TOPAZ: Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02255656
• Collaborator: (none)
• Enrollment: 1,062
• Locations: 131
• Arm: 1
• Actual Duration (Months): 66.2
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate long-term safety of alemtuzumab.

Secondary Objectives:

• To evaluate long term efficacy of alemtuzumab.

• To evaluate the safety profile of participants who received other Disease Modifying Treatment (DMT) following alemtuzumab treatment.

• To evaluate participant-reported Quality of Life (QoL) outcomes and health resource utilization of participant who received alemtuzumab.

• To evaluate as needed re-treatment with alemtuzumab and other DMTs.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Remitting Multiple Sclerosis	Drug: alemtuzumab GZ402673	Phase 4

Detailed Description

The total duration per participants was up to 5.6 years.

As per Study Investigator discretion, participants can be treated with additional courses of alemtuzumab or any commercialized DMTs.

All participants who completed CAMMS03409 were allowed into the study, which might include specific vulnerable populations. If the investigator decided to treat a participant with a course of alemtuzumab, appropriate cautionary measures were applied as indicated in the approved labelling, or, in ex-European Union countries where Lemtrada was not approved, according to the investigator's brochure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1062 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-term Follow-up Study for Multiple Sclerosis Patients Who Have Completed the Alemtuzumab Extension Study (CAMMS03409)
• Actual Study Start Date: Jan 7, 2015
• Actual Primary Completion Date: Jul 15, 2020
• Actual Study Completion Date: Jul 15, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Alemtuzumab All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 milligram per day (mg/day) for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).

Drug: alemtuzumab GZ402673; Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs) [From Baseline until the end of the study (up to a maximum duration of 5.6 years)]

   An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed/worsened during the 'treatment period (time from Baseline until the end of the study LPS13649 [i.e. up to a maximum of 5.6 years]). Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.

2. Number of Participants With Infusion-Associated Reactions (IAR) [Within 24 hours of any alemtuzumab infusion]

   Infusion-associated reactions (IAR) was defined as any adverse event occurring during and within 24 hours of alemtuzumab infusion.

3. Number of Participants With Adverse Events of Special Interest (AESI) [From Baseline until the end of the study (up to a maximum duration of 5.6 years)]

   Adverse events of special interest included the following: hypersensitivity or anaphylaxis; pregnancy of a woman entered in the study; symptomatic overdose (serious or non-serious) with investigational medicinal Product (IMP); increase in alanine transaminase (ALT); autoimmune mediated conditions; hemophagocytic lymphohistiocytosis; progressive multifocal leukoencephalopathy; temporally associated AEs; serious infections; malignancy; and pneumonitis.

4. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities [From Baseline until the end of the study (up to a maximum duration of 5.6 years)]

   Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): less than or equal to (<=)115 grams per liter (g/L)(Male [M]), <= 95 g/L (Female[ F]); greater than or equal to (>=)185 g/L (M), >= 165 g/L (F); Decrease From Baseline (DFB) >= 20 g/L. Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). Red Blood Cells (RBCs): >=6 *10^12/L. Platelets: <100 *10^9/L; >=700 *10^9/L. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Secondary Outcome Measures

1. Annualized Relapse Rate [Up to a maximum duration of 5.6 years]

   Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Annualized relapse rate was obtained from the total number of confirmed relapses that occurred during the treatment follow up time of all participants divided by the total years of follow-up for all participants. The annualized relapse rate was estimated using a negative binomial model with robust variance estimation.

2. Proportion of Participants Who Were Relapse Free [Up to a maximum duration of 5.6 years]

   Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. The proportion of participants who were relapse free (without event) were estimated using the Kaplan-Meier method.

3. Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 [Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60]

   EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes.

4. Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan [Up to a maximum duration of 5.6 years]

   Number of Gd-enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with generalized estimating equation (GEE) adjusted for analysis groups and geographic region as covariates.

5. Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan [Up to a maximum duration of 5.6 years]

   Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.

6. Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan [Up to a maximum duration of 5.6 years]

   Number of new T1 lesions per scan was defined as the total number of new T1 lesion (and New Hypointense T1) that occurred during treatment period divided by the total number of scans performed during treatment period.The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.

7. Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

   The total lesion volume (T1 lesions) was measured by MRI scan.

8. Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

   The total lesion volume (T2 lesions) was measured by MRI scan.

9. Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

   The brain parenchymal fraction was measured by MRI scan.

10. Change From Baseline in Self-reported Quality of Life (QoL) as Assessed by the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Month 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    The MOS SF-36 is an extensively validated and widely used measure of QoL that assesses participants' perceptions of health status and its impact on their lives. It consisted of 36 items organized into 8 scales (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health). Two summary measures of physical and mental health, the PCS and MCS, respectively, were derived from scale aggregates, and were reported in this outcome measure. The score range for each of these 2 summary scores was from 0 (worst) to 100 (best), higher scores indicated better QoL.

11. Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    The FAMS is a self-reported multidimensional index comprising a total 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). Each item (except those for "additional concerns") was rated on a 5-point scale of 0 (lower quality of life) to 4 (higher quality of life). Total FAMS score was the sum of 44 scored items, which ranged from 0 (poor) to 176 (best), with higher numbers reflecting a higher quality of life.

12. Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    The EQ-5D is a generic, standardized instrument that provides a simple, descriptive profile and a single index value for health status used in the clinical and economic evaluation of health care as well as in population health surveys. The EQ-5D comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: some, moderate, and extreme problems. The 5 dimensional 3-level systems was converted into single index utility score ranges from 0 to 100, where 100=best health state; and 0=worst health state; higher scores indicated better outcome.

13. Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48, and 60 [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0 to 100), where 0=worst imaginable health state to 100=best imaginable health state, and higher score indicated better outcome.

14. Modified Healthcare Resource Utilization Questionnaire (HRUQ): Number of Participants Who Reported Change in Employment Situation, Availing of Sick Leaves, Admissions and Stays in Hospital, Rehabilitation Centers or Nursing Homes Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS. Questionnaire addresses the following content areas: employment situation and changes in employment situation due to MS;sick leaves,admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments (eg, stair and bed lift, ramps,rails) and devices (eg,walking aids,wheelchairs); assistance by community or social services (e.g. home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported "Yes" as an answer to "employment situation change; had sick leaves; had hospital admission; had spent time in rehabilitation center and had spent time in a nursing home or a similar institution" questions were reported in this outcome measure.

15. Modified HRUQ: Number of Participants Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS.Questionnaire addresses following content areas: employment situation and changes in employment situation due to MS; admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments(e.g.stair and bed lift,ramps,rails) and devices(e.g.walking aids,wheelchairs);assistance by community or social services(e.g.home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported other changes/changes in lifestyle due to MS, i.e."Yes" as an answer to "had made changes to your house, apartment, car or did you require any special equipment or aids; assistance required; other assistance required" questions were reported in this outcome measure.

16. Health Related Productivity Questionnaire (HRPQ): Number of Participants Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Current employment status of participants (i.e. Part Time/Full Time/Not Employed) was reported in this outcome measure.

17. HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Data for "total scheduled working hours of participants; number of hours missed from work by participants due to MS" were reported in this outcome measure.

18. HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output due to MS were reported in this outcome measure.

19. HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Data for "total scheduled household chores hours; number of hours missed from planned household chores by participants due to MS" were reported in this outcome measure.

20. HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis [Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output for household chores due to MS were reported in this outcome measure.

21. HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis [Baseline up to end of the study (up to a maximum duration of 5.6 years)]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Mean and standard deviation data for duration of MS disease (in months) since the start of MS development in participants was reported in this outcome measure.

22. HRPQ: Number of Participants Who Reported Impact on Work Due to Multiple Sclerosis [Baseline up to end of the study (up to a maximum duration of 5.6 years)]

    Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Number of participants who reported "Yes" as an answer to questions related to impact on work: "forced me to work part-time when I wanted to work full-time; kept me from having a job when I wanted to work full-time; kept me from having a job when I wanted to work part-time; none of the above" questions were reported in this outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

Participant had completed at least 48 months of the Extension Study CAMMS03409. Signed written informed consent form.

Exclusion criteria:

Participant participating in another investigational interventional study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 1086	Cullman	Alabama	United States	00000
2	Investigational Site Number 1031	Phoenix	Arizona	United States	85013
3	Investigational Site Number 1171	Phoenix	Arizona	United States	85018
4	Investigational Site Number 1090	Tucson	Arizona	United States	85704
5	Investigational Site Number 1040	Berkeley	California	United States	94705
6	Investigational Site Number 1152	Fullerton	California	United States	92835
7	Investigational Site Number 1093	Pasadena	California	United States	91105
8	Investigational Site Number 1027	Fort Collins	Colorado	United States	80528
9	Investigational Site Number 1078	Jacksonville	Florida	United States	32209
10	Investigational Site Number 1059	Maitland	Florida	United States	32751
11	Investigational Site Number 1173	Sarasota	Florida	United States	34239
12	Investigational Site Number 1034	Sunrise	Florida	United States	33351
13	Investigational Site Number 1005	Tampa	Florida	United States	33609
14	Investigational Site Number 1049	Tampa	Florida	United States	33612
15	Investigational Site Number 1008	Northbrook	Illinois	United States	60062
16	Investigational Site Number 1001	Fort Wayne	Indiana	United States	46845
17	Investigational Site Number 1024	Indianapolis	Indiana	United States	46202
18	Investigational Site Number 1017	Des Moines	Iowa	United States	50314
19	Investigational Site Number 1022	Kansas City	Kansas	United States	66160
20	Investigational Site Number 1083	Lenexa	Kansas	United States	66214
21	Investigational Site Number 1039	Lexington	Kentucky	United States	40513
22	Investigational Site Number 1021	Louisville	Kentucky	United States	40202
23	Investigational Site Number 1061	Wellesley	Massachusetts	United States	02481
24	Investigational Site Number 1028	Worcester	Massachusetts	United States	01655
25	Investigational Site Number 1025	Ann Arbor	Michigan	United States	48105-2945
26	Investigational Site Number 1020	Detroit	Michigan	United States	48201
27	Investigational Site Number 1054	Traverse City	Michigan	United States	49684
28	Investigational Site Number 1084	Kansas City	Missouri	United States	64111
29	Investigational Site Number 1092	Saint Louis	Missouri	United States	63131
30	Investigational Site Number 1073	Teaneck	New Jersey	United States	07666
31	Investigational Site Number 1014	Albuquerque	New Mexico	United States	87131
32	Investigational Site Number 1081	Mineola	New York	United States	11501
33	Investigational Site Number 1026	New York	New York	United States	10029
34	Investigational Site Number 1160	Patchogue	New York	United States	11772
35	Investigational Site Number 1015	Rochester	New York	United States	14642
36	Investigational Site Number 1053	Syracuse	New York	United States	13202
37	Investigational Site Number 1095	Chapel Hill	North Carolina	United States	27599
38	Investigational Site Number 1082	Winston-Salem	North Carolina	United States	27103
39	Investigational Site Number 1035	Cleveland	Ohio	United States	44195
40	Investigational Site Number 1058	Uniontown	Ohio	United States	44685
41	Investigational Site Number 1067	Oklahoma City	Oklahoma	United States	73104
42	Investigational Site Number 1097	Allentown	Pennsylvania	United States	18103
43	Investigational Site Number 1057	Providence	Rhode Island	United States	02905
44	Investigational Site Number 1163	Cordova	Tennessee	United States	38018
45	Investigational Site Number 1055	Franklin	Tennessee	United States	37064
46	Investigational Site Number 1009	Knoxville	Tennessee	United States	37922
47	Investigational Site Number 1042	Nashville	Tennessee	United States	37215
48	Investigational Site Number 1018	Houston	Texas	United States	77030
49	Investigational Site Number 1002	Round Rock	Texas	United States	78681
50	Investigational Site Number 1046	San Antonio	Texas	United States
51	Investigational Site Number 1037	Vienna	Virginia	United States	22182
52	Investigational Site Number 1068	Seattle	Washington	United States	98122
53	Investigational Site Number 03208	Caba		Argentina	C1061ABD
54	Investigational Site Number 2013	Auchenflower		Australia	4066
55	Investigational Site Number 2001	Heidelberg		Australia	3084
56	Investigational Site Number 2011	Hobart		Australia	7000
57	Investigational Site Number 2012	Kogarah		Australia	2217
58	Investigational Site Number 2003	Melbourne		Australia	3065
59	Investigational Site Number 2002	Parkville		Australia	3050
60	Investigational Site Number 2005	Southport		Australia	4215
61	Investigational Site Number 2009	Sydney		Australia
62	Investigational Site Number 2006	Westmead		Australia	2145
63	Investigational Site Number 5005	Bruxelles		Belgium	1200
64	Investigational Site Number 5004	Esneux		Belgium	4130
65	Investigational Site Number 5001	Leuven		Belgium	3000
66	Investigational Site Number 3006	Porto Alegre		Brazil	90110000
67	Investigational Site Number 3002	Recife		Brazil	52010-040
68	Investigational Site Number 3001	São Paulo		Brazil	01221-000
69	Investigational Site Number 3003	São Paulo		Brazil	05403-000
70	Investigational Site Number 1102	Calgary		Canada	T2N 2T9
71	Investigational Site Number 1105	Gatineau		Canada	J8Y1W2
72	Investigational Site Number 1104	Greenfield Park		Canada	J4V2J2
73	Investigational Site Number 1109	Kingston		Canada	K7L2V7
74	Investigational Site Number 1110	London		Canada	N6A5A5
75	Investigational Site Number 1101	Ottawa		Canada	K1H8L6
76	Investigational Site Number 1106	Vancouver		Canada	V6T1Z3
77	Investigational Site Number 4803	Brno		Czechia	65691
78	Investigational Site Number 4804	Hradec Kralove		Czechia	50005
79	Investigational Site Number 4801	Praha 2		Czechia	12808
80	Investigational Site Number 4802	Teplice		Czechia	41501
81	Investigational Site Number 5302	Aarhus N		Denmark	8200
82	Investigational Site Number 5301	København Ø.		Denmark	2100
83	Investigational Site Number 4602	Berlin		Germany	13347
84	Investigational Site Number 4607	Dresden		Germany	01307
85	Investigational Site Number 4634	Frankfurt am Main		Germany	60590
86	Investigational Site Number 4622	Hamburg		Germany	22307
87	Investigational Site Number 4605	Hannover		Germany	30625
88	Investigational Site Number 4609	Hennigsdorf		Germany	16761
89	Investigational Site Number 4608	München		Germany	81675
90	Investigational Site Number 4610	Rostock		Germany	18147
91	Investigational Site Number 4613	Wermsdorf		Germany	04779
92	Investigational Site Number 5501	Ramat Gan		Israel	52621
93	Investigational Site Number 5505	Tel Aviv		Israel
94	Investigational Site Number 4112	Cagliari		Italy	09126
95	Investigational Site Number 4102	Gallarate (VA)		Italy	21013
96	Investigational Site Number 4106	Orbassano (TO)		Italy	10043
97	Investigational Site Number 4110	Roma		Italy	00189
98	Investigational Site Number 3105	Chihuahua		Mexico	31203
99	Investigational Site Number 3102	Mexico		Mexico	14260
100	Investigational Site Number 4202	Sittard-Geleen		Netherlands	6162BG
101	Investigational Site Number 4902	Krakow		Poland	31-505
102	Investigational Site Number 4901	Lodz		Poland	90-324
103	Investigational Site Number 4903	Lublin		Poland	20-090
104	Investigational Site Number 4904	Poznan		Poland	60-355
105	Investigational Site Number 4905	Warszawa		Poland	02-957
106	Investigational Site Number 6009	Kazan		Russian Federation	420097
107	Investigational Site Number 6001	Moscow		Russian Federation	1217015
108	Investigational Site Number 6005	Moscow		Russian Federation	1217015
109	Investigational Site Number 6003	Moscow		Russian Federation
110	Investigational Site Number 6006	Nizhny Novgorod		Russian Federation
111	Investigational Site Number 6010	Pyatigorsk		Russian Federation
112	Investigational Site Number 6002	Saint-Petersburg		Russian Federation
113	Investigational Site Number 6004	Saint-Petersburg		Russian Federation
114	Investigational Site Number 6008	Saint-Petersburg		Russian Federation
115	Investigational Site Number 6013	Samara		Russian Federation
116	Investigational Site Number 6016	Ufa		Russian Federation
117	Investigational Site Number 4301	Barcelona		Spain	08035
118	Investigational Site Number 4303	Madrid		Spain	28040
119	Investigational Site Number 4305	Málaga		Spain	29010
120	Investigational Site Number 4304	Sevilla		Spain	41071
121	Investigational Site Number 4701	Göteborg		Sweden	41345
122	Investigational Site Number 4702	Umeå		Sweden	90185
123	Investigational Site Number 6102	Kharkov		Ukraine
124	Investigational Site Number 6104	Kiev		Ukraine
125	Investigational Site Number 6103	Lviv		Ukraine
126	Investigational Site Number 4004	Bristol		United Kingdom	BS105NB
127	Investigational Site Number 4001	Cambridge		United Kingdom	CB50QQ
128	Investigational Site Number 4005	Cardiff		United Kingdom	CF44XN
129	Investigational Site Number 4006	London		United Kingdom	E12AT
130	Investigational Site Number 4008	Salford		United Kingdom	M68HD
131	Investigational Site Number 4007	Sheffield		United Kingdom	S102JF

