An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab

• ClinicalTrials.gov Identifier: NCT00930553
• Recruitment Status: Completed
• First Posted: June 30, 2009
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017
• Sponsor: Genzyme, a Sanofi Company
• Collaborator: Bayer
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis, Relapsing-Remitting
• Intervention: Biological: alemtuzumab
• Enrollment: 1314

Participant Flow

Recruitment Details	This extension study enrolled participants from previous 3 studies: CAMMS223 (NCT00050778), CAMMS323 (NCT00530348), and CAMMS324 (NCT00548405). Participants were enrolled in this study only after their Month 24 visit in CAMMS323 and CAMMS324. CAMMS223 participants were enrolled within 6 months once their site received approval of extension study.
Pre-assignment Details	Efficacy outcome data was analyzed only on CAMMS323 and CAMMS324 participants; safety data was analyzed on all participants, as pre-specified in protocol.

Arm/Group Title	Alemtuzumab
Arm/Group Description	Participants enrolled from any of the prior studies received long-term follow-up in this study. Participants randomized to receive interferon beta-1a (IFNB-1a) in prior studies received alemtuzumab 12 mg/day infusion intravenously (IV) once daily (QD) for 5 consecutive days in treatment Course 1, and for 3 consecutive days in treatment Course 2, 12 months later in this study. Participants who received 2 treatment courses with alemtuzumab could be treated with additional alemtuzumab courses of 12 mg/day infusion IV QD, for 3 consecutive days at least 48 weeks after the prior course if they had documented evidence of resumed disease activity (defined as >=1 protocol-defined relapse and/or >=2 new or enlarging brain or spinal lesions on magnetic resonance imaging [MRI]), unless they met safety-related retreatment disqualifying criteria.
Period Title: Overall Study
Started	1314
Participants Entered From CAMMS223	141
Participants Entered From CAMMS323	488
Participants Entered From CAMMS324	685
Completed	1091
Not Completed	223
Reason Not Completed
Adverse Event	1
Lack of Efficacy	7
Physician Decision	39
Protocol Violation	1
Pregnancy	1
Withdrawal by Subject	88
Lost to Follow-up	25
Death	9
Study terminated by sponsor	24
Other than specified above	28

Baseline Characteristics

Arm/Group Title		Alemtuzumab
Arm/Group Description		Participants enrolled from any of the previous studies received long-term follow-up in this study. Participants randomized to receive IFNB-1a in any of the previous studies received alemtuzumab 12 mg/day infusion IV, QD for 5 consecutive days in treatment Course 1, and for 3 consecutive days in treatment Course 2, 12 months later in this study. Participants who received 2 treatment courses with alemtuzumab could be treated with additional alemtuzumab courses of 12 mg/day infusion IV QD, for 3 consecutive days at least 48 weeks after the prior course if they had documented evidence of resumed disease activity (defined as >=1 protocol-defined relapse and/or >=2 new or enlarging brain or spinal lesions on MRI), unless they met safety-related retreatment disqualifying criteria.
Overall Number of Baseline Participants		1314
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1314 participants
		36.7 (8.51)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1314 participants
	Female	857 65.2%
	Male	457 34.8%

Outcome Measures

1. Primary Outcome

Title	Annualized Relapse Rate (ARR)
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 (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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in this extension study (CAMMS03409).	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in this extension study (CAMMS03409).
Overall Number of Participants Analyzed	353	391
Measure Type: Number; Unit of Measure: relapses per participant per year
Year 3	0.19	0.22
Year 4	0.16	0.24
Year 5	0.15	0.19
Year 6	0.12	0.16

2. Primary Outcome

Title	Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323, were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324, were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: relapses per participant per year
	0.42; (0.28 to 0.64)	0.14; (0.09 to 0.21)	0.60; (0.45 to 0.78)	0.15; (0.10 to 0.22)

3. Primary Outcome

Title	Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment
Description	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.
Time Frame	Year 1 prior to retreatment, Year 1, 2, 3 after retreatment

Outcome Measure Data

Analysis Population Description

Subset of FAS included participants who had received alemtuzumab in CAMMS323 or CAMMS324 and received an additional course of alemtuzumab in this extension study.

Arm/Group Title	Alemtuzumab Retreatment
Arm/Group Description:	Participants who received alemtuzumab in CAMMS323 (NCT00530348) or CAMMS324 (NCT00548405), received an additional course of alemtuzumab in this study.
Overall Number of Participants Analyzed	321
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: relapses per participant per year
Year 1 prior to retreatment	0.79; (0.73 to 0.87)
Year 1 after retreatment	0.18; (0.14 to 0.24)
Year 2 after retreatment	0.29; (0.23 to 0.38)
Year 3 after retreatment	0.30; (0.21 to 0.41)

4. Primary Outcome

Title	Number of Participants With Sustained Accumulation of Disability (SAD)
Description	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.
Time Frame	Baseline (Year 0) up to Year 6

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in this extension study.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in this extension study.
Overall Number of Participants Analyzed	376	426
Measure Type: Count of Participants; Unit of Measure: Participants
	79	118

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alemtuzumab Treatment CAMMS323 Extension
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	22.33
	Confidence Interval	(2-Sided) 95%; 18.33 to 27.06
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alemtuzumab Treatment CAMMS324 Extension
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	29.69
	Confidence Interval	(2-Sided) 95%; 25.42 to 34.49
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

5. Primary Outcome

Title	Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Measure Type: Count of Participants; Unit of Measure: Participants
	13	11	29	17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	9.35
	Confidence Interval	(2-Sided) 95%; 5.54 to 15.56
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	7.95
	Confidence Interval	(2-Sided) 95%; 4.48 to 13.90
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	20.42
	Confidence Interval	(2-Sided) 95%; 14.67 to 28.03
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SAD
	Estimated Value	11.99
	Confidence Interval	(2-Sided) 95%; 7.63 to 18.58
	Estimation Comments	The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.

