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Trial record 2 of 2 for:    camms223

A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting 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: NCT00050778
Recruitment Status : Completed
First Posted : December 23, 2002
Results First Posted : August 25, 2009
Last Update Posted : January 8, 2015
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Sclerosis, Relapsing-Remitting
Interventions Biological: Interferon beta-1a
Biological: Alemtuzumab 12 mg
Biological: Alemtuzumab 24 mg
Enrollment 334
Recruitment Details The study was conducted at 49 investigational sites in the United States, United Kingdom, and Eastern Europe between December 04, 2002 and January 12, 2010.
Pre-assignment Details  
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg
Hide Arm/Group Description Interferon beta-1a (Rebif®) 44 micrograms (mcg) subcutaneously 3-times weekly for 36 months. Alemtuzumab (Lemtrada™) 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the cluster of differentiation 4+ [CD4+] T-cell count was >=100*10^6 cells per liter). Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Period Title: Overall Study
Started 111 [1] 113 110
Treated 107 108 108
Completed 66 92 92
Not Completed 45 21 18
Reason Not Completed
Adverse Event             13             3             2
Death             0             1             1
Lack of Efficacy             16             2             2
Lost to Follow-up             0             2             4
Physician Decision             3             0             2
Protocol Violation             2             0             1
Withdrawal by Subject             6             8             4
Randomized but not treated             4             5             2
Familial and personal reasons             1             0             0
[1]
Randomized.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Total
Hide Arm/Group Description Interferon beta-1a 44 mcg subcutaneously 3-times weekly for 36 months. Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter). Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter). Total of all reporting groups
Overall Number of Baseline Participants 111 112 110 333
Hide Baseline Analysis Population Description
FAS population included all randomized participants who had correct diagnosis of MS at entry. One participant was included in safety but excluded from efficacy analysis as initial multiple sclerosis diagnosis was incorrect.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 112 participants 110 participants 333 participants
32.8  (8.82) 31.9  (8.01) 32.2  (8.76) 32.3  (8.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 110 participants 333 participants
Female
71
  64.0%
72
  64.3%
71
  64.5%
214
  64.3%
Male
40
  36.0%
40
  35.7%
39
  35.5%
119
  35.7%
Time Since First Relapse  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 111 participants 112 participants 110 participants 333 participants
1.4
(0.2 to 6.3)
1.3
(0.1 to 3.5)
1.2
(0.3 to 3.2)
1.3
(0.1 to 6.3)
Number of Relapse Episodes in the Preceding 2 Years   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 110 participants 333 participants
0 Relapse 0 2 1 3
1 Relapse 8 5 13 26
2 Relapses 73 58 56 187
Greater than or equal to 3 Relapses 30 47 40 117
[1]
Measure Description: Number of participants with 0, 1, 2 or greater than or equal to 3 relapses are reported.
Total Number of Relapses  
Measure Type: Number
Unit of measure:  Relapses
Number Analyzed 111 participants 112 participants 110 participants 333 participants
293 301 290 884
Expanded Disability Status Scale (EDSS) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 111 participants 112 participants 110 participants 333 participants
1.9  (0.81) 2.0  (0.73) 2.0  (0.73) 1.9  (0.76)
[1]
Measure Description: EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS). Number of participants evaluable for this Baseline characteristic were 110, 112 and 110 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively.
Time Constant 1 (T1) Cerebral Volume   [1] 
Mean (Standard Deviation)
Unit of measure:  Cubic centimeter
Number Analyzed 111 participants 112 participants 110 participants 333 participants
317.5  (24.70) 320.8  (27.15) 320.5  (24.99) 319.6  (25.61)
[1]
Measure Description: Number of participants evaluable for this Baseline characteristic were 103, 107 and 107 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively. Partial brain volumes were measured using the technique of Losseff et al. (1996).
Time Constant 2 (T2) Lesion Volume   [1] 
Mean (Standard Deviation)
Unit of measure:  Cubic centimeter
Number Analyzed 111 participants 112 participants 110 participants 333 participants
15.8  (15.23) 17.2  (23.84) 17.8  (17.45) 17.0  (19.19)
[1]
Measure Description: Number of participants evaluable for this Baseline characteristic were 102, 106 and 107 in Interferon Beta-1a, Alemtuzumab 12 mg and Alemtuzumab 24 mg arm, respectively.
