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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00930553




Registration number
NCT00930553
Ethics application status
Date submitted
26/06/2009
Date registered
26/06/2009
Date last updated
2/05/2017

Titles & IDs
Public title
An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
Scientific title
An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
Secondary ID [1] 0 0
2009-010788-18
Secondary ID [2] 0 0
CAMMS03409
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Relapsing-Remitting 0 0
Multiple Sclerosis, Relapsing-Remitting 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - alemtuzumab
Other interventions - alemtuzumab

Experimental: Previously treated with alemtuzumab - Alemtuzumab 12 mg per day administered through IV, once a day for 3 consecutive days (participants might receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period)

Experimental: Previously treated with interferon beta-1a (Rebif®) - Alemtuzumab 12 mg per day administered through IV, once a day for 5 consecutive days during the first cycle and 12 mg per day administered through IV, once a day for 3 consecutive days during the second cycle, 12 months later. Participants might qualify for as-needed retreatment (12 mg per day administered through IV, once a day for 3 consecutive days) after their second fixed annual cycle.

Experimental: Previously treated with alemtuzumab - Alemtuzumab 12 mg per day administered through IV, once a day for 3 consecutive days (participants might receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period)

Experimental: Previously treated with interferon beta-1a (Rebif®) - Alemtuzumab 12 mg per day administered through IV, once a day for 5 consecutive days during the first cycle and 12 mg per day administered through IV, once a day for 3 consecutive days during the second cycle, 12 months later. Participants might qualify for as-needed retreatment (12 mg per day administered through IV, once a day for 3 consecutive days) after their second fixed annual cycle.


Other interventions: alemtuzumab
Alemtuzumab 12 mg/day IV infusion on 5 consecutive days if the participants had no prior alemtuzumab exposure (ie, first treatment course). All subsequent treatment courses were for 3 days only.