6. Secondary Outcome

Title	Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6
Description	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.
Time Frame	Baseline (Year 0) up to Year 6

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in this extension study.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in this extension study.
Overall Number of Participants Analyzed	235	321
Measure Type: Count of Participants; Unit of Measure: Participants
	74	130

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alemtuzumab Treatment CAMMS323 Extension
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SRD
	Estimated Value	32.69
	Confidence Interval	(2-Sided) 95%; 26.96 to 39.28
	Estimation Comments	The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alemtuzumab Treatment CAMMS324 Extension
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SRD
	Estimated Value	42.46
	Confidence Interval	(2-Sided) 95%; 37.08 to 48.28
	Estimation Comments	The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.

7. Secondary Outcome

Title	Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study
Description	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.
Time Frame	Extension study (CAMMS03409) baseline up to Extension Year 2

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	65	102
Measure Type: Count of Participants; Unit of Measure: Participants
	11	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SRD
	Estimated Value	16.92
	Confidence Interval	(2-Sided) 95%; 9.75 to 28.47
	Estimation Comments	The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Percentage with SRD
	Estimated Value	13.89
	Confidence Interval	(2-Sided) 95%; 8.47 to 22.33
	Estimation Comments	The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.

8. Secondary Outcome

Title	Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6
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), 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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	326	370
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 3	-0.08; (-0.20 to 0.04)	-0.02; (-0.14 to 0.10)
Change at Year 4	-0.06; (-0.19 to 0.07)	0.06; (-0.07 to 0.19)
Change at Year 5	0.06; (-0.08 to 0.19)	0.13; (-0.01 to 0.27)
Change at Year 6	0.09; (-0.04 to 0.23)	0.18; (0.03 to 0.32)

9. Secondary Outcome

Title	Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison
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), 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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323, were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324, were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324, were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Year 0 - 2	-0.15; (-0.32 to 0.03)	-0.07; (-0.23 to 0.09)	0.11; (-0.05 to 0.26)	-0.02; (-0.18 to 0.14)
Year 3 - 4	-0.21; (-0.43 to 0.00)	0.08; (-0.11 to 0.27)	0.20; (-0.01 to 0.41)	0.13; (-0.05 to 0.31)

10. Secondary Outcome

Title	Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment
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), 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.
Time Frame	Retreatment baseline, Year 1, 2 and 3 after retreatment baseline

Outcome Measure Data

Analysis Population Description

Subset of FAS included participants who had received alemtuzumab in CAMMS323 or CAMMS324 and received an additional course of alemtuzumab in this extension study.

Arm/Group Title		Alemtuzumab Retreatment
Arm/Group Description:		Participants who received alemtuzumab in CAMMS323 or CAMMS324 who received an additional course of alemtuzumab in CAMMS03409.
Overall Number of Participants Analyzed		321
Mean (Standard Deviation); Unit of Measure: units on a scale
Retreatment baseline	Number Analyzed	307 participants
		2.89 (1.514)
Change at Year 1 after retreatment baseline	Number Analyzed	256 participants
		-0.22 (1.033)
Change at Year 2 after retreatment baseline	Number Analyzed	158 participants
		-0.13 (1.109)
Change at Year 3 after retreatment baseline	Number Analyzed	75 participants
		0.07 (1.356)

11. Secondary Outcome

Title	Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity
Description	Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.
Time Frame	Year 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title		Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:		Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed		328	356
Measure Type: Number; Unit of Measure: percentage of participants
Year 3	Number Analyzed	328 participants	356 participants
		72.6	68.8
Year 4	Number Analyzed	323 participants	332 participants
		70.3	70.2
Year 5	Number Analyzed	319 participants	321 participants
		70.2	67.0
Year 6	Number Analyzed	307 participants	312 participants
		66.8	69.6

12. Secondary Outcome

Title	Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title		IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:		Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed		139	139	143	143
Measure Type: Number; Unit of Measure: percentage of participants
Year 0 - 1	Number Analyzed	135 participants	135 participants	139 participants	138 participants
		57	79.3	44.6	63.8
Year 0 - 2	Number Analyzed	135 participants	132 participants	139 participants	131 participants
		60.7	81.8	47.5	81.7

13. Secondary Outcome

Title	Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment
Description	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.
Time Frame	Retreatment Baseline, Year 1, 2 and 3 after retreatment

Outcome Measure Data

Analysis Population Description

Subset of FAS included participants who had received alemtuzumab in CAMMS323 or CAMMS324 and received an additional course of alemtuzumab in this extension study.

Arm/Group Title		Alemtuzumab Retreatment
Arm/Group Description:		Participants who received alemtuzumab in CAMMS323 or CAMMS324 who received an additional course of alemtuzumab in CAMMS03409.
Overall Number of Participants Analyzed		321
Measure Type: Number; Unit of Measure: percentage of participants
Retreatment baseline	Number Analyzed	315 participants
		49.2
Year 1 after retreatment baseline	Number Analyzed	301 participants
		64.1
Year 2 after retreatment baseline	Number Analyzed	197 participants
		66.0
Year 3 after retreatment baseline	Number Analyzed	113 participants
		60.2

14. Secondary Outcome

Title	Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6
Description	Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title		Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:		Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed		332	364
Mean (Standard Deviation); Unit of Measure: percent change
Change at Year 3	Number Analyzed	332 participants	364 participants
		-6.57 (29.96)	1.69 (31.62)
Change at Year 4	Number Analyzed	327 participants	339 participants
		-5.04 (32.88)	4.97 (41.11)
Change at Year 5	Number Analyzed	324 participants	336 participants
		-4.09 (36.99)	12.37 (80.74)
Change at Year 6	Number Analyzed	309 participants	319 participants
		-2.68 (42.92)	11.46 (73.91)

15. Secondary Outcome

Title	Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity
Description	Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.
Time Frame	Year 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title		Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:		Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed		330	356
Measure Type: Number; Unit of Measure: percentage of participants
Year 3	Number Analyzed	330 participants	356 participants
		90.6	86.5
Year 4	Number Analyzed	325 participants	331 participants
		87.1	88.8
Year 5	Number Analyzed	321 participants	321 participants
		87.5	89.4
Year 6	Number Analyzed	308 participants	310 participants
		86.7	90.0