1.Primary Outcome
Title Probability of Participants With Sustained Accumulation of Disability (SAD)
Hide Description EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population included all randomized participants who had correct diagnosis of MS at entry.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description:
Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Overall Number of Participants Analyzed 111 112 110 222
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of participants with SAD
0.27
(0.193 to 0.380)
0.08
(0.043 to 0.165)
0.09
(0.052 to 0.169)
0.09
(0.057 to 0.139)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 12 mg
Comments Cox proportional hazards (PH) regression model using treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country) as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments An alpha-sharing approach was used to adjust for multiple treatment group comparisons, endpoints, and two pre-planned interim analyses, including a Lan-Demets error-spending function. Pre-specified threshold for statistical significance was 0.0165.
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.110 to 0.545
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 24 mg
Comments Cox PH regression model using treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country) as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments An alpha-sharing approach was used to adjust for multiple treatment group comparisons, endpoints, and two pre-planned interim analyses, including a Lan-Demets error-spending function. Pre-specified threshold for statistical significance was 0.0165.
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.151 to 0.658
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab (Pooled)
Comments Cox PH regression model using treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country) as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.152 to 0.515
Estimation Comments [Not Specified]
2.Primary Outcome
Title Annualized Relapse Rate
Hide Description Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had correct diagnosis of MS at entry.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description:
Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Overall Number of Participants Analyzed 111 112 110 222
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per participant per year
0.37
(0.297 to 0.449)
0.12
(0.091 to 0.171)
0.09
(0.064 to 0.133)
0.11
(0.085 to 0.137)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 12 mg
Comments Treatment effects were estimated using an Anderson-Gill multiplicative intensity model with robust variance estimation. Covariates included treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments An alpha-sharing approach was used to adjust for multiple treatment group comparisons, endpoints, and two pre-planned interim analyses, including a Lan-Demets error-spending function. Pre-specified threshold for statistical significance was 0.0040.
Method Andersen-Gill Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.196 to 0.552
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 24 mg
Comments Treatment effects were estimated using an Anderson-Gill multiplicative intensity model with robust variance estimation. Covariates included treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments An alpha-sharing approach was used to adjust for multiple treatment group comparisons, endpoints, and two pre-planned interim analyses, including a Lan-Demets error-spending function. Pre-specified threshold for statistical significance was 0.0040.
Method Andersen-Gill Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.126 to 0.431
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab (Pooled)
Comments Treatment effects were estimated using an Anderson-Gill multiplicative intensity model with robust variance estimation. Covariates included treatment group, Baseline EDSS group (grouped by less than or equal to 1.5 and greater than 1.5), and country (investigative center grouped by country).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Andersen-Gill Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.176 to 0.441
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment
Hide Description Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.
Time Frame Year 3
Hide Outcome Measure Data
Hide Analysis Population Description
FAS population included all randomized participants who had correct diagnosis of MS at entry.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description:
Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Overall Number of Participants Analyzed 111 112 110 222
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of participants
0.50
(0.395 to 0.602)
0.76
(0.667 to 0.832)
0.84
(0.748 to 0.894)
0.80
(0.737 to 0.847)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 12 mg
Comments Cox PH regression model with treatment group indicator, Baseline EDSS and country as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment effect
Estimated Value 62.64
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 24 mg
Comments Cox PH regression model with treatment group indicator, Baseline EDSS and country as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment effect
Estimated Value 76.71
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab (Pooled)
Comments Cox PH regression model with treatment group indicator, Baseline EDSS and country as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cox Proportional Hazards Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment effect
Estimated Value 70.13
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in T1 Cerebral Volume at Year 3
Hide Description Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100*([brain volume at Year 3] minus [brain volume at Baseline]) divided by [brain volume at Baseline]).
