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

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

Study Description

Brief Summary:

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

1. To examine the long term safety and efficacy of alemtuzumab treatment in participants who received alemtuzumab as their study treatment in one of the prior studies.
2. To examine the safety and efficacy of initial alemtuzumab treatment in this study for participants who received Rebif® (interferon beta-1a) as their study treatment in one of the prior studies.
3. To determine the safety and efficacy of additional "as needed" alemtuzumab treatment courses. This applied both to participants who received alemtuzumab for the first time in one of the prior studies or for the first time in this extension study.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis, Relapsing-Remitting	Biological: alemtuzumab	Phase 3

Detailed Description:

Alemtuzumab treatment was on a fixed schedule of two treatment courses a year apart for participants who received Rebif® in one of the prior Genzyme-sponsored studies of alemtuzumab or on an as needed schedule (e.g. due to documented evidence of resumed Multiple Sclerosis [MS] activity) for participants who had already completed a fixed schedule of treatment with alemtuzumab in one of the prior Genzyme-sponsored studies. There was no comparison treatment in this study. All participants were required to return to their study site every 3 months for neurologic and other assessments. In addition, safety-related laboratory tests and surveys were performed at least monthly. Participation in the extension study was at least 48 months from enrollment. Study duration could be extended to allow participants to remain in the study until a follow-up study was available in their country or through month 60 (month 72 in USA), whichever occurred first.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1314 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
• Study Start Date: August 2009
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: February 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Previously treated with alemtuzumab; Alemtuzumab 12 mg per day administered through IV, once a day for 3 consecutive days (participants might receive additional cycles of alemtuzumab upon documented evidence of resumed disease activity, but not within same 12-month period)	Biological: alemtuzumab; Alemtuzumab 12 mg/day IV infusion on 5 consecutive days if the participants had no prior alemtuzumab exposure (ie, first treatment course). All subsequent treatment courses were for 3 days only.
Experimental: Previously treated with interferon beta-1a (Rebif®); Alemtuzumab 12 mg per day administered through IV, once a day for 5 consecutive days during the first cycle and 12 mg per day administered through IV, once a day for 3 consecutive days during the second cycle, 12 months later. Participants might qualify for as-needed retreatment (12 mg per day administered through IV, once a day for 3 consecutive days) after their second fixed annual cycle.	Biological: alemtuzumab; Alemtuzumab 12 mg/day IV infusion on 5 consecutive days if the participants had no prior alemtuzumab exposure (ie, first treatment course). All subsequent treatment courses were for 3 days only.

Outcome Measures

Primary Outcome Measures :

1. Annualized Relapse Rate (ARR) [ Time Frame: Year 3, 4, 5, 6 from the Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively) ]
   Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.
2. Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
   Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
3. Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment [ Time Frame: Year 1 prior to retreatment, Year 1, 2, 3 after retreatment ]
   Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.
4. Number of Participants With Sustained Accumulation of Disability (SAD) [ Time Frame: Baseline (Year 0) up to Year 6 ]
   SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.
5. Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
   SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Secondary Outcome Measures :

1. Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6 [ Time Frame: Baseline (Year 0) up to Year 6 ]
   SRD was defined as a ≥1 point decrease in EDSS score lasting >= 6 months. SRD is only applicable to participants with a baseline EDSS score of >= 2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.
2. Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study [ Time Frame: Extension study (CAMMS03409) baseline up to Extension Year 2 ]
   SRD was defined as a >=1 point decrease in EDSS score lasting >=6 months. SRD is only applicable to participants with a baseline EDSS score of ≥2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
3. Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 ]
   EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 [NCT00530348] or CAMMS324 [NCT00548405]) value from EDSS scores at specified time points.
4. Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
   EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.
5. Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment [ Time Frame: Retreatment baseline, Year 1, 2 and 3 after retreatment baseline ]
   EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.
6. Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity [ Time Frame: Year 3, 4, 5 and 6 ]
   Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.
7. Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
   Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
8. Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment [ Time Frame: Retreatment Baseline, Year 1, 2 and 3 after retreatment ]
   Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.
9. Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 ]
   Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.
10. Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity [ Time Frame: Year 3, 4, 5 and 6 ]
    Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.
11. Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 ]
    Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.
12. Percentage of Relapse Free Participants [ Time Frame: Year 3, 4, 5 and 6 ]
    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.
13. Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension group", "alemtuzumab Treatment CAMMS324 Extension" group, respectively),Year 3, 4, 5 and 6 ]
    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
14. Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
15. Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 ]
    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.
16. Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.
17. Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6 ]
    FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.
18. Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
    FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.
19. Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6 [ Time Frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5 and 6 ]
    EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.
20. Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison [ Time Frame: Baseline (Year 0 of initial studies) up to Year 4 ]
    EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received disease modifying treatments (other than glatiramer acetate or interferon beta); or
• 2.Received Rebif® in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received alternative disease modifying treatments (other than glatiramer acetate or another interferon beta); or
• 3.Participated in CAMMS223.
• NOTE: Criteria 1 and 2 above meant that participants who enrolled in CAMMS323 or CAMMS324 but did not complete the 2-year study period or went on to receive non-study drug DMTs after randomization were not eligible for inclusion in the Extension Study. Participants who enrolled in CAMMS324 after participation in CAMMS223 must meet criteria 1 or 2 to be eligible for inclusion in the Extension Study.

Exclusion Criteria:

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

Contacts and Locations

Locations

United States, Alabama

North Central Neurology Associates, P.C.

Cullman, Alabama, United States

United States, Arizona

HOPE Research Institute

Phoenix, Arizona, United States

St. Joseph's Hospital and Medical Center Barrow Neurology Clinics - Barrow Neurological Institute

Phoenix, Arizona, United States

Mayo Clinic Arizona (Scottsdale)

Scottsdale, Arizona, United States

Northwest NeuroSpecialists, PLLC

Tucson, Arizona, United States

United States, California

East Bay Physicians Medical Group/ Sutter East Bay Medical Foundation

Berkeley, California, United States

Neurology Center North Orange County

La Habra, California, United States

University of Southern California Keck School of Medicine/University of Southern California LAC & USC Medical Center

Los Angeles, California, United States

Neuro-Therapeutics, Inc.

Pasadena, California, United States

Stanford University Medical Center

Stanford, California, United States

United States, Colorado

University of Colorado Health Science Center - Aurora

Aurora, Colorado, United States

Advanced Neurology of Colorado

Fort Collins, Colorado, United States

United States, Connecticut

Yale MS Research Center

New Haven, Connecticut, United States

United States, District of Columbia

The George Washington University Medical Faculty Associates

Washington, D.C., District of Columbia, United States

United States, Florida

University of Florida Neuroscience Institute

Jacksonville, Florida, United States

Neurology Associates, P.A.

Maitland, Florida, United States

Neurological Associates

Pompano Beach, Florida, United States

Negroski, Stein, Sutherland and Hanes Neurology

Sarasota, Florida, United States

Axiom Clinical Research of Florida

Tampa, Florida, United States

University of South Florida College of Medicine

Tampa, Florida, United States

United States, Georgia

Emory University Department of Neurology

Atlanta, Georgia, United States

Shepherd Center Multiple Sclerosis Institute

Atlanta, Georgia, United States

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States

Consultants in Neurology, LTD

Northbrook, Illinois, United States

United States, Indiana

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Indiana University Multiple Sclerosis Center

Indianapolis, Indiana, United States

United States, Iowa

Iowa Health Physicians

Des Moines, Iowa, United States

Ruan Neurology Clinic and Clinical Research Center, Mercy Medical Center

Des Moines, Iowa, United States

United States, Kansas

University of Kansas Medical Center, Department of Neurology

Kansas City, Kansas, United States

MidAmerica Neuroscience Institute

Lenexa, Kansas, United States

United States, Kentucky

Associates in Neurology, P.S.C.