16. Secondary Outcome

Title	Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6
Description	Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title		Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:		Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed		325	355
Mean (Standard Deviation); Unit of Measure: percent change
Change at Year 3	Number Analyzed	325 participants	355 participants
		-1.068 (1.185)	-0.761 (1.240)
Change at Year 4	Number Analyzed	323 participants	331 participants
		-1.251 (1.228)	-0.949 (1.341)
Change at Year 5	Number Analyzed	321 participants	317 participants
		-1.437 (1.317)	-0.983 (1.374)
Change at Year 6	Number Analyzed	308 participants	315 participants
		-1.601 (1.370)	-1.051 (1.472)

17. Secondary Outcome

Title	Percentage of Relapse Free Participants
Description	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.
Time Frame	Year 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	353	391
Measure Type: Number; Unit of Measure: percentage of participants
Year 3	84.14	80.56
Year 4	86.84	79.27
Year 5	87.35	83.29
Year 6	88.96	86.86

18. Secondary Outcome

Title	Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	340	375
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 3	1.90; (0.85 to 2.95)	1.72; (0.84 to 2.60)
Change at Year 4	2.15; (1.10 to 3.20)	1.34; (0.40 to 2.28)
Change at Year 5	1.85; (0.75 to 2.94)	1.34; (0.39 to 2.29)
Change at Year 6	1.65; (0.56 to 2.74)	1.00; (-0.03 to 2.03)

19. Secondary Outcome

Title	Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Year 1	1.16; (-0.48 to 2.81)	2.00; (0.43 to 3.57)	0.79; (-0.34 to 1.93)	1.56; (0.38 to 2.75)
Year 2	1.20; (-0.54 to 2.95)	0.41; (-1.21 to 2.04)	0.45; (-0.86 to 1.76)	1.31; (0.14 to 2.48)

20. Secondary Outcome

Title	Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	340	375
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 3	2.43; (1.07 to 3.78)	1.96; (0.85 to 3.07)
Change at Year 4	3.17; (1.85 to 4.49)	1.91; (0.77 to 3.05)
Change at Year 5	2.54; (1.23 to 3.85)	1.75; (0.59 to 2.92)
Change at Year 6	2.41; (1.01 to 3.80)	1.58; (0.35 to 2.82)

21. Secondary Outcome

Title	Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 1	2.88; (0.49 to 5.27)	1.98; (-0.46 to 4.43)	1.83; (0.30 to 3.36)	1.21; (-0.31 to 2.74)
Change at Year 2	2.32; (-0.11 to 4.74)	2.08; (-0.38 to 4.54)	1.65; (0.05 to 3.25)	1.65; (-0.01 to 3.31)

22. Secondary Outcome

Title	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
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	340	372
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 3	5.28; (2.03 to 8.52)	4.55; (1.89 to 7.21)
Change at Year 4	6.81; (3.55 to 10.08)	3.65; (0.98 to 6.32)
Change at Year 5	4.82; (1.55 to 8.10)	3.57; (0.78 to 6.37)
Change at Year 6	4.40; (1.03 to 7.78)	3.16; (0.07 to 6.25)

23. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 1	4.27; (-1.17 to 9.72)	4.82; (0.10 to 9.53)	3.19; (-0.12 to 6.51)	5.83; (2.74 to 8.92)
Change at Year 2	1.88; (-3.63 to 7.38)	3.10; (-2.16 to 8.35)	0.93; (-2.86 to 4.71)	4.66; (1.07 to 8.24)

24. Secondary Outcome

Title	Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Subset of full analysis set (FAS - defined as all participants randomized in CAMMS223, CAMMS323, and CAMMS324 and who received at least 1 dose of study drug) included participants who had received at least 1 dose of alemtuzumab in CAMMS323 and CAMMS324. Number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Alemtuzumab Treatment CAMMS323 Extension	Alemtuzumab Treatment CAMMS324 Extension
Arm/Group Description:	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS323 (NCT00530348) and enrolled in extension study CAMMS03409.	Participants who were randomized to alemtuzumab 12 mg/day treatment in CAMMS324 (NCT00548405) and enrolled in extension study CAMMS03409.
Overall Number of Participants Analyzed	337	374
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 3	3.505; (1.438 to 5.572)	2.859; (1.008 to 4.710)
Change at Year 4	5.144; (3.078 to 7.210)	2.992; (1.145 to 4.838)
Change at Year 5	4.409; (2.303 to 6.515)	3.034; (1.169 to 4.898)
Change at Year 6	4.134; (1.946 to 6.323)	3.155; (0.933 to 5.377)

25. Secondary Outcome

Title	Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison
Description	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.
Time Frame	Baseline (Year 0 of initial studies) up to Year 4

Outcome Measure Data

Analysis Population Description

Subset of FAS who received IFNB-1a in CAMMS323 or CAMMS324 and who were treated with alemtuzumab in CAMMS03409.