Time Frame Baseline, Year 3
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T1 brain volume at Baseline and Year 3.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description:
Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Overall Number of Participants Analyzed 67 83 90 173
Mean (Standard Deviation)
Unit of Measure: percent change
-1.9  (4.48) -0.8  (3.66) -0.4  (4.27) -0.6  (3.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 12 mg
Comments Ranked analysis of covariance (ANCOVA) model using Baseline MRI-T1 brain volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0885
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 24 mg
Comments Ranked ANCOVA model using Baseline MRI-T1 brain volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0195
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab (Pooled)
Comments Ranked ANCOVA model using Baseline MRI-T1 brain volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0215
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in MRI T2 Lesion Volume at Year 3
Hide Description Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100*([lesion volume at Year 3] minus [lesion volume at Baseline]) divided by [lesion volume at Baseline]).
Time Frame Baseline, Year 3
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T2 lesion volume at Baseline and Year 3.
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description:
Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.
Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians’ discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Overall Number of Participants Analyzed 66 81 88 169
Mean (Standard Deviation)
Unit of Measure: percent change
23.4  (134.3) -11.4  (38.8) -8.9  (41.1) -10.1  (39.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 12 mg
Comments Ranked ANCOVA model using Baseline MRI-T2 lesion volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3077
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab 24 mg
Comments Ranked ANCOVA model using Baseline MRI-T2 lesion volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3632
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Interferon Beta-1a, Alemtuzumab (Pooled)
Comments Ranked ANCOVA model using Baseline MRI-T2 lesion volume, EDSS group, country, and treatment as covariates was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2758
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame First dose of study drug up to last follow-up (80.6 months)
Adverse Event Reporting Description If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
 
Arm/Group Title Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Hide Arm/Group Description Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months. Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter). Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter). Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
All-Cause Mortality
Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Interferon Beta-1a Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   29/107 (27.10%)   30/108 (27.78%)   33/108 (30.56%)   63/216 (29.17%) 
Blood and lymphatic system disorders         
Autoimmune thrombocytopenia * 1  0/107 (0.00%)  1/108 (0.93%)  1/108 (0.93%)  2/216 (0.93%) 
Idiopathic thrombocytopenic purpura * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Neutropenia * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Thrombocytopenia * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Cardiac disorders         
Acute myocardial infarction * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Angina pectoris * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Arrhythmia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Atrial fibrillation * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Bradycardia * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Cardiovascular disorder * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Myocardial infarction * 1  3/107 (2.80%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Pericarditis * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Endocrine disorders         
Autoimmune thyroiditis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Basedow's disease * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Thyroiditis subacute * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Eye disorders         
Cataract * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Diplopia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Exophthalmos * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Vision blurred * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Visual acuity reduced * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Gastrointestinal disorders         