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Jan 28, 2020
• Statistical Analysis Plan - Mar 9, 2020

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02255656
• Other Study ID Numbers: LPS13649; 2013-003884-71; U1111-1148-2987
• First Posted: Oct 2, 2014
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Alemtuzumab

Study Results

Participant Flow

Recruitment Details

The study was conducted at 142 study centers in 21 countries. A total of 1062 participants were screened between 7 January 2015 and 28 June 2016 and were enrolled in this current study (LPS13649 [TOPAZ]).

Pre-assignment Detail

Subgroup analysis ([Delayed Alemtuzumab Treatment[DAT] & Immediate Alemtuzumab Treatment[IAT]subgroup) was performed only for outcome measures and safety analysis. Participants who rolled over from CAMMS223(NCT00050778) to CAMMS03409 (NCT00930553),then subsequently enrolled and took 24 mg alemtuzumab in CAMMS324 (NCT00548405) study, were not considered as part of DAT or IAT subgroup & included in overall group only. Participant flow and Baseline analysis was performed on overall population only.

Arm/Group Title	Alemtuzumab
Arm/Group Description	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 milligram per day (mg/day) for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Period Title: Overall Study
STARTED	1062
COMPLETED	592
NOT COMPLETED	470

Baseline Characteristics

Arm/Group Title	Alemtuzumab
Arm/Group Description	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Overall Participants	1062
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.2 (8.6)
Sex: Female, Male (Count of Participants)
Female	686 64.6%
Male	376 35.4%
Race/Ethnicity, Customized (Count of Participants)
White	988 93%
Black or African American	34 3.2%
Asian	5 0.5%
American Indian or Alaska native	6 0.6%
Other	29 2.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
Description	An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed/worsened during the 'treatment period (time from Baseline until the end of the study LPS13649 [i.e. up to a maximum of 5.6 years]). Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time Frame	From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety analysis set that included all participants who signed the informed consent form (ICF). As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the subcutaneous interferon beta-1a (SC IFNB1a) treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598	1062
Any TEAE	204 19.2%	500 NaN	879 NaN
Any TESAE	55 5.2%	133 NaN	237 NaN
Any TEAE leading to death	0 0%	10 NaN	11 NaN
Any TEAE leading to permanent treatment discontinuation	0 0%	2 NaN	2 NaN

2. Primary Outcome

Title	Number of Participants With Infusion-Associated Reactions (IAR)
Description	Infusion-associated reactions (IAR) was defined as any adverse event occurring during and within 24 hours of alemtuzumab infusion.
Time Frame	Within 24 hours of any alemtuzumab infusion

Outcome Measure Data

Analysis Population Description

Analysis was performed on re-treated population that included all participants who had signed the ICF and who had received study drug in the current study LPS13649. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	83	164	294
Count of Participants [Participants]	48 4.5%	89 NaN	164 NaN

3. Primary Outcome

Title	Number of Participants With Adverse Events of Special Interest (AESI)
Description	Adverse events of special interest included the following: hypersensitivity or anaphylaxis; pregnancy of a woman entered in the study; symptomatic overdose (serious or non-serious) with investigational medicinal Product (IMP); increase in alanine transaminase (ALT); autoimmune mediated conditions; hemophagocytic lymphohistiocytosis; progressive multifocal leukoencephalopathy; temporally associated AEs; serious infections; malignancy; and pneumonitis.
Time Frame	From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], and CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598	1062
Hypersensitivity or anaphylaxis	12 1.1%	25 NaN	44 NaN
Pregnancy of a woman entered in the study	17 1.6%	42 NaN	70 NaN
Symptomatic overdose (serious or non-serious) with IMP	0 0%	0 NaN	0 NaN
Increase in ALT	0 0%	0 NaN	1 NaN
Autoimmune mediated conditions	27 2.5%	66 NaN	100 NaN
Hemophagocytic lymphohistiocytosis	0 0%	0 NaN	0 NaN
Progressive multifocal leukoencephalopathy	0 0%	0 NaN	0 NaN
Temporally associated AEs	2 0.2%	4 NaN	9 NaN
Serious infections	10 0.9%	35 NaN	60 NaN
Malignancy	6 0.6%	15 NaN	27 NaN
Pneumonitis	0 0%	0 NaN	0 NaN

4. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Description	Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): less than or equal to (<=)115 grams per liter (g/L)(Male [M]), <= 95 g/L (Female[ F]); greater than or equal to (>=)185 g/L (M), >= 165 g/L (F); Decrease From Baseline (DFB) >= 20 g/L. Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). Red Blood Cells (RBCs): >=6 *10^12/L. Platelets: <100 *10^9/L; >=700 *10^9/L. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).
Time Frame	From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who had signed the ICF; and received study drug in the TOPAZ study; or in studies CAMMS223,CAMMS323,CAMMS324 or CAMMS03409, and did not complete 48 months of follow-up at the screening visit in the TOPAZ study. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab (Overall)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	214	316	619
Hb:<=115 g/L, <=95 g/L	11 1%	28 NaN	43 NaN
Hb: >=185 g/L, >=165 g/L	2 0.2%	6 NaN	12 NaN
Hb: DFB >=20 g/L	32 3%	50 NaN	98 NaN
Hematocrit: <= 0.37 v/v; <=0.32 v/v	20 1.9%	42 NaN	70 NaN
Hematocrit: >=0.55 v/v; >=0.5 v/v	6 0.6%	14 NaN	26 NaN
RBCs: >=6 *10^12/L	8 0.8%	7 NaN	21 NaN
Platelets: <100 *10^9/L	5 0.5%	16 NaN	25 NaN
Platelets: >=700 *10^9/L	1 0.1%	0 NaN	1 NaN

5. Secondary Outcome

Title	Annualized Relapse Rate
Description	Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Annualized relapse rate was obtained from the total number of confirmed relapses that occurred during the treatment follow up time of all participants divided by the total years of follow-up for all participants. The annualized relapse rate was estimated using a negative binomial model with robust variance estimation.
Time Frame	Up to a maximum duration of 5.6 years

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population which included all enrolled participants who had received study drug in studies CAMMS223, CAMMS323, CAMMS324 or CAMMS03409. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Number (95% Confidence Interval) [relapses per participant per year]	0.1994	0.1608

6. Secondary Outcome

Title	Proportion of Participants Who Were Relapse Free
Description	Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. The proportion of participants who were relapse free (without event) were estimated using the Kaplan-Meier method.
Time Frame	Up to a maximum duration of 5.6 years

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Number (95% Confidence Interval) [proportion of participants]	29.59 2.8%	36.86 NaN

7. Secondary Outcome

Title	Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Description	EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes.
Time Frame	Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 6	0.21 (0.092)	0.03 (0.065)
Month 12	0.27 (0.093)	0.08 (0.065)
Month 18	0.29 (0.096)	0.10 (0.067)
Month 24	0.28 (0.102)	0.15 (0.070)
Month 30	0.34 (0.102)	0.16 (0.071)
Month 36	0.38 (0.103)	0.18 (0.071)
Month 42	0.37 (0.103)	0.24 (0.071)
Month 48	0.46 (0.104)	0.27 (0.072)
Month 54	0.51 (0.106)	0.30 (0.074)
Month 60	0.43 (0.129)	0.32 (0.088)

8. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan
Description	Number of Gd-enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with generalized estimating equation (GEE) adjusted for analysis groups and geographic region as covariates.
Time Frame	Up to a maximum duration of 5.6 years

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Number (95% Confidence Interval) [lesions per scan]	1.307	1.558

9. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
Description	Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.
Time Frame	Up to a maximum duration of 5.6 years

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Number (95% Confidence Interval) [lesions per scan]	8.033	9.564

10. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan
Description	Number of new T1 lesions per scan was defined as the total number of new T1 lesion (and New Hypointense T1) that occurred during treatment period divided by the total number of scans performed during treatment period.The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.
Time Frame	Up to a maximum duration of 5.6 years

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Number (95% Confidence Interval) [lesions per scan]	1.719	1.908

11. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60
Description	The total lesion volume (T1 lesions) was measured by MRI scan.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was preformed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	141.71 (449.79)	64.73 (241.92)
Month 24	130.73 (398.65)	67.48 (262.64)
Month 36	145.57 (404.35)	104.41 (524.62)
Month 48	163.30 (461.38)	76.90 (312.05)
Month 60	202.47 (499.46)	93.61 (260.51)

12. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48, and 60
Description	The total lesion volume (T2 lesions) was measured by MRI scan.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	21.44 (132.04)	9.09 (62.52)
Month 24	17.53 (76.73)	13.89 (62.45)
Month 36	24.24 (94.85)	22.02 (111.95)
Month 48	21.98 (80.06)	19.46 (70.72)
Month 60	32.03 (136.68)	17.95 (75.47)

13. Secondary Outcome

Title	Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48, and 60
Description	The brain parenchymal fraction was measured by MRI scan.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	-1.65 (1.59)	-1.49 (1.55)
Month 24	-1.77 (1.56)	-1.68 (1.64)
Month 36	-1.92 (1.56)	-1.84 (1.71)
Month 48	-2.02 (1.58)	-2.07 (1.78)
Month 60	-2.11 (1.67)	-2.37 (1.65)

14. Secondary Outcome

Title	Change From Baseline in Self-reported Quality of Life (QoL) as Assessed by the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Month 12, 24, 36, 48, and 60
Description	The MOS SF-36 is an extensively validated and widely used measure of QoL that assesses participants' perceptions of health status and its impact on their lives. It consisted of 36 items organized into 8 scales (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health). Two summary measures of physical and mental health, the PCS and MCS, respectively, were derived from scale aggregates, and were reported in this outcome measure. The score range for each of these 2 summary scores was from 0 (worst) to 100 (best), higher scores indicated better QoL.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
PCS: Month 12	0.54 (9.38)	0.88 (8.72)
PCS: Month 24	0.20 (9.25)	0.59 (9.10)
PCS: Month 36	0.08 (9.88)	1.12 (9.18)
PCS: Month 48	-0.52 (10.15)	0.68 (9.57)
PCS: Month 60	-0.23 (8.85)	1.28 (8.88)
MCS: Month 12	2.21 (12.29)	0.89 (11.24)
MCS: Month 24	1.21 (12.23)	1.11 (11.93)
MCS: Month 36	1.55 (12.23)	0.94 (11.88)
MCS: Month 48	1.14 (12.93)	0.35 (12.38)
MCS: Month 60	0.94 (14.01)	0.45 (11.39)

15. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48, and 60
Description	The FAMS is a self-reported multidimensional index comprising a total 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). Each item (except those for "additional concerns") was rated on a 5-point scale of 0 (lower quality of life) to 4 (higher quality of life). Total FAMS score was the sum of 44 scored items, which ranged from 0 (poor) to 176 (best), with higher numbers reflecting a higher quality of life.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	1.05 (29.68)	2.83 (27.07)
Month 24	-0.45 (30.30)	2.73 (28.62)
Month 36	0.82 (30.52)	2.70 (28.94)
Month 48	-3.73 (31.46)	1.16 (29.38)
Month 60	-0.36 (31.25)	2.74 (26.61)

16. Secondary Outcome

Title	Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48, and 60
Description	The EQ-5D is a generic, standardized instrument that provides a simple, descriptive profile and a single index value for health status used in the clinical and economic evaluation of health care as well as in population health surveys. The EQ-5D comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: some, moderate, and extreme problems. The 5 dimensional 3-level systems was converted into single index utility score ranges from 0 to 100, where 100=best health state; and 0=worst health state; higher scores indicated better outcome.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	-0.01 (0.26)	-0.01 (0.26)
Month 24	-0.02 (0.28)	-0.01 (0.26)
Month 36	-0.04 (0.27)	-0.00 (0.26)
Month 48	-0.03 (0.27)	-0.03 (0.27)
Month 60	-0.03 (0.29)	-0.03 (0.25)