Arm/Group Title	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)	IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Arm/Group Description:	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS323 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. IFNB-1a treatment period	Participants who received IFNB-1a in CAMMS324 who were treated with alemtuzumab in CAMMS03409. Alemtuzumab treatment period
Overall Number of Participants Analyzed	139	139	143	143
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Change at Year 1	4.165; (0.639 to 7.691)	4.576; (1.419 to 7.733)	1.663; (-0.893 to 4.219)	4.337; (1.614 to 7.059)
Change at Year 2	2.359; (-1.319 to 6.037)	4.515; (1.407 to 7.622)	-0.712; (-3.552 to 2.129)	3.346; (0.324 to 6.368)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form in the extension study up to the end of extension study visit (up to Year 6) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs are treatment-emergent adverse events (TEAEs), AEs that developed/worsened during or at any time after first alemtuzumab treatment. Alemtuzumab TEAEs were defined as AEs with start dates and start times on or after the date and time of the first alemtuzumab treatment in CAMMS03409 or in prior studies (CAMMS223, CAMMS323, or CAMMS324).
Arm/Group Title	Alemtuzumab
Arm/Group Description	Participants enrolled in any of the previous studies who had received alemtuzumab. Participants enrolled in any of the previous studies who had received IFNB-1a, who received alemtuzumab 12 mg/day infusion in this study.
All-Cause Mortality
	Alemtuzumab
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Alemtuzumab
	Affected / at Risk (%)
Total	376/1314 (28.61%)
Blood and lymphatic system disorders
Acquired haemophilia † 1	1/1314 (0.08%)
Anaemia † 1	3/1314 (0.23%)
Autoimmune haemolytic anaemia † 1	1/1314 (0.08%)
Autoimmune pancytopenia † 1	1/1314 (0.08%)
Febrile neutropenia † 1	1/1314 (0.08%)
Haemolytic anaemia † 1	2/1314 (0.15%)
Haemorrhagic anaemia † 1	1/1314 (0.08%)
Immune thrombocytopenic purpura † 1	16/1314 (1.22%)
Lymphadenopathy † 1	1/1314 (0.08%)
Neutropenia † 1	1/1314 (0.08%)
Pancytopenia † 1	1/1314 (0.08%)
Thrombocytopenia † 1	1/1314 (0.08%)
Cardiac disorders
Acute myocardial infarction † 1	3/1314 (0.23%)
Angina pectoris † 1	4/1314 (0.30%)
Atrial fibrillation † 1	1/1314 (0.08%)
Bradycardia † 1	2/1314 (0.15%)
Bradycardia foetal † 1	1/1314 (0.08%)
Bradycardia neonatal † 1	1/1314 (0.08%)
Bundle branch block right † 1	1/1314 (0.08%)
Cardiac arrest † 1	1/1314 (0.08%)
Cardiac failure congestive † 1	2/1314 (0.15%)
Congestive cardiomyopathy † 1	1/1314 (0.08%)
Myocardial infarction † 1	2/1314 (0.15%)
Pericarditis † 1	1/1314 (0.08%)
Sinus bradycardia † 1	1/1314 (0.08%)
Tachycardia † 1	3/1314 (0.23%)
Congenital, familial and genetic disorders
Foetal cystic hygroma † 1	1/1314 (0.08%)
Ear and labyrinth disorders
Vertigo † 1	1/1314 (0.08%)
Endocrine disorders
Autoimmune hypothyroidism † 1	1/1314 (0.08%)
Autoimmune thyroiditis † 1	4/1314 (0.30%)
Basedow's disease † 1	39/1314 (2.97%)
Goitre † 1	3/1314 (0.23%)
Hyperparathyroidism † 1	1/1314 (0.08%)
Hyperthyroidism † 1	14/1314 (1.07%)
Hypothyroidism † 1	4/1314 (0.30%)
Eye disorders
Cataract † 1	1/1314 (0.08%)
Endocrine ophthalmopathy † 1	4/1314 (0.30%)
Glaucoma † 1	1/1314 (0.08%)
Iridocyclitis † 1	1/1314 (0.08%)
Optic atrophy † 1	1/1314 (0.08%)
Vision blurred † 1	1/1314 (0.08%)
Gastrointestinal disorders
Abdominal distension † 1	1/1314 (0.08%)
Abdominal hernia † 1	1/1314 (0.08%)
Abdominal pain † 1	11/1314 (0.84%)
Abdominal pain upper † 1	1/1314 (0.08%)
Ascites † 1	1/1314 (0.08%)
Colitis † 1	3/1314 (0.23%)
Colitis ischaemic † 1	1/1314 (0.08%)
Constipation † 1	1/1314 (0.08%)
Diarrhoea † 1	3/1314 (0.23%)
Duodenitis † 1	1/1314 (0.08%)
Enteritis † 1	1/1314 (0.08%)
Faecaloma † 1	1/1314 (0.08%)
Gastric ulcer haemorrhage † 1	1/1314 (0.08%)
Gastritis † 1	2/1314 (0.15%)
Impaired gastric emptying † 1	1/1314 (0.08%)
Inguinal hernia † 1	2/1314 (0.15%)
Nausea † 1	7/1314 (0.53%)
Oesophagitis † 1	1/1314 (0.08%)
Pancreatic fistula † 1	1/1314 (0.08%)
Pancreatic pseudocyst † 1	1/1314 (0.08%)
Pancreatitis † 1	1/1314 (0.08%)
Pancreatitis acute † 1	1/1314 (0.08%)
Peptic ulcer † 1	1/1314 (0.08%)
Small intestinal obstruction † 1	1/1314 (0.08%)
Upper gastrointestinal haemorrhage † 1	1/1314 (0.08%)
Vomiting † 1	6/1314 (0.46%)
General disorders
Catheter site pain † 1	1/1314 (0.08%)
Chest pain † 1	1/1314 (0.08%)