Abdominal hernia * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Dyspepsia * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Enterocutaneous fistula * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Erosive oesophagitis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Gastric ulcer * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Gastritis * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Gastroduodenitis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Hypoaesthesia oral * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Ileus * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Ileus paralytic * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Nausea * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Paraesthesia oral * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Peritonitis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Salivary gland calculus * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Vomiting * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
General disorders         
Adverse drug reaction * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Asthenia * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Chest discomfort * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Death * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Fatigue * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Gait disturbance * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Infusion related reaction * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Pyrexia * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Hepatobiliary disorders         
Hepatic failure * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Infections and infestations         
Appendicitis * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Bronchitis * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Catheter bacteraemia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Cellulitis of male external genital organ * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Cervicitis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Gastroenteritis * 1  0/107 (0.00%)  1/108 (0.93%)  1/108 (0.93%)  2/216 (0.93%) 
Herpes ophthalmic * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Herpes zoster * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Meningitis listeria * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Meningitis viral * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Sepsis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Sinusitis * 1  1/107 (0.93%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Subcutaneous abscess * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Urinary tract infection * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Varicella * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Viral infection * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Injury, poisoning and procedural complications         
Alcohol poisoning * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Fibula fracture * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Joint injury * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Limb traumatic amputation * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Procedural pain * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Rib fracture * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Tibia fracture * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Traumatic brain injury * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Traumatic lung injury * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Aspartate aminotransferase increased * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Hepatic enzyme increased * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Transaminases increased * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Metabolism and nutrition disorders         
Dehydration * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Intervertebral disc protrusion * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Muscular weakness * 1  2/107 (1.87%)  2/108 (1.85%)  1/108 (0.93%)  3/216 (1.39%) 
