (20.00%)   13/54 (24.07%) 
Blood and lymphatic system disorders         
Immune thrombocytopenic purpura † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Ear and labyrinth disorders         
Vertigo † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Eye disorders         
Retinal artery occlusion † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Gastrointestinal disorders         
Abdominal pain upper † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Colitis † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Inguinal hernia strangulated † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Large intestine polyp † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Salivary duct inflammation † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Subileus † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
General disorders         
Death † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Drug withdrawal syndrome † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Systemic inflammatory response syndrome † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Immune system disorders         
Hypersensitivity † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Infections and infestations         
Anal abscess † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Bronchitis † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Bronchopneumonia † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Diverticulitis † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Cystitis † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Encephalitis † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Gastroenteritis † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Gingivitis † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Hepatitis A † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Influenza † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Oral herpes † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Pyelonephritis acute † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Injury † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Muscular weakness † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Squamous cell carcinoma † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Nervous system disorders         
Multiple sclerosis relapse † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  2/54 (3.70%) 
Epilepsy † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Muscle spasticity † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Seizure † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Pregnancy, puerperium and perinatal conditions         
Pregnancy † 1  0/54 (0.00%)  1/55 (1.82%)  0/55 (0.00%)  0/54 (0.00%) 
Psychiatric disorders         
Acute psychosis † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Anxiety † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Depression † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Suicidal ideation † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Suicide attempt † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Renal and urinary disorders         
Calculus ureteric † 1  0/54 (0.00%)  0/55 (0.00%)  1/55 (1.82%)  0/54 (0.00%) 
Reproductive system and breast disorders         
Ovarian mass † 1  0/54 (0.00%)  0/55 (0.00%)  0/55 (0.00%)  1/54 (1.85%) 
Uterine prolapse † 1  1/54 (1.85%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (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%
Placebo Ocrelizumab 600 mg Ocrelizumab 1000 mg Avonex
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/54 (90.74%)   45/55 (81.82%)   44/55 (80.00%)   45/54 (83.33%) 
Cardiac disorders         
Palpitations † 1  0/54 (0.00%)  1/55 (1.82%)  3/55 (5.45%)  1/54 (1.85%) 
Gastrointestinal disorders         
Nausea † 1  1/54 (1.85%)  2/55 (3.64%)  6/55 (10.91%)  4/54 (7.41%) 
Diarrhoea † 1  3/54 (5.56%)  3/55 (5.45%)  4/55 (7.27%)  1/54 (1.85%) 
Constipation † 1  2/54 (3.70%)  3/55 (5.45%)  3/55 (5.45%)  1/54 (1.85%) 
General disorders         
Fatigue † 1  4/54 (7.41%)  6/55 (10.91%)  10/55 (18.18%)  4/54 (7.41%) 
Influenza like illness † 1  0/54 (0.00%)  1/55 (1.82%)  1/55 (1.82%)  11/54 (20.37%) 
Asthenia † 1  3/54 (5.56%)  1/55 (1.82%)  2/55 (3.64%)  1/54 (1.85%) 
Pyrexia † 1  0/54 (0.00%)  3/55 (5.45%)  2/55 (3.64%)  1/54 (1.85%) 
Chills † 1  0/54 (0.00%)  1/55 (1.82%)  1/55 (1.82%)  3/54 (5.56%) 
Infections and infestations         
Nasopharyngitis † 1  9/54 (16.67%)  11/55 (20.00%)  11/55 (20.00%)  8/54 (14.81%) 
Urinary tract infection † 1  11/54 (20.37%)  6/55 (10.91%)  10/55 (18.18%)  9/54 (16.67%) 
Upper respiratory tract infection † 1  8/54 (14.81%)  13/55 (23.64%)  10/55 (18.18%)  6/54 (11.11%) 
Influenza † 1  3/54 (5.56%)  3/55 (5.45%)  7/55 (12.73%)  3/54 (5.56%) 
Respiratory tract infection † 1  6/54 (11.11%)  4/55 (7.27%)  2/55 (3.64%)  3/54 (5.56%) 
Gastroenteritis † 1  1/54 (1.85%)  3/55 (5.45%)  1/55 (1.82%)  1/54 (1.85%) 
Bronchitis † 1  5/54 (9.26%)  3/55 (5.45%)  2/55 (3.64%)  1/54 (1.85%) 
Oral herpes † 1  4/54 (7.41%)  3/55 (5.45%)  1/55 (1.82%)  3/54 (5.56%) 
Pharyngitis † 1  5/54 (9.26%)  3/55 (5.45%)  1/55 (1.82%)  3/54 (5.56%) 
Sinusitis † 1  4/54 (7.41%)  3/55 (5.45%)  2/55 (3.64%)  2/54 (3.70%) 
Cystitis † 1  2/54 (3.70%)  2/55 (3.64%)  4/55 (7.27%)  0/54 (0.00%) 
Gastroenteritis viral † 1  0/54 (0.00%)  5/55 (9.09%)  1/55 (1.82%)  0/54 (0.00%) 
Respiratory tract infection viral † 1  2/54 (3.70%)  3/55 (5.45%)  0/55 (0.00%)  1/54 (1.85%) 
Injury, poisoning and procedural complications         
Infusion related reaction † 1  28/54 (51.85%)  25/55 (45.45%)  29/55 (52.73%)  20/54 (37.04%) 
Ligament sprain † 1  1/54 (1.85%)  1/55 (1.82%)  5/55 (9.09%)  1/54 (1.85%) 
Thermal burn † 1  3/54 (5.56%)  1/55 (1.82%)  3/55 (5.45%)  0/54 (0.00%) 
Fall † 1  0/54 (0.00%)  1/55 (1.82%)  3/55 (5.45%)  0/54 (0.00%) 
Laceration † 1  0/54 (0.00%)  1/55 (1.82%)  3/55 (5.45%)  0/54 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain † 1  8/54 (14.81%)  5/55 (9.09%)  4/55 (7.27%)  7/54 (12.96%) 
Arthralgia † 1  6/54 (11.11%)  5/55 (9.09%)  2/55 (3.64%)  4/54 (7.41%) 
Pain in extremity † 1  5/54 (9.26%)  2/55 (3.64%)  5/55 (9.09%)  1/54 (1.85%) 
Muscular weakness † 1  0/54 (0.00%)  4/55 (7.27%)  2/55 (3.64%)  1/54 (1.85%) 
Myalgia † 1  0/54 (0.00%)  3/55 (5.45%)  2/55 (3.64%)  3/54 (5.56%) 
Musculoskeletal pain † 1  0/54 (0.00%)  3/55 (5.45%)  3/55 (5.45%)  1/54 (1.85%) 
Nervous system disorders         
Multiple sclerosis relapse † 1  23/54 (42.59%)  19/55 (34.55%)  19/55 (34.55%)  27/54 (50.00%) 
Headache † 1  13/54 (24.07%)  9/55 (16.36%)  10/55 (18.18%)  11/54 (20.37%) 
Dizziness † 1  4/54 (7.41%)  4/55 (7.27%)  3/55 (5.45%)  1/54 (1.85%) 
Paraesthesia † 1  1/54 (1.85%)  4/55 (7.27%)  6/55 (10.91%)  1/54 (1.85%) 
Hypoaesthesia † 1  1/54 (1.85%)  2/55 (3.64%)  4/55 (7.27%)  3/54 (5.56%) 
Migraine † 1  2/54 (3.70%)  4/55 (7.27%)  2/55 (3.64%)  1/54 (1.85%) 
Syncope † 1  3/54 (5.56%)  0/55 (0.00%)  0/55 (0.00%)  0/54 (0.00%) 
Psychiatric disorders         
Depression † 1  3/54 (5.56%)  6/55 (10.91%)  5/55 (9.09%)  4/54 (7.41%) 
Anxiety † 1  3/54 (5.56%)  5/55 (9.09%)  3/55 (5.45%)  6/54 (11.11%) 
Insomnia † 1  2/54 (3.70%)  3/55 (5.45%)  9/55 (16.36%)  1/54 (1.85%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  1/54 (1.85%)  2/55 (3.64%)  1/55 (1.82%)  3/54 (5.56%) 
Asthma † 1  0/54 (0.00%)  0/55 (0.00%)  3/55 (5.45%)  1/54 (1.85%) 
Skin and subcutaneous tissue disorders         
Rash † 1  3/54 (5.56%)  2/55 (3.64%)  4/55 (7.27%)  2/54 (3.70%) 
Vascular disorders         
Hypertension † 1  2/54 (3.70%)  5/55 (9.09%)  0/55 (0.00%)  1/54 (1.85%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
[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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00676715     History of Changes
Other Study ID Numbers: ACT4422g
2007-006338-32 ( EudraCT Number )
WA21493 ( Other Identifier: Hoffmann-La Roche )
First Submitted: May 9, 2008
First Posted: May 13, 2008
Results First Submitted: March 31, 2017
Results First Posted: May 11, 2017
Last Update Posted: December 12, 2018