Chills † 1	1/1314 (0.08%)
Death † 1	1/1314 (0.08%)
Device dislocation † 1	1/1314 (0.08%)
Fatigue † 1	1/1314 (0.08%)
Inflammation † 1	1/1314 (0.08%)
Non-cardiac chest pain † 1	2/1314 (0.15%)
Perforated ulcer † 1	1/1314 (0.08%)
Pyrexia † 1	2/1314 (0.15%)
Hepatobiliary disorders
Biliary dyskinesia † 1	1/1314 (0.08%)
Cholangitis † 1	1/1314 (0.08%)
Cholecystitis † 1	4/1314 (0.30%)
Cholecystitis acute † 1	2/1314 (0.15%)
Cholelithiasis † 1	4/1314 (0.30%)
Hepatitis acute † 1	1/1314 (0.08%)
Sphincter of Oddi dysfunction † 1	1/1314 (0.08%)
Immune system disorders
Anaphylactoid reaction † 1	1/1314 (0.08%)
Drug hypersensitivity † 1	1/1314 (0.08%)
Hypersensitivity † 1	3/1314 (0.23%)
Infections and infestations
Abscess bacterial † 1	1/1314 (0.08%)
Abscess limb † 1	1/1314 (0.08%)
Appendicitis † 1	2/1314 (0.15%)
Appendicitis perforated † 1	1/1314 (0.08%)
Bone abscess † 1	1/1314 (0.08%)
Breast abscess † 1	1/1314 (0.08%)
Bronchitis † 1	1/1314 (0.08%)
Cellulitis † 1	6/1314 (0.46%)
Chronic hepatitis C † 1	1/1314 (0.08%)
Device related infection † 1	1/1314 (0.08%)
Diverticulitis † 1	2/1314 (0.15%)
Endometritis † 1	1/1314 (0.08%)
Escherichia urinary tract infection † 1	1/1314 (0.08%)
Furuncle † 1	1/1314 (0.08%)
Gastroenteritis † 1	7/1314 (0.53%)
Gastroenteritis bacterial † 1	1/1314 (0.08%)
Gastroenteritis viral † 1	2/1314 (0.15%)
HIV infection † 1	1/1314 (0.08%)
Helicobacter infection † 1	1/1314 (0.08%)
Herpes zoster † 1	10/1314 (0.76%)
Infection † 1	1/1314 (0.08%)
Infectious colitis † 1	1/1314 (0.08%)
Infective myositis † 1	1/1314 (0.08%)
Influenza † 1	2/1314 (0.15%)
Lower respiratory tract infection † 1	2/1314 (0.15%)
Lung abscess † 1	1/1314 (0.08%)
Oral herpes † 1	1/1314 (0.08%)
Pancreas infection † 1	1/1314 (0.08%)
Pneumonia † 1	13/1314 (0.99%)
Pneumonia fungal † 1	1/1314 (0.08%)
Pneumonia legionella † 1	1/1314 (0.08%)
Post procedural infection † 1	1/1314 (0.08%)
Pulmonary tuberculosis † 1	1/1314 (0.08%)
Pyelonephritis † 1	4/1314 (0.30%)
Pyelonephritis acute † 1	1/1314 (0.08%)
Respiratory tract infection viral † 1	2/1314 (0.15%)
Scrotal abscess † 1	1/1314 (0.08%)
Sepsis † 1	8/1314 (0.61%)
Soft tissue infection † 1	1/1314 (0.08%)
Staphylococcal abscess † 1	1/1314 (0.08%)
Subcutaneous abscess † 1	1/1314 (0.08%)
Tracheobronchitis † 1	1/1314 (0.08%)
Tubo-ovarian abscess † 1	1/1314 (0.08%)
Urinary tract infection † 1	7/1314 (0.53%)
Urosepsis † 1	1/1314 (0.08%)
Varicella zoster virus infection † 1	1/1314 (0.08%)
Viral infection † 1	1/1314 (0.08%)
Injury, poisoning and procedural complications
Accidental overdose † 1	1/1314 (0.08%)
Ankle fracture † 1	1/1314 (0.08%)
Cartilage injury † 1	1/1314 (0.08%)
Cervical vertebral fracture † 1	1/1314 (0.08%)
Concussion † 1	3/1314 (0.23%)
Contusion † 1	2/1314 (0.15%)
Femur fracture † 1	1/1314 (0.08%)
Fibula fracture † 1	2/1314 (0.15%)
Gastrostomy failure † 1	1/1314 (0.08%)
Hip fracture † 1	1/1314 (0.08%)
Humerus fracture † 1	1/1314 (0.08%)
Incision site oedema † 1	1/1314 (0.08%)
Intentional overdose † 1	2/1314 (0.15%)
Laceration † 1	2/1314 (0.15%)
Ligament sprain † 1	1/1314 (0.08%)
Lumbar vertebral fracture † 1	1/1314 (0.08%)
Meniscus injury † 1	1/1314 (0.08%)
Multiple fractures † 1	1/1314 (0.08%)
Overdose † 1	2/1314 (0.15%)
Pancreatic injury † 1	1/1314 (0.08%)
Pelvic fracture † 1	1/1314 (0.08%)
Post lumbar puncture syndrome † 1	1/1314 (0.08%)
Post procedural fistula † 1	1/1314 (0.08%)
Post procedural haematoma † 1	1/1314 (0.08%)
Procedural nausea † 1	1/1314 (0.08%)
Procedural pain † 1	1/1314 (0.08%)
Skull fractured base † 1	1/1314 (0.08%)
Spinal column injury † 1	1/1314 (0.08%)
Splenic rupture † 1	1/1314 (0.08%)
Subdural haematoma † 1	1/1314 (0.08%)
Tibia fracture † 1	2/1314 (0.15%)
Ulna fracture † 1	1/1314 (0.08%)
Wound † 1	1/1314 (0.08%)
Wound dehiscence † 1	1/1314 (0.08%)
Wrist fracture † 1	2/1314 (0.15%)
Investigations
Blood creatinine increased † 1	1/1314 (0.08%)
Urine ketone body present † 1	1/1314 (0.08%)
Metabolism and nutrition disorders
Dehydration † 1	6/1314 (0.46%)
Diabetic ketoacidosis † 1	1/1314 (0.08%)
Electrolyte imbalance † 1	1/1314 (0.08%)
Hyperglycaemia † 1	1/1314 (0.08%)
Hypocalcaemia † 1	2/1314 (0.15%)
Hypokalaemia † 1	2/1314 (0.15%)
Hypophosphataemia † 1	1/1314 (0.08%)
Malnutrition † 1	1/1314 (0.08%)
Obesity † 1	1/1314 (0.08%)
Type 1 diabetes mellitus † 1	1/1314 (0.08%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/1314 (0.15%)
Arthritis † 1	1/1314 (0.08%)
Back disorder † 1	1/1314 (0.08%)
Back pain † 1	2/1314 (0.15%)
Chondropathy † 1	1/1314 (0.08%)
Costochondritis † 1	2/1314 (0.15%)
Flank pain † 1	2/1314 (0.15%)
Haemarthrosis † 1	1/1314 (0.08%)
Joint effusion † 1	1/1314 (0.08%)
Joint instability † 1	1/1314 (0.08%)
Joint range of motion decreased † 1	1/1314 (0.08%)
Muscle spasms † 1	1/1314 (0.08%)
Muscular weakness † 1	2/1314 (0.15%)
Musculoskeletal chest pain † 1	2/1314 (0.15%)
Musculoskeletal stiffness † 1	1/1314 (0.08%)
Osteoarthritis † 1	2/1314 (0.15%)
Osteonecrosis † 1	2/1314 (0.15%)
Pain in jaw † 1	1/1314 (0.08%)
Plantar fasciitis † 1	1/1314 (0.08%)
Rotator cuff syndrome † 1	1/1314 (0.08%)
SAPHO syndrome † 1	1/1314 (0.08%)
Spinal pain † 1	1/1314 (0.08%)
Temporomandibular joint syndrome † 1	1/1314 (0.08%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts † 1	3/1314 (0.23%)
B-cell lymphoma † 1	1/1314 (0.08%)
Basal cell carcinoma † 1	1/1314 (0.08%)
Benign hydatidiform mole † 1	1/1314 (0.08%)
Benign neoplasm of thyroid gland † 1	2/1314 (0.15%)
Breast cancer † 1	2/1314 (0.15%)
Castleman's disease † 1	1/1314 (0.08%)
Cervix carcinoma stage II † 1	1/1314 (0.08%)
Insulinoma † 1	1/1314 (0.08%)
Invasive ductal breast carcinoma † 1	1/1314 (0.08%)
Invasive lobular breast carcinoma † 1	1/1314 (0.08%)
Malignant melanoma † 1	1/1314 (0.08%)
Malignant melanoma in situ † 1	1/1314 (0.08%)
Meningioma benign † 1	1/1314 (0.08%)
Metastatic malignant melanoma † 1	1/1314 (0.08%)
Neoplasm skin † 1	1/1314 (0.08%)
Non-small cell lung cancer † 1	1/1314 (0.08%)
Ovarian adenoma † 1	1/1314 (0.08%)
Pancreatic neuroendocrine tumour † 1	1/1314 (0.08%)
Papillary thyroid cancer † 1	3/1314 (0.23%)
Parathyroid tumour benign † 1	1/1314 (0.08%)
Pituitary tumour † 1	1/1314 (0.08%)
Squamous cell carcinoma † 1	1/1314 (0.08%)
Thyroid cancer † 1	1/1314 (0.08%)
Uterine leiomyoma † 1	5/1314 (0.38%)
Vulval cancer stage 0 † 1	1/1314 (0.08%)
Nervous system disorders
Altered state of consciousness † 1	1/1314 (0.08%)
Basal ganglia haemorrhage † 1	1/1314 (0.08%)
Cerebral haemorrhage † 1	2/1314 (0.15%)
Complex partial seizures † 1	1/1314 (0.08%)
Depressed level of consciousness † 1	1/1314 (0.08%)
Dizziness † 1	2/1314 (0.15%)
Dysarthria † 1	1/1314 (0.08%)
Embolic stroke † 1	1/1314 (0.08%)
Headache † 1	7/1314 (0.53%)
Intracranial aneurysm † 1	1/1314 (0.08%)
Intraventricular haemorrhage † 1	1/1314 (0.08%)
Loss of consciousness † 1	2/1314 (0.15%)
Migraine † 1	1/1314 (0.08%)
Multiple sclerosis † 1	4/1314 (0.30%)
Multiple sclerosis relapse † 1	67/1314 (5.10%)
Optic neuritis † 1	1/1314 (0.08%)
Seizure † 1	4/1314 (0.30%)
Status epilepticus † 1	1/1314 (0.08%)
Syncope † 1	9/1314 (0.68%)
Tension headache † 1	1/1314 (0.08%)
Tremor † 1	1/1314 (0.08%)
Trigeminal neuralgia † 1	3/1314 (0.23%)
Uhthoff's phenomenon † 1	6/1314 (0.46%)
Pregnancy, puerperium and perinatal conditions
Abortion † 1	1/1314 (0.08%)
Abortion missed † 1	3/1314 (0.23%)
Foetal cardiac disorder † 1	1/1314 (0.08%)
Foetal death † 1	1/1314 (0.08%)
Foetal-maternal haemorrhage † 1	1/1314 (0.08%)
HELLP syndrome † 1	1/1314 (0.08%)
Low birth weight baby † 1	1/1314 (0.08%)
Peripartum cardiomyopathy † 1	1/1314 (0.08%)
Placental insufficiency † 1	1/1314 (0.08%)
Pre-eclampsia † 1	1/1314 (0.08%)
Premature separation of placenta † 1	2/1314 (0.15%)
Psychiatric disorders
Adjustment disorder † 1	1/1314 (0.08%)
Affective disorder † 1	1/1314 (0.08%)
Bipolar II disorder † 1	1/1314 (0.08%)
Completed suicide † 1	2/1314 (0.15%)
Depression † 1	2/1314 (0.15%)
Hypomania † 1	1/1314 (0.08%)
Insomnia † 1	1/1314 (0.08%)
Major depression † 1	1/1314 (0.08%)
Mental status changes † 1	4/1314 (0.30%)
Post-traumatic amnestic disorder † 1	1/1314 (0.08%)
Psychogenic pain disorder † 1	1/1314 (0.08%)
Psychogenic tremor † 1	1/1314 (0.08%)
Psychotic disorder † 1	1/1314 (0.08%)
Schizoaffective disorder bipolar type † 1	1/1314 (0.08%)
Self injurious behaviour † 1	1/1314 (0.08%)
Suicidal ideation † 1	6/1314 (0.46%)
Suicide attempt † 1	1/1314 (0.08%)
Renal and urinary disorders
Acute kidney injury † 1	2/1314 (0.15%)
Automatic bladder † 1	1/1314 (0.08%)
Calculus bladder † 1	1/1314 (0.08%)
Calculus ureteric † 1	1/1314 (0.08%)
Glomerulonephritis † 1	1/1314 (0.08%)
Glomerulonephritis membranous † 1	1/1314 (0.08%)
Haematuria † 1	1/1314 (0.08%)
Nephrolithiasis † 1	4/1314 (0.30%)
Renal colic † 1	1/1314 (0.08%)
Renal failure † 1	1/1314 (0.08%)
Renal mass † 1	1/1314 (0.08%)
Renal tubular necrosis † 1	1/1314 (0.08%)
Urinary retention † 1	4/1314 (0.30%)
Reproductive system and breast disorders