Osteoarthritis * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Pain in extremity * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Polyarthritis * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acoustic neuroma * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Angiomyolipoma * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Basal cell carcinoma * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Breast cancer * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Cervix carcinoma * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Colon cancer * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Glomus tumour * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Thyroid cancer * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Uterine leiomyoma * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Nervous system disorders         
Ataxia * 1  2/107 (1.87%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Balance disorder * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Carpal tunnel syndrome * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Cerebellar ataxia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Cerebral haemorrhage * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Cerebrovascular accident * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Dizziness * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Headache * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Hemiparesis * 1  0/107 (0.00%)  1/108 (0.93%)  1/108 (0.93%)  2/216 (0.93%) 
Hypoaesthesia * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Multiple sclerosis relapse * 1  14/107 (13.08%)  5/108 (4.63%)  9/108 (8.33%)  14/216 (6.48%) 
Myelitis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Paraesthesia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Paraparesis * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Paresis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Sensory disturbance * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Sensory loss * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Syncope * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Pregnancy, puerperium and perinatal conditions         
Abortion * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Abortion missed * 1  0/107 (0.00%)  1/108 (0.93%)  1/108 (0.93%)  2/216 (0.93%) 
Abortion spontaneous * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Abortion threatened * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Psychiatric disorders         
Anxiety * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Bipolar disorder * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Suicide attempt * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Renal and urinary disorders         
Goodpasture's syndrome * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Micturition urgency * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Nephrolithiasis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Urinary incontinence * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Urinary retention * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Reproductive system and breast disorders         
Dysmenorrhoea * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Ectropion of cervix * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Endometriosis * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Menometrorrhagia * 1  0/107 (0.00%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Menorrhagia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Metrorrhagia * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Ovarian cyst * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Ovarian cyst ruptured * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Ovarian disorder * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Pelvic pain * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Uterine polyp * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma * 1  0/107 (0.00%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Dyspnoea * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Epistaxis * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Haemothorax * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Pleural effusion * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Pulmonary embolism * 1  1/107 (0.93%)  0/108 (0.00%)  1/108 (0.93%)  1/216 (0.46%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis * 1  1/107 (0.93%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Vascular disorders         
Hypertension * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Hypotension * 1  0/107 (0.00%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.1
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 Alemtuzumab 12 mg Alemtuzumab 24 mg Alemtuzumab (Pooled)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   106/107 (99.07%)   108/108 (100.00%)   108/108 (100.00%)   216/216 (100.00%) 
Blood and lymphatic system disorders         
Neutropenia * 1  1/107 (0.93%)  6/108 (5.56%)  4/108 (3.70%)  10/216 (4.63%) 
Cardiac disorders         
Palpitations * 1  3/107 (2.80%)  6/108 (5.56%)  8/108 (7.41%)  14/216 (6.48%) 
Tachycardia * 1  6/107 (5.61%)  13/108 (12.04%)  13/108 (12.04%)  26/216 (12.04%) 
Ear and labyrinth disorders         
Vertigo * 1  10/107 (9.35%)  12/108 (11.11%)  11/108 (10.19%)  23/216 (10.65%) 
Endocrine disorders         
Basedow's disease * 1  1/107 (0.93%)  12/108 (11.11%)  6/108 (5.56%)  18/216 (8.33%) 
Hyperthyroidism * 1  1/107 (0.93%)  11/108 (10.19%)  13/108 (12.04%)  24/216 (11.11%) 
Hypothyroidism * 1  1/107 (0.93%)  11/108 (10.19%)  11/108 (10.19%)  22/216 (10.19%) 
Eye disorders         
Diplopia * 1  7/107 (6.54%)  3/108 (2.78%)  6/108 (5.56%)  9/216 (4.17%) 
Vision blurred * 1  4/107 (3.74%)  9/108 (8.33%)  16/108 (14.81%)  25/216 (11.57%) 
Visual acuity reduced * 1  6/107 (5.61%)  4/108 (3.70%)  2/108 (1.85%)  6/216 (2.78%) 
Gastrointestinal disorders         
Abdominal pain * 1  7/107 (6.54%)  6/108 (5.56%)  5/108 (4.63%)  11/216 (5.09%) 
Abdominal pain upper * 1  6/107 (5.61%)  2/108 (1.85%)  4/108 (3.70%)  6/216 (2.78%) 
Constipation * 1  9/107 (8.41%)  9/108 (8.33%)  6/108 (5.56%)  15/216 (6.94%) 
Diarrhoea * 1  7/107 (6.54%)  17/108 (15.74%)  17/108 (15.74%)  34/216 (15.74%) 
Dyspepsia * 1  9/107 (8.41%)  16/108 (14.81%)  13/108 (12.04%)  29/216 (13.43%) 
Gastrooesophageal reflux disease * 1  0/107 (0.00%)  6/108 (5.56%)  7/108 (6.48%)  13/216 (6.02%) 
Nausea * 1  17/107 (15.89%)  32/108 (29.63%)  45/108 (41.67%)  77/216 (35.65%) 
Stomatitis * 1  1/107 (0.93%)  2/108 (1.85%)  9/108 (8.33%)  11/216 (5.09%) 
Toothache * 1  1/107 (0.93%)  1/108 (0.93%)  6/108 (5.56%)  7/216 (3.24%) 
Vomiting * 1  9/107 (8.41%)  18/108 (16.67%)  19/108 (17.59%)  37/216 (17.13%) 
General disorders         
Asthenia * 1  5/107 (4.67%)  18/108 (16.67%)  12/108 (11.11%)  30/216 (13.89%) 
Chest discomfort * 1  3/107 (2.80%)  12/108 (11.11%)  18/108 (16.67%)  30/216 (13.89%) 
Chills * 1  8/107 (7.48%)  19/108 (17.59%)  21/108 (19.44%)  40/216 (18.52%) 
Fatigue * 1  31/107 (28.97%)  47/108 (43.52%)  44/108 (40.74%)  91/216 (42.13%) 
Gait disturbance * 1  13/107 (12.15%)  6/108 (5.56%)  5/108 (4.63%)  11/216 (5.09%) 
Hyperthermia * 1  1/107 (0.93%)  7/108 (6.48%)  5/108 (4.63%)  12/216 (5.56%) 
Influenza like illness * 1  32/107 (29.91%)  21/108 (19.44%)  15/108 (13.89%)  36/216 (16.67%) 
Injection site erythema * 1  35/107 (32.71%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Injection site pain * 1  18/107 (16.82%)  3/108 (2.78%)  0/108 (0.00%)  3/216 (1.39%) 
Injection site reaction * 1  12/107 (11.21%)  1/108 (0.93%)  0/108 (0.00%)  1/216 (0.46%) 
Oedema peripheral * 1  4/107 (3.74%)  6/108 (5.56%)  3/108 (2.78%)  9/216 (4.17%) 
Pain * 1  6/107 (5.61%)  13/108 (12.04%)  14/108 (12.96%)  27/216 (12.50%) 
Pyrexia * 1  11/107 (10.28%)  47/108 (43.52%)  47/108 (43.52%)  94/216 (43.52%) 
Infections and infestations         
Bronchitis * 1  3/107 (2.80%)  11/108 (10.19%)  14/108 (12.96%)  25/216 (11.57%) 
Herpes zoster * 1  1/107 (0.93%)  4/108 (3.70%)  8/108 (7.41%)  12/216 (5.56%) 
Influenza * 1  4/107 (3.74%)  10/108 (9.26%)  3/108 (2.78%)  13/216 (6.02%) 
Nasopharyngitis * 1  14/107 (13.08%)  17/108 (15.74%)  26/108 (24.07%)  43/216 (19.91%) 
Oral herpes * 1  1/107 (0.93%)  7/108 (6.48%)  8/108 (7.41%)  15/216 (6.94%) 
Pharyngitis * 1  4/107 (3.74%)  3/108 (2.78%)  9/108 (8.33%)  12/216 (5.56%) 
Rhinitis * 1  3/107 (2.80%)  9/108 (8.33%)  9/108 (8.33%)  18/216 (8.33%) 
Sinusitis * 1  9/107 (8.41%)  13/108 (12.04%)  18/108 (16.67%)  31/216 (14.35%) 
Upper respiratory tract infection * 1  10/107 (9.35%)  21/108 (19.44%)  28/108 (25.93%)  49/216 (22.69%) 
Urinary tract infection * 1  11/107 (10.28%)  11/108 (10.19%)  17/108 (15.74%)  28/216 (12.96%) 
Viral infection * 1  6/107 (5.61%)  4/108 (3.70%)  2/108 (1.85%)  6/216 (2.78%) 
Injury, poisoning and procedural complications         
Contusion * 1  3/107 (2.80%)  6/108 (5.56%)  15/108 (13.89%)  21/216 (9.72%) 
Investigations         
Alanine aminotransferase increased * 1  9/107 (8.41%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Aspartate aminotransferase increased * 1  6/107 (5.61%)  0/108 (0.00%)  0/108 (0.00%)  0/216 (0.00%) 
Body temperature increased * 1  0/107 (0.00%)  1/108 (0.93%)  6/108 (5.56%)  7/216 (3.24%) 
Weight decreased * 1  2/107 (1.87%)  7/108 (6.48%)  9/108 (8.33%)  16/216 (7.41%) 
Weight increased * 1  7/107 (6.54%)  9/108 (8.33%)  11/108 (10.19%)  20/216 (9.26%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  10/107 (9.35%)  21/108 (19.44%)  11/108 (10.19%)  32/216 (14.81%) 