Other interventions: alemtuzumab
Alemtuzumab 12 mg/day IV infusion on 5 consecutive days if the participants had no prior alemtuzumab exposure (ie, first treatment course). All subsequent treatment courses were for 3 days only.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Relapse Rate (ARR) - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.
Timepoint [1] 0 0
Year 3, 4, 5, 6 from the Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively)
Primary outcome [2] 0 0
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [2] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Primary outcome [3] 0 0
Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.
Timepoint [3] 0 0
Year 1 prior to retreatment, Year 1, 2, 3 after retreatment
Primary outcome [4] 0 0
Number of Participants With Sustained Accumulation of Disability (SAD) - SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. 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) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.
Timepoint [4] 0 0
Baseline (Year 0) up to Year 6
Primary outcome [5] 0 0
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison - SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. 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) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [5] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Primary outcome [6] 0 0
Annualized Relapse Rate (ARR) - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.
Timepoint [6] 0 0
Year 3, 4, 5, 6 from the Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively)
Primary outcome [7] 0 0
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [7] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Primary outcome [8] 0 0
Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.
Timepoint [8] 0 0
Year 1 prior to retreatment, Year 1, 2, 3 after retreatment
Primary outcome [9] 0 0
Number of Participants With Sustained Accumulation of Disability (SAD) - SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. 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) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.
Timepoint [9] 0 0
Baseline (Year 0) up to Year 6
Primary outcome [10] 0 0
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison - SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. 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) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [10] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [1] 0 0
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6 - SRD was defined as a =1 point decrease in EDSS score lasting >= 6 months. SRD is only applicable to participants with a baseline EDSS score of >= 2.0. 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 ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.
Timepoint [1] 0 0
Baseline (Year 0) up to Year 6
Secondary outcome [2] 0 0
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study - SRD was defined as a >=1 point decrease in EDSS score lasting >=6 months. SRD is only applicable to participants with a baseline EDSS score of =2.0. 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 ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [2] 0 0
Extension study (CAMMS03409) baseline up to Extension Year 2
Secondary outcome [3] 0 0
Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6 - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 [NCT00530348] or CAMMS324 [NCT00548405]) value from EDSS scores at specified time points.
Timepoint [3] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [4] 0 0
Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.
Timepoint [4] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [5] 0 0
Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
Timepoint [5] 0 0
Retreatment baseline, Year 1, 2 and 3 after retreatment baseline
Secondary outcome [6] 0 0
Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.
Timepoint [6] 0 0
Year 3, 4, 5 and 6
Secondary outcome [7] 0 0
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [7] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [8] 0 0
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.
Timepoint [8] 0 0
Retreatment Baseline, Year 1, 2 and 3 after retreatment
Secondary outcome [9] 0 0
Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6 - Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.
Timepoint [9] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [10] 0 0
Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity - Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.
Timepoint [10] 0 0
Year 3, 4, 5 and 6
Secondary outcome [11] 0 0
Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6 - Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.
Timepoint [11] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [12] 0 0
Percentage of Relapse Free Participants - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.
Timepoint [12] 0 0
Year 3, 4, 5 and 6
Secondary outcome [13] 0 0
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6 - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Timepoint [13] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension group", "alemtuzumab Treatment CAMMS324 Extension" group, respectively),Year 3, 4, 5 and 6
Secondary outcome [14] 0 0
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Timepoint [14] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [15] 0 0
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6 - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Timepoint [15] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [16] 0 0
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Timepoint [16] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [17] 0 0
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6 - FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.
Timepoint [17] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [18] 0 0
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison - FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [18] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [19] 0 0
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6 - EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.
Timepoint [19] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [20] 0 0
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison - EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [20] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [21] 0 0
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6 - SRD was defined as a =1 point decrease in EDSS score lasting >= 6 months. SRD is only applicable to participants with a baseline EDSS score of >= 2.0. 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 ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.
Timepoint [21] 0 0
Baseline (Year 0) up to Year 6
Secondary outcome [22] 0 0
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study - SRD was defined as a >=1 point decrease in EDSS score lasting >=6 months. SRD is only applicable to participants with a baseline EDSS score of =2.0. 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 ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [22] 0 0
Extension study (CAMMS03409) baseline up to Extension Year 2
Secondary outcome [23] 0 0
Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6 - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 [NCT00530348] or CAMMS324 [NCT00548405]) value from EDSS scores at specified time points.
Timepoint [23] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [24] 0 0
Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.
Timepoint [24] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [25] 0 0
Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment - 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), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
Timepoint [25] 0 0
Retreatment baseline, Year 1, 2 and 3 after retreatment baseline
Secondary outcome [26] 0 0
Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.
Timepoint [26] 0 0
Year 3, 4, 5 and 6
Secondary outcome [27] 0 0
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [27] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [28] 0 0
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment - Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.
Timepoint [28] 0 0
Retreatment Baseline, Year 1, 2 and 3 after retreatment
Secondary outcome [29] 0 0
Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6 - Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.
Timepoint [29] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [30] 0 0
Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity - Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.
Timepoint [30] 0 0
Year 3, 4, 5 and 6
Secondary outcome [31] 0 0
Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6 - Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.
Timepoint [31] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [32] 0 0
Percentage of Relapse Free Participants - Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.
Timepoint [32] 0 0
Year 3, 4, 5 and 6
Secondary outcome [33] 0 0
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6 - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Timepoint [33] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension group", "alemtuzumab Treatment CAMMS324 Extension" group, respectively),Year 3, 4, 5 and 6
Secondary outcome [34] 0 0
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Timepoint [34] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [35] 0 0
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6 - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
Timepoint [35] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [36] 0 0
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison - SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
Timepoint [36] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [37] 0 0
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6 - FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.
Timepoint [37] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6
Secondary outcome [38] 0 0
Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison - FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [38] 0 0
Baseline (Year 0 of initial studies) up to Year 4
Secondary outcome [39] 0 0
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6 - EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.
Timepoint [39] 0 0
Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6
Secondary outcome [40] 0 0
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison - EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
Timepoint [40] 0 0
Baseline (Year 0 of initial studies) up to Year 4

Eligibility
Key inclusion criteria
- 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and
had not subsequently received disease modifying treatments (other than glatiramer
acetate or interferon beta); or

- 2.Received Rebif® in CAMMS323 or CAMMS324, completed the 2-year study period, and had
not subsequently received alternative disease modifying treatments (other than
glatiramer acetate or another interferon beta); or

- 3.Participated in CAMMS223.

- NOTE: Criteria 1 and 2 above meant that participants who enrolled in CAMMS323 or
CAMMS324 but did not complete the 2-year study period or went on to receive non-study
drug DMTs after randomization were not eligible for inclusion in the Extension Study.
Participants who enrolled in CAMMS324 after participation in CAMMS223 must meet
criteria 1 or 2 to be eligible for inclusion in the Extension Study.
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any alemtuzumab participant from CAMMS223, CAMMS323, or CAMMS324 who had received
alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies), or
was participating in any other investigational study, unless approved by Genzyme. In
addition, these participants must be screened for disqualifying safety concerns before
receiving alemtuzumab retreatment.