Adnexa uteri mass † 1	1/1314 (0.08%)
Cervical dysplasia † 1	4/1314 (0.30%)
Cystocele † 1	2/1314 (0.15%)
Endometrial hyperplasia † 1	1/1314 (0.08%)
Endometriosis † 1	2/1314 (0.15%)
Menometrorrhagia † 1	1/1314 (0.08%)
Menorrhagia † 1	2/1314 (0.15%)
Ovarian cyst † 1	6/1314 (0.46%)
Ovarian haemorrhage † 1	1/1314 (0.08%)
Parovarian cyst † 1	1/1314 (0.08%)
Pelvic adhesions † 1	1/1314 (0.08%)
Rectocele † 1	2/1314 (0.15%)
Vaginal haemorrhage † 1	2/1314 (0.15%)
Vulvar dysplasia † 1	1/1314 (0.08%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/1314 (0.08%)
Apnoea neonatal † 1	1/1314 (0.08%)
Asthma † 1	2/1314 (0.15%)
Bronchospasm † 1	1/1314 (0.08%)
Chronic obstructive pulmonary disease † 1	1/1314 (0.08%)
Dyspnoea † 1	3/1314 (0.23%)
Eosinophilic pneumonia † 1	1/1314 (0.08%)
Hiccups † 1	1/1314 (0.08%)
Interstitial lung disease † 1	1/1314 (0.08%)
Pleural effusion † 1	1/1314 (0.08%)
Pleurisy † 1	2/1314 (0.15%)
Pneumonia aspiration † 1	2/1314 (0.15%)
Pneumonitis † 1	1/1314 (0.08%)
Pneumothorax spontaneous † 1	1/1314 (0.08%)
Pulmonary embolism † 1	2/1314 (0.15%)
Respiratory failure † 1	1/1314 (0.08%)
Sleep apnoea syndrome † 1	1/1314 (0.08%)
Skin and subcutaneous tissue disorders
Erythema nodosum † 1	1/1314 (0.08%)
Hyperhidrosis † 1	1/1314 (0.08%)
Polymorphic eruption of pregnancy † 1	1/1314 (0.08%)
Rash † 1	1/1314 (0.08%)
Rash generalised † 1	2/1314 (0.15%)
Skin ulcer † 1	1/1314 (0.08%)
Urticaria † 1	2/1314 (0.15%)
Surgical and medical procedures
Thyroidectomy † 1	1/1314 (0.08%)
Vascular disorders
Deep vein thrombosis † 1	4/1314 (0.30%)
Haematoma † 1	1/1314 (0.08%)
Hypertension † 1	3/1314 (0.23%)
Hypertensive crisis † 1	1/1314 (0.08%)
Hypotension † 1	1/1314 (0.08%)
Orthostatic hypotension † 1	1/1314 (0.08%)
Pallor † 1	1/1314 (0.08%)
Peripheral arterial occlusive disease † 1	1/1314 (0.08%)
Thrombophlebitis † 1	1/1314 (0.08%)
Vasculitis † 1	1/1314 (0.08%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Alemtuzumab
	Affected / at Risk (%)
Total	1225/1314 (93.23%)
Cardiac disorders
Tachycardia † 1	86/1314 (6.54%)
Endocrine disorders
Autoimmune thyroiditis † 1	67/1314 (5.10%)
Basedow's disease † 1	165/1314 (12.56%)
Hyperthyroidism † 1	142/1314 (10.81%)
Hypothyroidism † 1	140/1314 (10.65%)
Eye disorders
Vision blurred † 1	75/1314 (5.71%)
Gastrointestinal disorders
Abdominal pain † 1	72/1314 (5.48%)
Constipation † 1	104/1314 (7.91%)
Diarrhoea † 1	170/1314 (12.94%)
Dyspepsia † 1	71/1314 (5.40%)
Nausea † 1	206/1314 (15.68%)
Vomiting † 1	130/1314 (9.89%)
General disorders
Fatigue † 1	280/1314 (21.31%)
Pain † 1	85/1314 (6.47%)
Pyrexia † 1	228/1314 (17.35%)
Infections and infestations
Bronchitis † 1	133/1314 (10.12%)
Gastroenteritis † 1	81/1314 (6.16%)
Gastroenteritis viral † 1	85/1314 (6.47%)
Herpes zoster † 1	123/1314 (9.36%)
Influenza † 1	155/1314 (11.80%)
Nasopharyngitis † 1	382/1314 (29.07%)
Oral herpes † 1	78/1314 (5.94%)
Pharyngitis † 1	68/1314 (5.18%)
Sinusitis † 1	186/1314 (14.16%)
Upper respiratory tract infection † 1	272/1314 (20.70%)
Urinary tract infection † 1	360/1314 (27.40%)
Injury, poisoning and procedural complications
Contusion † 1	141/1314 (10.73%)
Fall † 1	87/1314 (6.62%)
Investigations
Blood creatinine increased † 1	68/1314 (5.18%)
Protein urine present † 1	78/1314 (5.94%)
Metabolism and nutrition disorders
Vitamin D deficiency † 1	83/1314 (6.32%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	216/1314 (16.44%)
Back pain † 1	205/1314 (15.60%)
Muscle spasms † 1	132/1314 (10.05%)
Muscular weakness † 1	113/1314 (8.60%)
Musculoskeletal pain † 1	75/1314 (5.71%)
Myalgia † 1	80/1314 (6.09%)
Pain in extremity † 1	189/1314 (14.38%)
Nervous system disorders
Dizziness † 1	130/1314 (9.89%)
Headache † 1	437/1314 (33.26%)
Hypoaesthesia † 1	176/1314 (13.39%)
Multiple sclerosis † 1	70/1314 (5.33%)
Multiple sclerosis relapse † 1	508/1314 (38.66%)
Paraesthesia † 1	168/1314 (12.79%)
Psychiatric disorders
Anxiety † 1	133/1314 (10.12%)
Depression † 1	154/1314 (11.72%)
Insomnia † 1	231/1314 (17.58%)
Renal and urinary disorders
Haematuria † 1	92/1314 (7.00%)
Proteinuria † 1	122/1314 (9.28%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	127/1314 (9.67%)
Oropharyngeal pain † 1	91/1314 (6.93%)
Skin and subcutaneous tissue disorders
Rash † 1	208/1314 (15.83%)
Rash generalised † 1	110/1314 (8.37%)
Urticaria † 1	96/1314 (7.31%)
Vascular disorders
Flushing † 1	79/1314 (6.01%)
Hypertension † 1	92/1314 (7.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