Lexington, Kentucky, United States

Kentucky Neuroscience Research

Louisville, Kentucky, United States

United States, Maryland

University of Maryland, Maryland Center for MS

Baltimore, Maryland, United States

United States, Massachusetts

The MS Center at St. Elizabeth's

Boston, Massachusetts, United States

UMass Memorial Medical Center

Worcester, Massachusetts, United States

United States, Michigan

University of Michigan Medical School

Ann Arbor, Michigan, United States

Michigan Neurology Association

Clinton, Michigan, United States

Wayne State University, The School of Medicine, Department of Neurology

Detroit, Michigan, United States

Spectrum Health Medical Group, Neurology/Michigan Medical P.C., West Michigan MS Clinic

Grand Rapids, Michigan, United States

Northern Michigan Neurology

Traverse City, Michigan, United States

United States, Missouri

Saint Luke's Brain & Stroke Institute

Kansas City, Missouri, United States

United States, Nevada

Renown Institute for Neurosciences

Reno, Nevada, United States

United States, New Hampshire

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

United States, New Jersey

MS Center at Holy Name Hospital

Teaneck, New Jersey, United States

United States, New Mexico

University of New Mexico, Dept. of Neurology

Albuquerque, New Mexico, United States

United States, New York

Empire Neurology P.C.

Latham, New York, United States

Winthrop University Hospital Multiple Sclerosis Treatment Center

Mineola, New York, United States

MS Care Center at NYUMC and HJD

New York, New York, United States

The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai

New York, New York, United States

South Shore Neurologic Associates, P.C.

Patchogue, New York, United States

Rochester Multiple Sclerosis Center

Rochester, New York, United States

SUNY Upstate Medical University, Department of Neurology

Syracuse, New York, United States

United States, North Carolina

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Wake Forest University Health Science Department of Neurology

Winston-Salem, North Carolina, United States

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Oak Clinic for Multiple Sclerosis

Uniontown, Ohio, United States

United States, Oklahoma

OMRF Multiple Sclerosis Center of Excellence

Oklahoma City, Oklahoma, United States

United States, Pennsylvania

Lehigh Valley Hospital Neurosciences and Pain Research

Allentown, Pennsylvania, United States

United States, Rhode Island

Rhode Island Hospital MS Center - The Neurology Foundation, Inc

Providence, Rhode Island, United States

United States, Tennessee

Neurology Clinic PC

Cordova, Tennessee, United States

Advanced Neurosciences Institute

Franklin, Tennessee, United States

Hope Neurology

Knoxville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

United States, Texas

Baylor College of Medicine, Maxine Mesinger MS Clinic

Houston, Texas, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

Integra Clinical Research

San Antonio, Texas, United States

Neurology Center of San Antonio

San Antonio, Texas, United States

United States, Virginia

MS Center of Greater Washington

Vienna, Virginia, United States

United States, Washington

Swedish Medical MS Center

Seattle, Washington, United States

Argentina

DIABAID

Buenos Aires, Argentina

Australia, New South Wales

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Southern Neurology

Kogarah, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Australia, Queensland