17. Secondary Outcome

Title	Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48, and 60
Description	EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0 to 100), where 0=worst imaginable health state to 100=best imaginable health state, and higher score indicated better outcome.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done only on the 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	241	598
Month 12	-2.09 (25.11)	-1.05 (24.57)
Month 24	-1.57 (26.69)	-0.39 (21.44)
Month 36	0.10 (22.61)	1.42 (20.64)
Month 48	-1.08 (23.66)	-0.85 (23.94)
Month 60	-3.26 (27.04)	-0.77 (26.26)

18. Secondary Outcome

Title	Modified Healthcare Resource Utilization Questionnaire (HRUQ): Number of Participants Who Reported Change in Employment Situation, Availing of Sick Leaves, Admissions and Stays in Hospital, Rehabilitation Centers or Nursing Homes Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS. Questionnaire addresses the following content areas: employment situation and changes in employment situation due to MS;sick leaves,admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments (eg, stair and bed lift, ramps,rails) and devices (eg,walking aids,wheelchairs); assistance by community or social services (e.g. home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported "Yes" as an answer to "employment situation change; had sick leaves; had hospital admission; had spent time in rehabilitation center and had spent time in a nursing home or a similar institution" questions were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	231	573	1020
Employment situation change: Month 0	3 0.3%	7 NaN	12 NaN
Employment situation change: Month 12	11 1%	25 NaN	44 NaN
Employment situation change: Month 24	14 1.3%	19 NaN	40 NaN
Employment situation change: Month 36	12 1.1%	26 NaN	44 NaN
Employment situation change: Month 48	4 0.4%	24 NaN	38 NaN
Employment situation change: Month 60	3 0.3%	8 NaN	14 NaN
Had sick leaves: Month 0	6 0.6%	14 NaN	21 NaN
Had sick leaves: Month 12	19 1.8%	45 NaN	77 NaN
Had sick leaves: Month 24	23 2.2%	42 NaN	80 NaN
Had sick leaves: Month 36	21 2%	44 NaN	78 NaN
Had sick leaves: Month 48	18 1.7%	31 NaN	60 NaN
Had sick leaves: Month 60	9 0.8%	10 NaN	25 NaN
Had hospital admission: Month 0	4 0.4%	23 NaN	32 NaN
Had hospital admission: Month 12	28 2.6%	59 NaN	109 NaN
Had hospital admission: Month 24	26 2.4%	53 NaN	95 NaN
Had hospital admission: Month 36	27 2.5%	58 NaN	106 NaN
Had hospital admission: Month 48	20 1.9%	51 NaN	89 NaN
Had hospital admission: Month 60	12 1.1%	11 NaN	28 NaN
Had spent time in rehabilitation center: Month 0	0 0%	6 NaN	8 NaN
Had spent time in rehabilitation center: Month 12	12 1.1%	21 NaN	45 NaN
Had spent time in rehabilitation center: Month 24	17 1.6%	18 NaN	45 NaN
Had spent time in rehabilitation center: Month 36	12 1.1%	19 NaN	36 NaN
Had spent time in rehabilitation center: Month 48	12 1.1%	24 NaN	45 NaN
Had spent time in rehabilitation center: Month 60	5 0.5%	6 NaN	18 NaN
Had spent time in a nursing home: Month 0	0 0%	0 NaN	0 NaN
Had spent time in a nursing home: Month 12	0 0%	5 NaN	8 NaN
Had spent time in a nursing home: Month 24	3 0.3%	4 NaN	7 NaN
Had spent time in a nursing home: Month 36	3 0.3%	3 NaN	8 NaN
Had spent time in a nursing home: Month 48	4 0.4%	4 NaN	11 NaN
Had spent time in a nursing home: Month 60	0 0%	4 NaN	6 NaN

19. Secondary Outcome

Title	Modified HRUQ: Number of Participants Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS.Questionnaire addresses following content areas: employment situation and changes in employment situation due to MS; admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments(e.g.stair and bed lift,ramps,rails) and devices(e.g.walking aids,wheelchairs);assistance by community or social services(e.g.home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported other changes/changes in lifestyle due to MS, i.e."Yes" as an answer to "had made changes to your house, apartment, car or did you require any special equipment or aids; assistance required; other assistance required" questions were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	231	573	1020
Had made changes to your house, apartment, car: Month 0	0 0%	3 NaN	7 NaN
Had made changes to your house, apartment, car: Month 12	11 1%	21 NaN	42 NaN
Had made changes to your house, apartment, car: Month 24	10 0.9%	25 NaN	47 NaN
Had made changes to your house, apartment, car: Month 36	16 1.5%	15 NaN	45 NaN
Had made changes to your house, apartment, car: Month 48	10 0.9%	25 NaN	42 NaN
Had made changes to your house, apartment, car: Month 60	5 0.5%	3 NaN	12 NaN
Had required assistance: Month 0	4 0.4%	10 NaN	24 NaN
Had required assistance: Month 12	24 2.3%	45 NaN	88 NaN
Had required assistance: Month 24	26 2.4%	44 NaN	86 NaN
Had required assistance: Month 36	22 2.1%	35 NaN	79 NaN
Had required assistance: Month 48	12 1.1%	45 NaN	75 NaN
Had required assistance: Month 60	8 0.8%	10 NaN	26 NaN
Had required other assistance: Month 0	15 1.4%	48 NaN	77 NaN
Had required other assistance: Month 12	57 5.4%	144 NaN	252 NaN
Had required other assistance: Month 24	57 5.4%	135 NaN	241 NaN
Had required other assistance: Month 36	48 4.5%	119 NaN	215 NaN
Had required other assistance: Month 48	49 4.6%	119 NaN	211 NaN
Had required other assistance: Month 60	22 2.1%	27 NaN	66 NaN

20. Secondary Outcome

Title	Health Related Productivity Questionnaire (HRPQ): Number of Participants Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Current employment status of participants (i.e. Part Time/Full Time/Not Employed) was reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	234	575	1025
Full time: Month 0	127 12%	297 NaN	528 NaN
Part time: Month 0	20 1.9%	54 NaN	98 NaN
Not employed: Month 0	87 8.2%	224 NaN	399 NaN
Full time: Month 12	121 11.4%	291 NaN	511 NaN
Part time: Month 12	20 1.9%	53 NaN	104 NaN
Not employed: Month 12	88 8.3%	225 NaN	398 NaN
Full time: Month 24	118 11.1%	273 NaN	488 NaN
Part time: Month 24	21 2%	66 NaN	117 NaN
Not employed: Month 24	84 7.9%	210 NaN	375 NaN
Full time: Month 36	109 10.3%	273 NaN	478 NaN
Part time: Month 36	23 2.2%	57 NaN	108 NaN
Not employed: Month 36	84 7.9%	200 NaN	357 NaN
Full time: Month 48	108 10.2%	225 NaN	424 NaN
Part time: Month 48	21 2%	57 NaN	103 NaN
Not employed: Month 48	75 7.1%	187 NaN	333 NaN
Full time: Month 60	37 3.5%	97 NaN	189 NaN
Part time: Month 60	10 0.9%	18 NaN	43 NaN
Not employed: Month 60	35 3.3%	68 NaN	142 NaN

21. Secondary Outcome

Title	HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Data for "total scheduled working hours of participants; number of hours missed from work by participants due to MS" were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	153	380	675
Total scheduled working hours: Month 0	34.0 (14.6)	32.2 (16.1)	32.9 (16.1)
Total scheduled working hours: Month 12	33.6 (15.4)	32.3 (16.6)	32.5 (16.6)
Total scheduled working hours: Month 24	33.2 (15.5)	30.8 (16.1)	31.6 (16.1)
Total scheduled working hours: Month 36	33.6 (16.4)	33.1 (15.1)	33.3 (15.3)
Total scheduled working hours: Month 48	34.4 (19.7)	31.3 (16.3)	32.9 (17.0)
Total scheduled working hours: Month 60	27.3 (18.9)	31.1 (15.8)	31.1 (16.6)
Number of hours missed from work: Month 0	9.8 (12.1)	15.2 (15.0)	11.7 (12.8)
Number of hours missed from work: Month 12	6.7 (3.6)	10.1 (12.2)	9.0 (10.2)
Number of hours missed from work: Month 24	6.7 (6.1)	10.6 (11.3)	10.4 (10.9)
Number of hours missed from work: Month 36	9.3 (5.9)	24.7 (65.4)	18.7 (50.8)
Number of hours missed from work: Month 48	21.5 (23.1)	37.7 (107.6)	28.0 (77.1)
Number of hours missed from work: Month 60	14.5 (13.4)	13.4 (13.4)	13.9 (13.0)

22. Secondary Outcome

Title	HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output due to MS were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab (Overall)
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	145	351	622
Month 0	6.2 (14.4)	10.2 (22.3)	8.5 (19.5)
Month 12	8.7 (18.0)	9.5 (21.5)	9.0 (20.2)
Month 24	9.9 (20.4)	9.4 (21.2)	9.8 (21.3)
Month 36	9.2 (20.0)	9.9 (21.3)	9.4 (19.9)
Month 48	12.2 (25.4)	9.3 (21.7)	9.7 (22.0)
Month 60	11.7 (22.3)	8.1 (18.9)	9.2 (19.9)

23. Secondary Outcome

Title	HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Data for "total scheduled household chores hours; number of hours missed from planned household chores by participants due to MS" were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population.Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	228	562	1004
Total scheduled household chores hours: Month 0	9.8 (8.3)	11.0 (11.0)	10.8 (10.6)
Total scheduled household chores hours: Month 12	10.3 (10.1)	11.1 (11.7)	10.9 (11.5)
Total scheduled household chores hours: Month 24	10.2 (11.6)	10.9 (11.4)	10.6 (11.4)
Total scheduled household chores hours: Month 36	9.7 (10.2)	11.7 (13.1)	11.0 (12.1)
Total scheduled household chores hours: Month 48	9.9 (8.9)	10.5 (10.6)	10.3 (10.3)
Total scheduled household chores hours: Month 60	10.4 (8.7)	11.2 (11.1)	11.5 (12.6)
Number of hours missed from household chores: Month 0	4.7 (3.3)	6.5 (6.9)	6.0 (5.9)
Number of hours missed from household chores: Month 12	4.9 (3.5)	6.8 (7.7)	6.2 (6.6)
Number of hours missed from household chores: Month 24	7.8 (9.0)	7.1 (10.6)	6.6 (9.3)
Number of hours missed from household chores: Month 36	6.1 (7.4)	7.7 (14.2)	7.0 (11.7)
Number of hours missed from household chores: Month 48	4.8 (4.3)	6.2 (10.6)	5.7 (8.4)
Number of hours missed from household chores: Month 60	5.3 (5.2)	5.8 (5.1)	5.9 (5.1)

24. Secondary Outcome

Title	HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Percentage impact on work output for household chores due to MS were reported in this outcome measure.
Time Frame	Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	212	531	947
Month 0	16.0 (23.8)	16.4 (26.0)	16.8 (25.8)
Month 12	18.3 (27.3)	16.6 (26.6)	17.7 (27.5)
Month 24	20.3 (28.5)	18.5 (27.4)	19.4 (28.1)
Month 36	17.5 (25.9)	16.5 (26.2)	17.6 (26.6)
Month 48	19.8 (28.8)	17.0 (26.8)	18.6 (27.7)
Month 60	18.8 (28.3)	13.1 (22.9)	14.8 (25.0)

25. Secondary Outcome

Title	HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Mean and standard deviation data for duration of MS disease (in months) since the start of MS development in participants was reported in this outcome measure.
Time Frame	Baseline up to end of the study (up to a maximum duration of 5.6 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	228	559	997
Mean (Standard Deviation) [months]	10.3 (4.0)	10.2 (5.0)	10.5 (4.5)

26. Secondary Outcome

Title	HRPQ: Number of Participants Who Reported Impact on Work Due to Multiple Sclerosis
Description	Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Number of participants who reported "Yes" as an answer to questions related to impact on work: "forced me to work part-time when I wanted to work full-time; kept me from having a job when I wanted to work full-time; kept me from having a job when I wanted to work part-time; none of the above" questions were reported in this outcome measure.
Time Frame	Baseline up to end of the study (up to a maximum duration of 5.6 years)

Outcome Measure Data

Analysis Population Description

Analysis was performed on efficacy population. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants with available data for each specified category. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)	Initial Alemtuzumab Treatment (IAT)	Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).	All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
Measure Participants	164	399	709
My MS or treatments forced me to work part-time when I wanted to work full-time	22 2.1%	81 NaN	125 NaN
My MS or treatments kept me from having a job when I wanted to work full-time	32 3%	88 NaN	168 NaN
My MS or treatments kept me from having a job when I wanted to work part-time	20 1.9%	42 NaN	81 NaN
None of the above	164 15.4%	399 NaN	709 NaN

Adverse Events

Time Frame	All Adverse Events were collected from the Baseline until the end of the study (up to a maximum duration of 5.6 years).
Adverse Event Reporting Description	Reported adverse events and death were TEAEs that is AEs that developed/worsened during the 'treatment period' (time from Baseline until the end of the study). Analysis was performed on safety population. As pre-specified, safety analysis was done on the overall population along with 2 subgroups (DAT and IAT).
Arm/Group Title	Delayed Alemtuzumab Treatment (DAT)		Initial Alemtuzumab Treatment (IAT)		Alemtuzumab
Arm/Group Description	Participants from the SC IFNB1a treatment arms of studies CAMMS323 and CAMMS324, who received their initial 2 treatment courses of alemtuzumab during the CAMMS03409 extension study were included in the DAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).		Participants from the 12 mg/day alemtuzumab treatment arms of the studies CAMMS323 and CAMMS324 (who were subsequently enrolled in CAMMS03409 extension study and then entered in this study LPS13649) were included in the IAT subgroup of the current study (LPS13649). Participants received alemtuzumab intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).		All Participants who completed the study CAMMS03409 (extension study of CAMMS223 [NCT00050778], CAMMS323 [NCT00530348], or CAMMS324 [NCT00548405]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 mg/day for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).
All Cause Mortality
	Delayed Alemtuzumab Treatment (DAT)		Initial Alemtuzumab Treatment (IAT)		Alemtuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/241 (0%)		10/598 (1.7%)		11/1062 (1%)
Serious Adverse Events
	Delayed Alemtuzumab Treatment (DAT)		Initial Alemtuzumab Treatment (IAT)		Alemtuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/241 (22.8%)		133/598 (22.2%)		237/1062 (22.3%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Immune Thrombocytopenia	0/241 (0%)	0	2/598 (0.3%)	4	2/1062 (0.2%)	4
Lymphopenia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Thrombocytopenia	1/241 (0.4%)	1	2/598 (0.3%)	2	3/1062 (0.3%)	3
Cardiac disorders
Acute Left Ventricular Failure	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Acute Myocardial Infarction	1/241 (0.4%)	1	2/598 (0.3%)	2	4/1062 (0.4%)	4
Atrioventricular Block	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Bundle Branch Block Left	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Coronary Artery Disease	1/241 (0.4%)	1	0/598 (0%)	0	2/1062 (0.2%)	2
Left Ventricular Dysfunction	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Mitral Valve Incompetence	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Myocardial Infarction	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Pericardial Effusion	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Sinus Tachycardia	1/241 (0.4%)	1	0/598 (0%)	0	2/1062 (0.2%)	2
Ventricular Arrhythmia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Congenital, familial and genetic disorders
Atrial Septal Defect	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Congenital Cystic Kidney Disease	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Congenital Nail Disorder	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Foetal Chromosome Abnormality	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Trisomy 21	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Ear and labyrinth disorders
Haematotympanum	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Vertigo	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Endocrine disorders
Autoimmune Hypothyroidism	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Autoimmune Thyroid Disorder	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Autoimmune Thyroiditis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Basedow's Disease	2/241 (0.8%)	2	4/598 (0.7%)	4	7/1062 (0.7%)	7
Hyperthyroidism	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	3
Hypothyroidism	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Thyroid Dermatopathy	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Eye disorders
Cataract	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Endocrine Ophthalmopathy	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Exophthalmos	1/241 (0.4%)	2	0/598 (0%)	0	1/1062 (0.1%)	2
Eyelid Ptosis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Glaucoma	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Optic Ischaemic Neuropathy	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Periorbital Oedema	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Gastrointestinal disorders
Abdominal Pain Upper	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Colitis Ulcerative	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Diarrhoea	1/241 (0.4%)	2	0/598 (0%)	0	1/1062 (0.1%)	2
Gastric Ulcer Perforation	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Gastritis	0/241 (0%)	0	2/598 (0.3%)	2	3/1062 (0.3%)	3
Haematemesis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Haemorrhoids	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Inguinal Hernia	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Intestinal Ischaemia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Intestinal Obstruction	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Intussusception	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Obstructive Pancreatitis	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Pancreatitis Acute	2/241 (0.8%)	2	0/598 (0%)	0	2/1062 (0.2%)	2
Pancreatitis Chronic	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	2
Small Intestinal Obstruction	0/241 (0%)	0	1/598 (0.2%)	3	1/1062 (0.1%)	3
General disorders
Catheter Site Pain	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Complication Associated With Device	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Death	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Drug Intolerance	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Hyperthermia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Non-Cardiac Chest Pain	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Pyrexia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Sudden Death	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Hepatobiliary disorders
Cholecystitis	2/241 (0.8%)	2	0/598 (0%)	0	3/1062 (0.3%)	3
Cholelithiasis	1/241 (0.4%)	1	2/598 (0.3%)	2	4/1062 (0.4%)	4
Immune system disorders
Drug Hypersensitivity	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Immune Reconstitution Inflammatory Syndrome	1/241 (0.4%)	2	0/598 (0%)	0	1/1062 (0.1%)	2
Sarcoidosis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Infections and infestations
Abdominal Abscess	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Abscess Rupture	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Anal Abscess	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Appendicitis	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Bacteraemia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Bacterial Sepsis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Cellulitis	0/241 (0%)	0	3/598 (0.5%)	7	4/1062 (0.4%)	8
Cellulitis Staphylococcal	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Clostridium Difficile Colitis	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Clostridium Difficile Infection	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Diverticulitis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Endocarditis	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	2
Erysipelas	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Escherichia Urinary Tract Infection	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Gangrene	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Gastroenteritis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Gastrointestinal Bacterial Infection	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Herpes Zoster	0/241 (0%)	0	3/598 (0.5%)	3	3/1062 (0.3%)	3
Herpes Zoster Infection Neurological	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Infected Bite	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Infected Lymphocele	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Influenza	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Klebsiella Infection	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Localised Infection	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Neonatal Pneumonia	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Osteomyelitis Acute	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Periodontitis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Pneumonia	1/241 (0.4%)	1	4/598 (0.7%)	4	9/1062 (0.8%)	10
Pneumonia Bacterial	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Pneumonia Streptococcal	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Postoperative Wound Infection	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Pyelonephritis	1/241 (0.4%)	1	1/598 (0.2%)	1	3/1062 (0.3%)	3
Scrotal Abscess	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Sepsis	1/241 (0.4%)	1	2/598 (0.3%)	3	5/1062 (0.5%)	7
Septic Shock	0/241 (0%)	0	3/598 (0.5%)	3	4/1062 (0.4%)	4
Urinary Tract Infection	2/241 (0.8%)	3	4/598 (0.7%)	4	9/1062 (0.8%)	10
Urinary Tract Infection Bacterial	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Urosepsis	0/241 (0%)	0	1/598 (0.2%)	1	2/1062 (0.2%)	2
Uterine Infection	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Injury, poisoning and procedural complications
Accidental Overdose	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Ankle Fracture	0/241 (0%)	0	2/598 (0.3%)	2	3/1062 (0.3%)	3
Brain Contusion	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Burns Third Degree	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Craniocerebral Injury	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Face Injury	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Fall	1/241 (0.4%)	2	1/598 (0.2%)	1	2/1062 (0.2%)	3
Femur Fracture	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Foot Fracture	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Head Injury	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Humerus Fracture	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Induced Abortion Failed	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Intentional Overdose	0/241 (0%)	0	1/598 (0.2%)	3	1/1062 (0.1%)	3
Meniscus Injury	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Post Procedural Hypotension	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Radius Fracture	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Skull Fractured Base	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Subdural Haematoma	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Tendon Rupture	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Tibia Fracture	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Traumatic Fracture	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Ulna Fracture	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Upper Limb Fracture	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Wrist Fracture	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Investigations
Antiphospholipid Antibodies Positive	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Human Papilloma Virus Test Positive	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Lymphocyte Count Decreased	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Metabolism and nutrition disorders
Dehydration	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Diabetes Mellitus	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Diabetic Ketosis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Electrolyte Imbalance	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Hyperglycaemia	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Type 1 Diabetes Mellitus	0/241 (0%)	0	3/598 (0.5%)	4	3/1062 (0.3%)	4
Type 2 Diabetes Mellitus	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Back Pain	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Joint Contracture	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Muscular Weakness	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Musculoskeletal Pain	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Osteonecrosis	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Systemic Lupus Erythematosus	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	0/241 (0%)	0	1/598 (0.2%)	3	2/1062 (0.2%)	4
Breast Cancer	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Brenner Tumour	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Cervix Carcinoma Stage 0	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Cutaneous T-Cell Lymphoma	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Gallbladder Cancer Stage Iii	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Intraductal Proliferative Breast Lesion	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Invasive Ductal Breast Carcinoma	0/241 (0%)	0	1/598 (0.2%)	1	3/1062 (0.3%)	3
Invasive Lobular Breast Carcinoma	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Laryngeal Squamous Cell Carcinoma	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Lung Squamous Cell Carcinoma Stage Iii	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Malignant Melanoma	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Malignant Melanoma In Situ	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Malignant Neoplasm Of Unknown Primary Site	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Neuroma	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Non-Hodgkin's Lymphoma	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Ovarian Adenoma	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Ovarian Cancer	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Ovarian Germ Cell Teratoma	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Prostate Cancer	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Rectal Cancer Metastatic	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Squamous Cell Carcinoma Of Skin	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Uterine Cancer	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Uterine Leiomyoma	1/241 (0.4%)	1	3/598 (0.5%)	3	5/1062 (0.5%)	5
Nervous system disorders
Ataxia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Dizziness	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Dysarthria	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Encephalopathy	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Epilepsy	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Generalised Tonic-Clonic Seizure	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Headache	2/241 (0.8%)	2	1/598 (0.2%)	1	3/1062 (0.3%)	3
Limbic Encephalitis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Loss Of Consciousness	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Lumbosacral Radiculopathy	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Multiple Sclerosis	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Multiple Sclerosis Relapse	6/241 (2.5%)	6	18/598 (3%)	30	30/1062 (2.8%)	43
Optic Neuritis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Partial Seizures	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Post Herpetic Neuralgia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Postural Tremor	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Resting Tremor	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Sciatica	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Seizure	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Syncope	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Toxic Encephalopathy	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Trigeminal Neuralgia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Uhthoff's Phenomenon	3/241 (1.2%)	3	5/598 (0.8%)	5	9/1062 (0.8%)	9
Pregnancy, puerperium and perinatal conditions
Abortion Missed	0/241 (0%)	0	0/598 (0%)	0	2/1062 (0.2%)	2
Abortion Spontaneous	3/241 (1.2%)	5	6/598 (1%)	7	11/1062 (1%)	15
Anembryonic Gestation	1/241 (0.4%)	2	0/598 (0%)	0	1/1062 (0.1%)	2
Ectopic Pregnancy	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Foetal Distress Syndrome	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Hellp Syndrome	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Missed Labour	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Pre-Eclampsia	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Pregnancy	2/241 (0.8%)	3	4/598 (0.7%)	4	7/1062 (0.7%)	8
Prolonged Labour	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Psychiatric disorders
Alcoholism	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Behaviour Disorder	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Completed Suicide	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Confusional State	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Depression	2/241 (0.8%)	2	2/598 (0.3%)	2	4/1062 (0.4%)	4
Depression Suicidal	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Drug Abuse	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Major Depression	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Mental Disorder	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Substance-Induced Psychotic Disorder	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Suicidal Ideation	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Suicide Attempt	2/241 (0.8%)	2	2/598 (0.3%)	3	4/1062 (0.4%)	5
Renal and urinary disorders
Acute Kidney Injury	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Cystitis Haemorrhagic	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Lupus Nephritis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Nephrolithiasis	2/241 (0.8%)	3	2/598 (0.3%)	2	5/1062 (0.5%)	7
Renal Colic	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Renal Injury	0/241 (0%)	0	1/598 (0.2%)	2	1/1062 (0.1%)	2
Reproductive system and breast disorders
Cervical Dysplasia	1/241 (0.4%)	1	3/598 (0.5%)	3	5/1062 (0.5%)	5
Cystocele	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Endometriosis	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Female Genital Tract Fistula	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Menorrhagia	1/241 (0.4%)	1	0/598 (0%)	0	2/1062 (0.2%)	2
Metrorrhagia	0/241 (0%)	0	1/598 (0.2%)	1	2/1062 (0.2%)	2
Uterine Polyp	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Vaginal Haemorrhage	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/241 (0.4%)	1	1/598 (0.2%)	1	3/1062 (0.3%)	3
Asthma	1/241 (0.4%)	1	1/598 (0.2%)	1	2/1062 (0.2%)	2
Atelectasis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Dyspnoea	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Nasal Septum Deviation	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Organising Pneumonia	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Pneumomediastinum	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Pulmonary Embolism	0/241 (0%)	0	3/598 (0.5%)	3	3/1062 (0.3%)	3
Pulmonary Fibrosis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Skin and subcutaneous tissue disorders
Angioedema	0/241 (0%)	0	2/598 (0.3%)	3	2/1062 (0.2%)	3
Decubitus Ulcer	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Erythema	1/241 (0.4%)	1	0/598 (0%)	0	1/1062 (0.1%)	1
Rash	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Skin Ulcer	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Vascular disorders
Deep Vein Thrombosis	0/241 (0%)	0	1/598 (0.2%)	1	1/1062 (0.1%)	1
Flushing	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Hypertension	0/241 (0%)	0	0/598 (0%)	0	1/1062 (0.1%)	1
Peripheral Artery Thrombosis	0/241 (0%)	0	2/598 (0.3%)	2	2/1062 (0.2%)	2
Other (Not Including Serious) Adverse Events
	Delayed Alemtuzumab Treatment (DAT)		Initial Alemtuzumab Treatment (IAT)		Alemtuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	150/241 (62.2%)		338/598 (56.5%)		601/1062 (56.6%)
Gastrointestinal disorders
Nausea	13/241 (5.4%)	13	18/598 (3%)	18	37/1062 (3.5%)	37
General disorders
Fatigue	15/241 (6.2%)	17	19/598 (3.2%)	19	43/1062 (4%)	45
Infections and infestations
Bronchitis	14/241 (5.8%)	17	44/598 (7.4%)	54	67/1062 (6.3%)	81
Herpes Zoster	15/241 (6.2%)	16	29/598 (4.8%)	35	50/1062 (4.7%)	57
Influenza	13/241 (5.4%)	13	25/598 (4.2%)	28	48/1062 (4.5%)	55
Nasopharyngitis	34/241 (14.1%)	60	73/598 (12.2%)	112	129/1062 (12.1%)	204
Sinusitis	11/241 (4.6%)	11	34/598 (5.7%)	45	57/1062 (5.4%)	71
Upper Respiratory Tract Infection	27/241 (11.2%)	29	50/598 (8.4%)	73	96/1062 (9%)	123
Urinary Tract Infection	37/241 (15.4%)	56	78/598 (13%)	143	151/1062 (14.2%)	271
Injury, poisoning and procedural complications
Fall	15/241 (6.2%)	20	27/598 (4.5%)	34	54/1062 (5.1%)	74
Musculoskeletal and connective tissue disorders
Arthralgia	19/241 (7.9%)	27	39/598 (6.5%)	45	69/1062 (6.5%)	86
Back Pain	16/241 (6.6%)	16	30/598 (5%)	34	62/1062 (5.8%)	68
Nervous system disorders
Headache	37/241 (15.4%)	52	67/598 (11.2%)	87	125/1062 (11.8%)	164
Pregnancy, puerperium and perinatal conditions
Pregnancy	14/241 (5.8%)	23	39/598 (6.5%)	46	63/1062 (5.9%)	86
Psychiatric disorders
Depression	13/241 (5.4%)	13	25/598 (4.2%)	26	43/1062 (4%)	45
Insomnia	16/241 (6.6%)	17	29/598 (4.8%)	32	57/1062 (5.4%)	62
Skin and subcutaneous tissue disorders
Rash	13/241 (5.4%)	16	26/598 (4.3%)	34	51/1062 (4.8%)	64

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.