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.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@sanofi.com

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Coles AJ, Jones JL, Vermersch P, Traboulsee A, Bass AD, Boster A, Chan A, Comi G, Fernández Ó, Giovannoni G, Kubala Havrdova E, LaGanke C, Montalban X, Oreja-Guevara C, Piehl F, Wiendl H, Ziemssen T. Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data. Mult Scler. 2022 Apr;28(5):842-846. doi: 10.1177/13524585211061335. Epub 2021 Dec 9. Review.

Kuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, Rӧsch N, Kaiser C, Mitchell CP, Leppert D, Havari E, Kappos L. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS. Mult Scler. 2022 Apr;28(4):573-582. doi: 10.1177/13524585211032348. Epub 2021 Aug 11.

Coles AJ, Arnold DL, Bass AD, Boster AL, Compston DAS, Fernández Ó, Havrdová EK, Nakamura K, Traboulsee A, Ziemssen T, Jacobs A, Margolin DH, Huang X, Daizadeh N, Chirieac MC, Selmaj KW. Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial. Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134. doi: 10.1177/1756286420982134. eCollection 2021.

Bass AD, Arroyo R, Boster AL, Boyko AN, Eichau S, Ionete C, Limmroth V, Navas C, Pelletier D, Pozzilli C, Ravenscroft J, Sousa L, Tintoré M, Uitdehaag BMJ, Baker DP, Daizadeh N, Choudhry Z, Rog D; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years. Mult Scler Relat Disord. 2021 Apr;49:102717. doi: 10.1016/j.msard.2020.102717. Epub 2020 Dec 24.

Horáková D, Boster A, Bertolotto A, Freedman MS, Firmino I, Cavalier SJ, Jacobs AK, Thangavelu K, Daizadeh N, Poole EM, Baker DP, Margolin DH, Ziemssen T; CARE-MS I, CARE-MS II, and CAMMS03409 Investigators. Proportion of alemtuzumab-treated patients converting from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis over 6 years. Mult Scler J Exp Transl Clin. 2020 Dec 18;6(4):2055217320972137. doi: 10.1177/2055217320972137. eCollection 2020 Oct-Dec.

Ziemssen T, Bass AD, Berkovich R, Comi G, Eichau S, Hobart J, Hunter SF, LaGanke C, Limmroth V, Pelletier D, Pozzilli C, Schippling S, Sousa L, Traboulsee A, Uitdehaag BMJ, Van Wijmeersch B, Choudhry Z, Daizadeh N, Singer BA; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study. CNS Drugs. 2020 Sep;34(9):973-988. doi: 10.1007/s40263-020-00749-x.

Gilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2020 Jun 15;17(1):189. doi: 10.1186/s12974-020-01847-9.

Comi G, Alroughani R, Boster AL, Bass AD, Berkovich R, Fernández Ó, Kim HJ, Limmroth V, Lycke J, Macdonell RA, Sharrack B, Singer BA, Vermersch P, Wiendl H, Ziemssen T, Jacobs A, Daizadeh N, Rodriguez CE, Traboulsee A; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies. Mult Scler. 2020 Dec;26(14):1866-1876. doi: 10.1177/1352458519888610. Epub 2019 Nov 25.

Van Wijmeersch B, Singer BA, Boster A, Broadley S, Fernández Ó, Freedman MS, Izquierdo G, Lycke J, Pozzilli C, Sharrack B, Steingo B, Wiendl H, Wray S, Ziemssen T, Chung L, Margolin DH, Thangavelu K, Vermersch P. Efficacy of alemtuzumab over 6 years in relapsing-remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies. Mult Scler. 2020 Nov;26(13):1719-1728. doi: 10.1177/1352458519881759. Epub 2019 Nov 1.

Okai AF, Amezcua L, Berkovich RR, Chinea AR, Edwards KR, Steingo B, Walker A, Jacobs AK, Daizadeh N, Williams MJ; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study). Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25.

Arroyo R, Bury DP, Guo JD, Margolin DH, Melanson M, Daizadeh N, Cella D. Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis. Mult Scler. 2020 Jul;26(8):955-963. doi: 10.1177/1352458519849796. Epub 2019 May 30.

Havrdova E, Arnold DL, Cohen JA, Hartung HP, Fox EJ, Giovannoni G, Schippling S, Selmaj KW, Traboulsee A, Compston DAS, Margolin DH, Thangavelu K, Rodriguez CE, Jody D, Hogan RJ, Xenopoulos P, Panzara MA, Coles AJ; CARE-MS I and CAMMS03409 Investigators. Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology. 2017 Sep 12;89(11):1107-1116. doi: 10.1212/WNL.0000000000004313. Epub 2017 Aug 23. Erratum in: Neurology. 2018 Apr 17;90(16):755.

• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT00930553
• Other Study ID Numbers: CAMMS03409; 2009-010788-18 ( EudraCT Number ); LTE12824 ( Other Identifier: Sanofi )
• First Submitted: June 26, 2009
• First Posted: June 30, 2009
• Results First Submitted: February 16, 2017
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017