Gold Coast Hospital

Southport, Queensland, Australia

Australia, Tasmania

Royal Hobart Hospital

Hobart, Tasmania, Australia

Australia, Victoria

St. Vincent's Hospital

Fitzroy, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Australia

The Wesley Research Institute

Auchenflower QLD, Australia

The Queen Elizabeth Hospital

Woodville, SA, Australia

Austria

AKH Wien-Universitätskliniken für Neurologie

Vienna, Austria

Belgium

Cliniques Universitaires Saint-luc

Brussel, Belgium

CHU Ourthe Amblève

Esneux, Belgium

University Hospital Leuven, Campus Gasthuisberg

Leuven, Belgium

Brazil

Hospital Mae de Deus

Porto Alegre, Brazil

Hospital da Restauração, Neurology department

Recife, PE, Brazil

Irmandade da Santa Casa de Misericórdio de São Paulo, Neurology department

São Paulo, SP, Brazil

Hospital das Clínicas da Faculdade de Medicina da USP, Neurology department

São Paulo,SP, Brazil

Canada, Alberta

University of Calgary, Department of Neurology

Calgary, Alberta, Canada

Canada, Ontario

Kingston General Hospital MS Clinic

Kingston, Ontario, Canada

Canada, Quebec

Clinique Neuro-Outaouais

Gatineau, Quebec, Canada

Recherche Sepmus, Inc.

Greenfield Park, Quebec, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Canada

London Health Sciences Centre - University Hospital

London, ON, Canada

The Ottawa Hospital - MS Research

Ottawa, Ontario, Canada

University of British Columbia

Vancouver, BC, Canada

Croatia

Clinical Hospital Osijek

Osijek, Croatia

Clinical Hospital Centre Rijeka

Rijeka, Croatia

General Hospital Varazdin, Department for Neurology

Varazdin, Croatia

Clinical Hospital Centre "Sestre Milosrdnice"

Zagreb, Croatia

Clinical Hospital Centre Zagreb

Zagreb, Croatia

Clinical Hospital Sveti Duh

Zagreb, Croatia

Czechia

St. Anne's University Hospital Brno

Brno, Czechia

University Hospital Hradec Králové

Hradec Kralove, Czechia

General Hospital, 128 21 Praha 2

Prague, Czechia

Hospital Teplice, Neurology Department, MS centrum

Teplice, Czechia

Denmark

Rigshospitalet Department of Neurology

Copenhagen, Denmark

Aarhus Sygehus

Århus C, Denmark

France

Hôpital Général

Dijon Cedex, France

Groupe Hospitalier Pitié-Salpêtrière, Fédération de Maladies du System Nerveux Central

Paris Cedex 13, France

CHU Pontchaillou

Rennes Cedex 9, France

Hôpital Civil

Strasbourg Cedex, France

CHU de Toulouse, Hôpital Purpan

Toulouse Cedex 9, France

Germany

Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn

Bonn, DE, Germany

Jüdisches Krankenhaus Berlin

Berlin-Mitte, Germany

Universitätsklinik Carl Gustav Carus Dresden

Dresden, Germany

Klinikum der JW Goethe Universität

Frankfurt am Main, Germany

Asklepios Klinik Barmbek

Hamburg, Germany

Medizinische Hochschule Hannover

Hannover, Germany

Oberhavel Klinicum GmbH - Krankenhaus Hennigsdorf

Hennigsdorf, Germany

Klinikum Ingolstadt

Ingolstadt, Germany

Klinikum rechts der Isar

München, Germany

Medizinische Fakultät der Universität Rostock,Zentrum für Nervenheilkunde

Rostock, Germany

Universitätsklinikum Ulm, Klinik für Neurologie im RKU

Ulm, Germany

Fachkrankenhaus Hubertusburg GmbH, Klinik für Neurologie und Neurologische Intensivmedizin

Wermsdorf, Germany

Israel

Hadassah Medical Center Ein Karem

Ein Karem, Jerusalem, Israel

Sheba Medical Center

Ramat Gan, Israel

Sourasky Tel Aviv Medical Center

Tel Aviv, Israel

Italy

Università di Cagliari

Cagliari, Italy

Ospedale S. Antonio Abate di Gallarate

Gallarate (Varese), Italy

Ospedale S. Luigi Gonzaga

Orbassano (TO), Italy

Universita Degli Studi di Roma "La Sapienza"

Roma, Italy

Mexico

Unidad de Investigación en Salud

Chihuahua, CHH, Mexico

Medica Sur

Mexico City, DFE, Mexico

Netherlands

Jeroen Bosch Ziekenhuis

Den Bosch, Netherlands

Orbis Medisch Concern

Sittard-Geleen, Netherlands

Poland

Centrum Neurologii Klinicznej Sp. Zo.o.