- Any Rebif® participants from CAMMS223, CAMMS323, or CAMMS324 who met any of the
following criteria. In addition, these participants must be screened for disqualifying
safety concerns before receiving alemtuzumab treatment. a) Did not wish to receive
alemtuzumab; b) Ongoing participation in any other investigational study, unless
approved by Genzyme; c) Had received alemtuzumab off-label (ie, outside of one of the
prior Genzyme-sponsored studies); d) Known bleeding disorder or therapeutic
anticoagulation; e) Diagnosis of idiopathic thrombocytopenia purpura or other
autoimmune hematologic abnormality; f) History of malignancy, except basal cell skin
carcinoma; g) Intolerance of pulsed corticosteroids, especially a history of steroid
psychosis h) Significant Autoimmune disorder (other than MS); i) Major psychiatric
disorder or epileptic seizures not adequately controlled by treatment; j) Active
infection or high risk for infection k) Unwilling to use a reliable and acceptable
contraceptive method during and for at least 6 months following each alemtuzumab
treatment cycle (fertile participants only).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Southern Neurology - Kogarah
Recruitment hospital [3] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Gold Coast Hospital - Southport
Recruitment hospital [6] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [8] 0 0
Austin Health - Heidelberg
Recruitment hospital [9] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [10] 0 0
The Wesley Research Institute - Auchenflower QLD
Recruitment hospital [11] 0 0
The Queen Elizabeth Hospital - Woodville, SA
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Kogarah
Recruitment postcode(s) [3] 0 0
- Liverpool
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Southport
Recruitment postcode(s) [6] 0 0
- Hobart
Recruitment postcode(s) [7] 0 0
- Fitzroy
Recruitment postcode(s) [8] 0 0
- Heidelberg
Recruitment postcode(s) [9] 0 0
- Parkville
Recruitment postcode(s) [10] 0 0
- Auchenflower QLD
Recruitment postcode(s) [11] 0 0
- Woodville, SA
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nevada
Country [19] 0 0
United States of America
State/province [19] 0 0
New Hampshire
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New Mexico
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Oklahoma
Country [26] 0 0
United States of America
State/province [26] 0 0
Pennsylvania
Country [27] 0 0
United States of America
State/province [27] 0 0
Rhode Island
Country [28] 0 0
United States of America
State/province [28] 0 0
Tennessee
Country [29] 0 0
United States of America
State/province [29] 0 0
Texas
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Washington
Country [32] 0 0
Argentina
State/province [32] 0 0
Buenos Aires
Country [33] 0 0
Austria
State/province [33] 0 0
Vienna
Country [34] 0 0
Belgium
State/province [34] 0 0
Brussel
Country [35] 0 0
Belgium
State/province [35] 0 0
Esneux
Country [36] 0 0
Belgium
State/province [36] 0 0
Leuven
Country [37] 0 0
Brazil
State/province [37] 0 0
Porto Alegre
Country [38] 0 0
Brazil
State/province [38] 0 0
Recife, PE
Country [39] 0 0
Brazil
State/province [39] 0 0
São Paulo, SP
Country [40] 0 0
Brazil
State/province [40] 0 0
São Paulo,SP
Country [41] 0 0
Canada
State/province [41] 0 0
Alberta
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Canada
State/province [43] 0 0
Quebec
Country [44] 0 0
Canada
State/province [44] 0 0
London, ON
Country [45] 0 0
Canada
State/province [45] 0 0
Ottawa, Ontario
Country [46] 0 0
Canada
State/province [46] 0 0
Vancouver, BC
Country [47] 0 0
Croatia
State/province [47] 0 0
Osijek
Country [48] 0 0
Croatia
State/province [48] 0 0
Rijeka
Country [49] 0 0
Croatia
State/province [49] 0 0
Varazdin
Country [50] 0 0
Croatia
State/province [50] 0 0
Zagreb
Country [51] 0 0
Czechia
State/province [51] 0 0
Brno
Country [52] 0 0
Czechia
State/province [52] 0 0
Hradec Kralove
Country [53] 0 0
Czechia
State/province [53] 0 0
Prague
Country [54] 0 0
Czechia
State/province [54] 0 0
Teplice
Country [55] 0 0
Denmark
State/province [55] 0 0
Copenhagen
Country [56] 0 0
Denmark
State/province [56] 0 0
Århus C
Country [57] 0 0
France
State/province [57] 0 0
Dijon Cedex
Country [58] 0 0
France
State/province [58] 0 0
Paris Cedex 13
Country [59] 0 0
France
State/province [59] 0 0
Rennes Cedex 9
Country [60] 0 0
France
State/province [60] 0 0
Strasbourg Cedex
Country [61] 0 0
France
State/province [61] 0 0
Toulouse Cedex 9
Country [62] 0 0
Germany
State/province [62] 0 0
DE
Country [63] 0 0
Germany
State/province [63] 0 0
Berlin-Mitte
Country [64] 0 0
Germany
State/province [64] 0 0
Dresden
Country [65] 0 0
Germany
State/province [65] 0 0
Frankfurt am Main
Country [66] 0 0
Germany
State/province [66] 0 0
Hamburg
Country [67] 0 0
Germany
State/province [67] 0 0
Hannover
Country [68] 0 0
Germany
State/province [68] 0 0
Hennigsdorf
Country [69] 0 0
Germany
State/province [69] 0 0
Ingolstadt
Country [70] 0 0
Germany
State/province [70] 0 0
München
Country [71] 0 0
Germany
State/province [71] 0 0
Rostock
Country [72] 0 0
Germany
State/province [72] 0 0
Ulm
Country [73] 0 0
Germany
State/province [73] 0 0
Wermsdorf
Country [74] 0 0
Israel
State/province [74] 0 0
Ein Karem, Jerusalem
Country [75] 0 0
Israel
State/province [75] 0 0
Ramat Gan
Country [76] 0 0
Israel
State/province [76] 0 0
Tel Aviv
Country [77] 0 0
Italy
State/province [77] 0 0
Cagliari
Country [78] 0 0
Italy
State/province [78] 0 0
Gallarate (Varese)
Country [79] 0 0
Italy
State/province [79] 0 0
Orbassano (TO)
Country [80] 0 0
Italy
State/province [80] 0 0
Roma
Country [81] 0 0
Mexico
State/province [81] 0 0
Chihuahua, CHH
Country [82] 0 0
Mexico
State/province [82] 0 0
Mexico City, DFE
Country [83] 0 0
Netherlands
State/province [83] 0 0
Den Bosch
Country [84] 0 0
Netherlands
State/province [84] 0 0
Sittard-Geleen
Country [85] 0 0
Poland
State/province [85] 0 0
Krakow
Country [86] 0 0
Poland
State/province [86] 0 0
Lodz
Country [87] 0 0
Poland
State/province [87] 0 0
Lublin
Country [88] 0 0
Poland
State/province [88] 0 0
Poznan
Country [89] 0 0
Poland
State/province [89] 0 0
Warsaw
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Kazan
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Moscow
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Nizhny Novgorod
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Novosibirsk
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Pyatigorsk
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Samara
Country [96] 0 0
Russian Federation
State/province [96] 0 0
St. Petersburg
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Ufa
Country [98] 0 0
Serbia
State/province [98] 0 0
Belgrade
Country [99] 0 0
Serbia
State/province [99] 0 0
Kragujevac
Country [100] 0 0
Serbia
State/province [100] 0 0
Nis
Country [101] 0 0
Serbia
State/province [101] 0 0
Novi Sad
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
Madrid
Country [104] 0 0
Spain
State/province [104] 0 0
Málaga
Country [105] 0 0
Spain
State/province [105] 0 0
Seville
Country [106] 0 0
Sweden
State/province [106] 0 0
Göteborg
Country [107] 0 0
Sweden
State/province [107] 0 0
Umeå
Country [108] 0 0
Ukraine
State/province [108] 0 0
Kharkov
Country [109] 0 0
Ukraine
State/province [109] 0 0
Kiev-21
Country [110] 0 0
Ukraine
State/province [110] 0 0
Kiev
Country [111] 0 0
Ukraine
State/province [111] 0 0
Lviv
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Bristol
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Cambridge
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Cardiff
Country [115] 0 0
United Kingdom
State/province [115] 0 0
London
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Salford
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genzyme, a Sanofi Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Bayer
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This open-label, rater-blinded extension study enrolled participants who had
relapsing-remitting multiple sclerosis (RRMS) and who participated in one of three prior
Genzyme-sponsored studies of alemtuzumab (CAMMS223 [NCT00050778], CAMMS323 [NCT00530348] also
known as CARE-MS I, or CAMMS324 [NCT00548405] also known as CARE-MS II). The purposes of this
study were:

1. To examine the long term safety and efficacy of alemtuzumab treatment in participants
who received alemtuzumab as their study treatment in one of the prior studies.

2. To examine the safety and efficacy of initial alemtuzumab treatment in this study for
participants who received Rebif® (interferon beta-1a) as their study treatment in one of
the prior studies.

3. To determine the safety and efficacy of additional "as needed" alemtuzumab treatment
courses. This applied both to participants who received alemtuzumab for the first time
in one of the prior studies or for the first time in this extension study.
Trial website
https://clinicaltrials.gov/show/NCT00930553
Trial related presentations / publications
CAMMS223 Trial Investigators, Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
CAMMS223 Trial Investigators, Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
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