Back pain * 1  11/107 (10.28%)  17/108 (15.74%)  27/108 (25.00%)  44/216 (20.37%) 
Muscle spasms * 1  11/107 (10.28%)  19/108 (17.59%)  20/108 (18.52%)  39/216 (18.06%) 
Muscle tightness * 1  0/107 (0.00%)  7/108 (6.48%)  2/108 (1.85%)  9/216 (4.17%) 
Muscular weakness * 1  30/107 (28.04%)  17/108 (15.74%)  20/108 (18.52%)  37/216 (17.13%) 
Musculoskeletal pain * 1  9/107 (8.41%)  10/108 (9.26%)  5/108 (4.63%)  15/216 (6.94%) 
Myalgia * 1  9/107 (8.41%)  11/108 (10.19%)  12/108 (11.11%)  23/216 (10.65%) 
Neck pain * 1  5/107 (4.67%)  8/108 (7.41%)  7/108 (6.48%)  15/216 (6.94%) 
Pain in extremity * 1  16/107 (14.95%)  25/108 (23.15%)  32/108 (29.63%)  57/216 (26.39%) 
Nervous system disorders         
Ataxia * 1  13/107 (12.15%)  5/108 (4.63%)  3/108 (2.78%)  8/216 (3.70%) 
Balance disorder * 1  5/107 (4.67%)  7/108 (6.48%)  5/108 (4.63%)  12/216 (5.56%) 
Burning sensation * 1  5/107 (4.67%)  2/108 (1.85%)  8/108 (7.41%)  10/216 (4.63%) 
Coordination abnormal * 1  6/107 (5.61%)  6/108 (5.56%)  4/108 (3.70%)  10/216 (4.63%) 
Dizziness * 1  11/107 (10.28%)  13/108 (12.04%)  29/108 (26.85%)  42/216 (19.44%) 
Dysgeusia * 1  22/107 (20.56%)  18/108 (16.67%)  19/108 (17.59%)  37/216 (17.13%) 
Headache * 1  26/107 (24.30%)  72/108 (66.67%)  85/108 (78.70%)  157/216 (72.69%) 
Hypoaesthesia * 1  24/107 (22.43%)  29/108 (26.85%)  26/108 (24.07%)  55/216 (25.46%) 
Migraine * 1  4/107 (3.74%)  9/108 (8.33%)  6/108 (5.56%)  15/216 (6.94%) 
Multiple sclerosis * 1  5/107 (4.67%)  8/108 (7.41%)  6/108 (5.56%)  14/216 (6.48%) 
Multiple sclerosis relapse * 1  40/107 (37.38%)  27/108 (25.00%)  21/108 (19.44%)  48/216 (22.22%) 
Muscle spasticity * 1  8/107 (7.48%)  4/108 (3.70%)  0/108 (0.00%)  4/216 (1.85%) 
Paraesthesia * 1  18/107 (16.82%)  36/108 (33.33%)  22/108 (20.37%)  58/216 (26.85%) 
Sensory disturbance * 1  8/107 (7.48%)  7/108 (6.48%)  7/108 (6.48%)  14/216 (6.48%) 
Tremor * 1  5/107 (4.67%)  7/108 (6.48%)  6/108 (5.56%)  13/216 (6.02%) 
Pregnancy, puerperium and perinatal conditions         
Pregnancy * 1  9/107 (8.41%)  11/108 (10.19%)  6/108 (5.56%)  17/216 (7.87%) 
Psychiatric disorders         
Anxiety * 1  10/107 (9.35%)  12/108 (11.11%)  20/108 (18.52%)  32/216 (14.81%) 
Depression * 1  20/107 (18.69%)  19/108 (17.59%)  18/108 (16.67%)  37/216 (17.13%) 
Insomnia * 1  17/107 (15.89%)  36/108 (33.33%)  29/108 (26.85%)  65/216 (30.09%) 
Renal and urinary disorders         
Micturition urgency * 1  6/107 (5.61%)  1/108 (0.93%)  6/108 (5.56%)  7/216 (3.24%) 
Pollakiuria * 1  6/107 (5.61%)  4/108 (3.70%)  6/108 (5.56%)  10/216 (4.63%) 
Urinary incontinence * 1  6/107 (5.61%)  6/108 (5.56%)  3/108 (2.78%)  9/216 (4.17%) 
Urinary retention * 1  6/107 (5.61%)  0/108 (0.00%)  2/108 (1.85%)  2/216 (0.93%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  4/107 (3.74%)  12/108 (11.11%)  12/108 (11.11%)  24/216 (11.11%) 
Dyspnoea * 1  3/107 (2.80%)  17/108 (15.74%)  18/108 (16.67%)  35/216 (16.20%) 
Epistaxis * 1  1/107 (0.93%)  7/108 (6.48%)  6/108 (5.56%)  13/216 (6.02%) 
Oropharyngeal pain * 1  4/107 (3.74%)  16/108 (14.81%)  14/108 (12.96%)  30/216 (13.89%) 
Skin and subcutaneous tissue disorders         
Alopecia * 1  1/107 (0.93%)  6/108 (5.56%)  7/108 (6.48%)  13/216 (6.02%) 
Erythema * 1  5/107 (4.67%)  10/108 (9.26%)  8/108 (7.41%)  18/216 (8.33%) 
Hypoaesthesia facial * 1  2/107 (1.87%)  6/108 (5.56%)  5/108 (4.63%)  11/216 (5.09%) 
Pruritus * 1  4/107 (3.74%)  36/108 (33.33%)  28/108 (25.93%)  64/216 (29.63%) 
Rash * 1  8/107 (7.48%)  78/108 (72.22%)  82/108 (75.93%)  160/216 (74.07%) 
Rash generalised * 1  0/107 (0.00%)  13/108 (12.04%)  7/108 (6.48%)  20/216 (9.26%) 
Rash pruritic * 1  0/107 (0.00%)  6/108 (5.56%)  4/108 (3.70%)  10/216 (4.63%) 
Urticaria * 1  3/107 (2.80%)  31/108 (28.70%)  38/108 (35.19%)  69/216 (31.94%) 
Vascular disorders         
Flushing * 1  6/107 (5.61%)  12/108 (11.11%)  8/108 (7.41%)  20/216 (9.26%) 
Hypertension * 1  8/107 (7.48%)  6/108 (5.56%)  3/108 (2.78%)  9/216 (4.17%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.1
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.
In multi-site studies, PI can publish after sponsor publishes or 18 months after study completion. PI gives sponsor a draft 60 days before publication. Sponsor can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Publications of Results:
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00050778     History of Changes
Other Study ID Numbers: CAMMS223
First Submitted: December 19, 2002
First Posted: December 23, 2002
Results First Submitted: November 3, 2008
Results First Posted: August 25, 2009
Last Update Posted: January 8, 2015