Krakow, Poland

Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Kliniczny Nr1 im. Norberta Barlickiego

Lodz, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, Poland

Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Med. im. Karola Marcinkowskiego w Poznaniu

Poznan, Poland

Institute of Psychiatry and Neurology/Instytut Psychiatrii i Neurologii

Warsaw, Poland

Russian Federation

Research Medical Complex "Your Health" Ltd

Kazan, Russian Federation

Moscow State Public Medical Institution Clinical Hospital #11, Neurology Department

Moscow, Russian Federation

Neurology Research Center under the Russian Academy of Medical Sciences

Moscow, Russian Federation

Russian State Medical University, Department of Neurology and Neurosurgery

Moscow, Russian Federation

Municipal Treatment and Prevention Institution, City Hospital #33

Nizhny Novgorod, Russian Federation

Federal State Public Medical Institution: Siberian District Medical Center under the Federal Agency

Novosibirsk, Russian Federation

Municipal Public Medical Institution: City Hospital #2 of Pyatigorsk, Neurology Department

Pyatigorsk, Russian Federation

Samara Regional Clinical Hospital n.a. Kalinin

Samara, Russian Federation

Institute of Human Brain RAS, Laboratory of Neuroimmunology

St. Petersburg, Russian Federation

St Petersburg State Pavlov Medical University, Dept of Neurology and Neurosurgery with a Hospital

St. Petersburg, Russian Federation

St. Petersburg General Hospital #2, Neurology Department #2

St. Petersburg, Russian Federation

St. Petersburg State Public Medical Institution: Nikolayevskaya Hospital

St. Petersburg, Russian Federation

State Public Medical Institution: Republican Clinical Hospital n.a. G.G. Kuvatov

Ufa, Russian Federation

Serbia

Clinical Centre Serbia, Institute of Neurology,Dr.Subotica 6,Belgrade

Belgrade, Serbia

Military Medical Academy, Institute of Neurology

Belgrade, Serbia

Clinical Centre Kragujevac, Clinic of Neurology

Kragujevac, Serbia

Clinical Centre Nis, Clinic of Neurology

Nis, Serbia

Clinical Centre Vojvodina

Novi Sad, Serbia

Spain

Hospital Universitario Vall d' Hebron

Barcelona, Spain

Hospital Clínico Universitario San Carlos

Madrid, Spain

Hospital Carlos Haya, Neurology Service

Málaga, Spain

Hospital Virgen Macarena

Seville, Spain

Sweden

SU/Östra sjukhuset

Göteborg, Sweden

Norrlands Universitets sjukhus

Umeå, Sweden

Ukraine

Institute of Neurology, Psychiatry and Narcology under the AMS of Ukraine, Dep of Neuroinfection& MS

Kharkov, Ukraine

Hospital of Directorate of the Medical Corps within the Ukrainian Security Service, Neurology Dept.

Kiev-21, Ukraine

Kiev Municipal Clinical Hospital #4, Department of Demyelinating Diseases of the Nervous System

Kiev, Ukraine

Lviv National Medical University n.a. Danylo Galytsky, Department of Neurology

Lviv, Ukraine

United Kingdom

Frenchay Hospital

Bristol, United Kingdom

Addenbrookes Hospital

Cambridge, United Kingdom

University Hospital of Wales, Dept of Neurology

Cardiff, United Kingdom

Royal London Hospital

London, United Kingdom

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Royal Hallamshire Hospital

Sheffield, United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Bayer

Investigators

• Study Director: Medical Monitor; Genzyme Coorporation

More Information

Publications:

CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.

Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.

Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):

Multiple Sclerosis

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Alemtuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents