ClinicalTrials.gg
Sign In
CompletedNCT00930553Updated May 15, 2017Results posted

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

A Phase 3 interventional study of alemtuzumab in Multiple Sclerosis, Relapsing-Remitting, sponsored by Genzyme, a Sanofi Company. Completed at 176 sites in 23 countries. Per ClinicalTrials.gov, last updated 2017-05-15.

Sponsored by Genzyme, a Sanofi Company (part of Sanofi) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,314
Allocation
Non-randomized
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

  • Multiple Sclerosis, Relapsing-Remitting

Keywords

  • Multiple Sclerosis
03

In context

Multiple Sclerosis, Relapsing-Remitting

615 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 80 are open to participants now.

This study's enrollment of 1,314 is above the median of 72 across 437 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.

Browse Multiple Sclerosis, Relapsing-Remitting studies →

Lead sponsor

Genzyme, a Sanofi Company is the lead sponsor of 308 studies on the registry; 5 are open to participants now.

Of its 25 completed or terminated interventional studies of FDA-regulated products, 19 (76%) have results posted.

First submitted before Genzyme became part of Sanofi.

Browse Genzyme studies →All Sanofi studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
1,314 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • Biologicalalemtuzumab

    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.

06

What researchers measure

Primary outcomes

  1. Annualized Relapse Rate (ARR)

    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.

    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)

  2. Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab

    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

  3. Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment

    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.

    Time frame: Year 1 prior to retreatment, Year 1, 2, 3 after retreatment

  4. Number of Participants With Sustained Accumulation of Disability (SAD)

    SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.

    Time frame: Baseline (Year 0) up to Year 6

  5. Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison

    SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

Secondary outcomes

  1. Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6

    SRD was defined as a ≥1 point decrease in EDSS score lasting \>= 6 months. SRD is only applicable to participants with a baseline EDSS score of \>= 2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.

    Time frame: Baseline (Year 0) up to Year 6

  2. Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study

    SRD was defined as a \>=1 point decrease in EDSS score lasting \>=6 months. SRD is only applicable to participants with a baseline EDSS score of ≥2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Extension study (CAMMS03409) baseline up to Extension Year 2

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

    EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 \[NCT00530348\] or CAMMS324 \[NCT00548405\]) value from EDSS scores at specified time points.

    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

  4. Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison

    EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

  5. Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment

    EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.

    Time frame: Retreatment baseline, Year 1, 2 and 3 after retreatment baseline

  6. Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity

    Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.

    Time frame: Year 3, 4, 5 and 6

  7. Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment

    Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

  8. Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment

    Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.

    Time frame: Retreatment Baseline, Year 1, 2 and 3 after retreatment

  9. Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6

    Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.

    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

  10. Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity

    Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.

    Time frame: Year 3, 4, 5 and 6

  11. Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6

    Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.

    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

  12. Percentage of Relapse Free Participants

    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.

    Time frame: Year 3, 4, 5 and 6

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

    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

    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

  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

    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

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

    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

    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

  16. Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison

    SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

  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

    FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.

    Time frame: Baseline (Month 0 of CAMMS323 and Month 0 of CAMMS324 for "Alemtuzumab Treatment CAMMS323 Extension" group and "Alemtuzumab Treatment CAMMS324 Extension" group, respectively), Year 3, 4, 5, 6

  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

    FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

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

    EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.

    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

  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

    EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

    Time frame: Baseline (Year 0 of initial studies) up to Year 4

07

Results

Posted May 15, 2017

Participant flow

This extension study enrolled participants from previous 3 studies: CAMMS223 (NCT00050778), CAMMS323 (NCT00530348), and CAMMS324 (NCT00548405). Participants were enrolled in this study only after their Month 24 visit in CAMMS323 and CAMMS324. CAMMS223 participants were enrolled within 6 months once their site received approval of extension study.

Participant flow — Overall Study
MilestoneAlemtuzumab
Started1314
Participants entered from camms223141
Participants entered from camms323488
Participants entered from camms324685
Completed1091
Not completed223
Withdrew: Adverse event1
Withdrew: Lack of efficacy7
Withdrew: Physician decision39
Withdrew: Protocol violation1
Withdrew: Pregnancy1
Withdrew: Withdrawal by subject88
Withdrew: Lost to follow-up25
Withdrew: Death9
Withdrew: Study terminated by sponsor24
Withdrew: Other than specified above28

Outcome measures

PrimaryAnnualized Relapse Rate (ARR)

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis (MS) that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation.

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)
Reported as:
Number · relapses per participant per year
Annualized Relapse Rate (ARR)
relapses per participant per yearAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Year 30.190.22
Year 40.160.24
Year 50.150.19
Year 60.120.16
PrimaryAnnualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through repeated negative binomial regression with robust variance estimation and covariate adjustment for geographic region. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Number · relapses per participant per year
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab
relapses per participant per yearIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab0.42 (0.28 to 0.64)0.14 (0.09 to 0.21)0.60 (0.45 to 0.78)0.15 (0.10 to 0.22)
PrimaryAnnualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability. ARR was obtained from the total number of confirmed relapses that occurred during the treatment follow-up time of all participants divided by the sum of total follow-up time of all participants involved in certain treatment groups. ARR was estimated through negative binomial regression with robust variance estimation without covariate adjustment.

Time frame:
Year 1 prior to retreatment, Year 1, 2, 3 after retreatment
Reported as:
Number · relapses per participant per year
Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment
relapses per participant per yearAlemtuzumab Retreatment
Year 1 prior to retreatment0.79 (0.73 to 0.87)
Year 1 after retreatment0.18 (0.14 to 0.24)
Year 2 after retreatment0.29 (0.23 to 0.38)
Year 3 after retreatment0.30 (0.21 to 0.41)
PrimaryNumber of Participants With Sustained Accumulation of Disability (SAD)

SAD: defined as an increase of at least 1.5 points in Expanded Disability Status Scale (EDSS) score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD was estimated by Kaplan-Meier method and reported in this outcome measure. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "alemtuzumab treatment CAMMS323 extension" group and "alemtuzumab Treatment CAMMS324 Extension" group, respectively.

Time frame:
Baseline (Year 0) up to Year 6
Reported as:
Count of participants · Participants
Number of Participants With Sustained Accumulation of Disability (SAD)
ParticipantsAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Number of Participants With Sustained Accumulation of Disability (SAD)79118
Statistical analysis
  • Alemtuzumab Treatment CAMMS323 Extension · Percentage with sad: 22.33 · 95% CI 18.33 to 27.06The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
  • Alemtuzumab Treatment CAMMS324 Extension · Percentage with sad: 29.69 · 95% CI 25.42 to 34.49The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
PrimaryNumber of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison

SAD: defined as an increase of at least 1.5 points in EDSS score for participants with prior study baseline score of 0 and increase of at least 1.0 point for participants with a prior study baseline score of 1.0 or more; and the increase persisted over a 6-month consecutive period. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) and ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), higher scores indicating worse neurological function. Number of participants with SAD over 2 years before and 2 years after alemtuzumab treatment were estimated by Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Count of participants · Participants
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison
ParticipantsIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison13112917
Statistical analysis
  • IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab) · Percentage with sad: 9.35 · 95% CI 5.54 to 15.56The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
  • IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab) · Percentage with sad: 7.95 · 95% CI 4.48 to 13.90The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
  • IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab) · Percentage with sad: 20.42 · 95% CI 14.67 to 28.03The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
  • IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab) · Percentage with sad: 11.99 · 95% CI 7.63 to 18.58The percentage and 95% CI of the participants with SAD are estimated by the Kaplan Meier method.
SecondaryNumber of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6

SRD was defined as a ≥1 point decrease in EDSS score lasting \>= 6 months. SRD is only applicable to participants with a baseline EDSS score of \>= 2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 6 was estimated using Kaplan-Meier method and reported in this outcome measure.

Time frame:
Baseline (Year 0) up to Year 6
Reported as:
Count of participants · Participants
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6
ParticipantsAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 674130
Statistical analysis
  • Alemtuzumab Treatment CAMMS323 Extension · Percentage with srd: 32.69 · 95% CI 26.96 to 39.28The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.
  • Alemtuzumab Treatment CAMMS324 Extension · Percentage with srd: 42.46 · 95% CI 37.08 to 48.28The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.
SecondaryNumber of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study

SRD was defined as a \>=1 point decrease in EDSS score lasting \>=6 months. SRD is only applicable to participants with a baseline EDSS score of ≥2.0. EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Number of participants with SRD at Year 2 of CAMMS03409 was estimated using Kaplan-Meier method and reported in this outcome measure. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Extension study (CAMMS03409) baseline up to Extension Year 2
Reported as:
Count of participants · Participants
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study
ParticipantsIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study1114
Statistical analysis
  • IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab) · Percentage with srd: 16.92 · 95% CI 9.75 to 28.47The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.
  • IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab) · Percentage with srd: 13.89 · 95% CI 8.47 to 22.33The percentage and 95% CI of the participants with SRD are estimated by the Kaplan Meier method.
SecondaryChange From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 \[NCT00530348\] or CAMMS324 \[NCT00548405\]) value from EDSS scores at specified time points.

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
Reported as:
Mean · units on a scale
Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6
units on a scaleAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 3-0.08 (-0.20 to 0.04)-0.02 (-0.14 to 0.10)
Change at Year 4-0.06 (-0.19 to 0.07)0.06 (-0.07 to 0.19)
Change at Year 50.06 (-0.08 to 0.19)0.13 (-0.01 to 0.27)
Change at Year 60.09 (-0.04 to 0.23)0.18 (0.03 to 0.32)
SecondaryChange From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting baseline (Month 0 of the study CAMMS323 or CAMMS324 for pre alemtuzumab period or CAMMS03409 baseline for post alemtuzumab period) value, from EDSS scores at specified time points. The IFNB-1a/Alemtuzumab switch pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting groups. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323 participants" and "CAMMS324 participants" respectively.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Mean · units on a scale
Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison
units on a scaleIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Year 0 - 2-0.15 (-0.32 to 0.03)-0.07 (-0.23 to 0.09)0.11 (-0.05 to 0.26)-0.02 (-0.18 to 0.14)
Year 3 - 4-0.21 (-0.43 to 0.00)0.08 (-0.11 to 0.27)0.20 (-0.01 to 0.41)0.13 (-0.05 to 0.31)
SecondaryChange From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses the 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicate worse neurological function. Change was calculated by subtracting retreatment baseline (annual visit prior to the retreatment start date) value from EDSS scores at specified time points.

Time frame:
Retreatment baseline, Year 1, 2 and 3 after retreatment baseline
Reported as:
Mean · units on a scale
Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment
units on a scaleAlemtuzumab Retreatment
Retreatment baseline2.89 ± 1.514
Change at Year 1 after retreatment baseline-0.22 ± 1.033
Change at Year 2 after retreatment baseline-0.13 ± 1.109
Change at Year 3 after retreatment baseline0.07 ± 1.356
SecondaryPercentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity

Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually.

Time frame:
Year 3, 4, 5 and 6
Reported as:
Number · percentage of participants
Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity
percentage of participantsAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Year 372.668.8
Year 470.370.2
Year 570.267.0
Year 666.869.6
SecondaryPercentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment

Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Number · percentage of participants
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment
percentage of participantsIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Year 0 - 15779.344.663.8
Year 0 - 260.781.847.581.7
SecondaryPercentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment

Analysis of new or enlarging lesions that appear hyperintense on T2-weighted MRI scans performed annually. Retreatment baseline was the annual visit prior to the retreatment start date.

Time frame:
Retreatment Baseline, Year 1, 2 and 3 after retreatment
Reported as:
Number · percentage of participants
Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment
percentage of participantsAlemtuzumab Retreatment
Retreatment baseline49.2
Year 1 after retreatment baseline64.1
Year 2 after retreatment baseline66.0
Year 3 after retreatment baseline60.2
SecondaryPercentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6

Lesion volume was quantitatively assessed by hyperintensity on T2-weighted MRI scans.

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
Reported as:
Mean · percent change
Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6
percent changeAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 3-6.57 ± 29.961.69 ± 31.62
Change at Year 4-5.04 ± 32.884.97 ± 41.11
Change at Year 5-4.09 ± 36.9912.37 ± 80.74
Change at Year 6-2.68 ± 42.9211.46 ± 73.91
SecondaryPercentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity

Analysis of new gadolinium-enhancing lesions that appear on MRI scans performed annually. Baseline was the prior annual visit.

Time frame:
Year 3, 4, 5 and 6
Reported as:
Number · percentage of participants
Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity
percentage of participantsAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Year 390.686.5
Year 487.188.8
Year 587.589.4
Year 686.790.0
SecondaryPercent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6

Brain parenchymal fraction (calculated as the ratio of brain parenchymal volume to total intradural volume), is a sensitive indicator of brain atrophy.

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
Reported as:
Mean · percent change
Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6
percent changeAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 3-1.068 ± 1.185-0.761 ± 1.240
Change at Year 4-1.251 ± 1.228-0.949 ± 1.341
Change at Year 5-1.437 ± 1.317-0.983 ± 1.374
Change at Year 6-1.601 ± 1.370-1.051 ± 1.472
SecondaryPercentage of Relapse Free Participants

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to MS that last for at least 48 hours, present at normal body temperature, and that were preceded by at least 30 days of clinical stability.

Time frame:
Year 3, 4, 5 and 6
Reported as:
Number · percentage of participants
Percentage of Relapse Free Participants
percentage of participantsAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Year 384.1480.56
Year 486.8479.27
Year 587.3583.29
Year 688.9686.86
SecondaryChange From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

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
Reported as:
Mean · units on a scale
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6
units on a scaleAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 31.90 (0.85 to 2.95)1.72 (0.84 to 2.60)
Change at Year 42.15 (1.10 to 3.20)1.34 (0.40 to 2.28)
Change at Year 51.85 (0.75 to 2.94)1.34 (0.39 to 2.29)
Change at Year 61.65 (0.56 to 2.74)1.00 (-0.03 to 2.03)
SecondaryChange From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of first four health aspects (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Mean · units on a scale
Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison
units on a scaleIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Year 11.16 (-0.48 to 2.81)2.00 (0.43 to 3.57)0.79 (-0.34 to 1.93)1.56 (0.38 to 2.75)
Year 21.20 (-0.54 to 2.95)0.41 (-1.21 to 2.04)0.45 (-0.86 to 1.76)1.31 (0.14 to 2.48)
SecondaryChange From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

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
Reported as:
Mean · units on a scale
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6
units on a scaleAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 32.43 (1.07 to 3.78)1.96 (0.85 to 3.07)
Change at Year 43.17 (1.85 to 4.49)1.91 (0.77 to 3.05)
Change at Year 52.54 (1.23 to 3.85)1.75 (0.59 to 2.92)
Change at Year 62.41 (1.01 to 3.80)1.58 (0.35 to 2.82)
SecondaryChange From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: 1) physical functioning, 2) role physical, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) role emotional and 8) mental health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of last four health aspects (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group. Baseline was defined as Year 0 of CAMMS323 and Year 0 of CAMMS324 for "CAMMS323" and "CAMMS324" participants, respectively.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Mean · units on a scale
Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison
units on a scaleIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Change at Year 12.88 (0.49 to 5.27)1.98 (-0.46 to 4.43)1.83 (0.30 to 3.36)1.21 (-0.31 to 2.74)
Change at Year 22.32 (-0.11 to 4.74)2.08 (-0.38 to 4.54)1.65 (0.05 to 3.25)1.65 (-0.01 to 3.31)
SecondaryChange From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6

FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life.

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
Reported as:
Mean · units on a scale
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
units on a scaleAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 35.28 (2.03 to 8.52)4.55 (1.89 to 7.21)
Change at Year 46.81 (3.55 to 10.08)3.65 (0.98 to 6.32)
Change at Year 54.82 (1.55 to 8.10)3.57 (0.78 to 6.37)
Change at Year 64.40 (1.03 to 7.78)3.16 (0.07 to 6.25)
SecondaryChange From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison

FAMS is a widely accepted, MS-specific, quality of life questionnaire. It comprised of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Participants provided their response based on the recall of past week. Each item was rated on a 5-point scale ranges from 0 (poor) to 4 (best), where higher scores indicated higher/better quality of life. Scores from 44 calculable items were summed to provide FAMS total score. FAMS total score ranges from 0 (poor) to 176 (best), where higher scores indicated higher/better quality of life. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Mean · units on a scale
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
units on a scaleIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre AlemtuzumabIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Change at Year 14.27 (-1.17 to 9.72)4.82 (0.10 to 9.53)3.19 (-0.12 to 6.51)5.83 (2.74 to 8.92)
Change at Year 21.88 (-3.63 to 7.38)3.10 (-2.16 to 8.35)0.93 (-2.86 to 4.71)4.66 (1.07 to 8.24)
SecondaryChange From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6

EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement.

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
Reported as:
Mean · units on a scale
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6
units on a scaleAlemtuzumab Treatment CAMMS323 ExtensionAlemtuzumab Treatment CAMMS324 Extension
Change at Year 33.505 (1.438 to 5.572)2.859 (1.008 to 4.710)
Change at Year 45.144 (3.078 to 7.210)2.992 (1.145 to 4.838)
Change at Year 54.409 (2.303 to 6.515)3.034 (1.169 to 4.898)
Change at Year 64.134 (1.946 to 6.323)3.155 (0.933 to 5.377)
SecondaryChange From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison

EQ-5D is a standardized instrument for measuring health status consisting of EQ-5D descriptive system and VAS. The EQ-5D VAS range is from 0-100, higher scores indicate a better health state and a positive change indicates improvement. The IFNB-1a/Alemtuzumab switch from CAMMS323 or CAMMS324 to CAMMS03409 pre alemtuzumab reporting group consisted of the same participants as those in the corresponding post alemtuzumab reporting group.

Time frame:
Baseline (Year 0 of initial studies) up to Year 4
Reported as:
Mean · units on a scale
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison
units on a scaleIFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS323/03409 (Post Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Pre Alemtuzumab)IFNB-1a/Alemtuzumab Switch CAMMS324/03409 (Post Alemtuzumab)
Change at Year 14.165 (0.639 to 7.691)4.576 (1.419 to 7.733)1.663 (-0.893 to 4.219)4.337 (1.614 to 7.059)
Change at Year 22.359 (-1.319 to 6.037)4.515 (1.407 to 7.622)-0.712 (-3.552 to 2.129)3.346 (0.324 to 6.368)

Adverse events

Collected over All Adverse Events (AE) were collected from signature of the informed consent form in the extension study up to the end of extension study visit (up to Year 6) regardless of seriousness or relationship to investigational product.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alemtuzumab—376/1,314 (28.6%)1,225/1,314 (93.2%)
Most frequent serious events
Showing 10 of 343
Most frequent serious events
EventAlemtuzumab
Multiple sclerosis relapseNervous system disorders67/1314
Basedow's diseaseEndocrine disorders39/1314
Immune thrombocytopenic purpuraBlood and lymphatic system disorders16/1314
HyperthyroidismEndocrine disorders14/1314
PneumoniaInfections and infestations13/1314
Abdominal painGastrointestinal disorders11/1314
Herpes zosterInfections and infestations10/1314
SyncopeNervous system disorders9/1314
SepsisInfections and infestations8/1314
NauseaGastrointestinal disorders7/1314
Most frequent other events
Showing 10 of 56
Most frequent other events
EventAlemtuzumab
Multiple sclerosis relapseNervous system disorders508/1314
HeadacheNervous system disorders437/1314
NasopharyngitisInfections and infestations382/1314
Urinary tract infectionInfections and infestations360/1314
FatigueGeneral disorders280/1314
Upper respiratory tract infectionInfections and infestations272/1314
InsomniaPsychiatric disorders231/1314
PyrexiaGeneral disorders228/1314
ArthralgiaMusculoskeletal and connective tissue disorders216/1314
RashSkin and subcutaneous tissue disorders208/1314

Baseline characteristics

Age, Continuous
Age, Continuous(years)Alemtuzumab
Mean36.7 ± 8.51
Sex: Female, Male
Sex: Female, Male(Participants)Alemtuzumab
Female857
Male457
08

Study locations

176 sites
  • North Central Neurology Associates, P.C.
    Cullman, Alabama, United States
  • 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
  • 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
  • University of Colorado Health Science Center - Aurora
    Aurora, Colorado, United States
  • Advanced Neurology of Colorado
    Fort Collins, Colorado, United States
  • Yale MS Research Center
    New Haven, Connecticut, United States
  • The George Washington University Medical Faculty Associates
    Washington D.C., District of Columbia, United States
  • 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
  • Emory University Department of Neurology
    Atlanta, Georgia, United States
  • Shepherd Center Multiple Sclerosis Institute
    Atlanta, Georgia, United States
  • University of Chicago Medical Center
    Chicago, Illinois, United States
  • Consultants in Neurology, LTD
    Northbrook, Illinois, United States
  • Fort Wayne Neurological Center
    Fort Wayne, Indiana, United States
  • Indiana University Multiple Sclerosis Center
    Indianapolis, Indiana, United States
  • Iowa Health Physicians
    Des Moines, Iowa, United States
  • Ruan Neurology Clinic and Clinical Research Center, Mercy Medical Center
    Des Moines, Iowa, United States
  • University of Kansas Medical Center, Department of Neurology
    Kansas City, Kansas, United States
  • MidAmerica Neuroscience Institute
    Lenexa, Kansas, United States
  • Associates in Neurology, P.S.C.
    Lexington, Kentucky, United States
  • Kentucky Neuroscience Research
    Louisville, Kentucky, United States
  • University of Maryland, Maryland Center for MS
    Baltimore, Maryland, United States
  • The MS Center at St. Elizabeth's
    Boston, Massachusetts, United States
  • UMass Memorial Medical Center
    Worcester, Massachusetts, United States
  • 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
  • Saint Luke's Brain & Stroke Institute
    Kansas City, Missouri, United States
  • Renown Institute for Neurosciences
    Reno, Nevada, United States
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire, United States
  • MS Center at Holy Name Hospital
    Teaneck, New Jersey, United States
  • University of New Mexico, Dept. of Neurology
    Albuquerque, New Mexico, United States
  • 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
  • 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
  • Cleveland Clinic Foundation
    Cleveland, Ohio, United States
  • Oak Clinic for Multiple Sclerosis
    Uniontown, Ohio, United States
  • OMRF Multiple Sclerosis Center of Excellence
    Oklahoma City, Oklahoma, United States
  • Lehigh Valley Hospital Neurosciences and Pain Research
    Allentown, Pennsylvania, United States
  • Rhode Island Hospital MS Center - The Neurology Foundation, Inc
    Providence, Rhode Island, United States
  • 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
  • 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
  • MS Center of Greater Washington
    Vienna, Virginia, United States
  • Swedish Medical MS Center
    Seattle, Washington, United States
  • DIABAID
    Buenos Aires, Argentina
  • 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
  • Gold Coast Hospital
    Southport, Queensland, Australia
  • Royal Hobart Hospital
    Hobart, Tasmania, Australia
  • St. Vincent's Hospital
    Fitzroy, Victoria, Australia
  • Austin Health
    Heidelberg, Victoria, Australia
  • Royal Melbourne Hospital
    Parkville, Victoria, Australia
  • The Wesley Research Institute
    Auchenflower QLD, Australia
  • The Queen Elizabeth Hospital
    Woodville, SA, Australia
  • AKH Wien-Universitätskliniken für Neurologie
    Vienna, Austria
  • Cliniques Universitaires Saint-luc
    Brussels, Belgium
  • CHU Ourthe Amblève
    Esneux, Belgium
  • University Hospital Leuven, Campus Gasthuisberg
    Leuven, Belgium
  • 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
  • University of Calgary, Department of Neurology
    Calgary, Alberta, Canada
  • Kingston General Hospital MS Clinic
    Kingston, Ontario, Canada
  • Clinique Neuro-Outaouais
    Gatineau, Quebec, Canada
  • Recherche Sepmus, Inc.
    Greenfield Park, Quebec, Canada
  • Hopital Maisonneuve-Rosemont
    Montreal, Quebec, 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
  • Clinical Hospital Osijek
    Osijek, Croatia
  • Clinical Hospital Centre Rijeka
    Rijeka, Croatia
  • General Hospital Varazdin, Department for Neurology
    Varaždin, Croatia

Showing the first 100 of 176 sites across 23 countries.

09

References and documents

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. PubMed 18946064 ↗
  • 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. PubMed 23122652 ↗
  • 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. PubMed 23122650 ↗
  • Ziemssen T, Bass AD, Van Wijmeersch B, Eichau S, Richter S, Hoffmann F, Armstrong NM, Chirieac M, Cunha-Santos J, Singer BA. Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study. Ther Adv Neurol Disord. 2025 Feb 10;18:17562864241306575. doi: 10.1177/17562864241306575. eCollection 2025. PubMed 39935588 ↗
  • Coles AJ, Achiron A, Traboulsee A, Singer BA, Pozzilli C, Oreja-Guevara C, Giovannoni G, Comi G, Freedman MS, Ziemssen T, Shiota D, Rawlings AM, Wong AT, Chirieac M, Montalban X. Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study. Ther Adv Neurol Disord. 2023 Sep 21;16:17562864231194823. doi: 10.1177/17562864231194823. eCollection 2023. PubMed 37745914 ↗
  • Dayan CM, Lecumberri B, Muller I, Ganesananthan S, Hunter SF, Selmaj KW, Hartung HP, Havrdova EK, LaGanke CC, Ziemssen T, Van Wijmeersch B, Meuth SG, Margolin DH, Poole EM, Baker DP, Senior PA. Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies. Mult Scler J Exp Transl Clin. 2023 Jan 3;9(1):20552173221142741. doi: 10.1177/20552173221142741. eCollection 2023 Jan-Mar. PubMed 36619856 ↗
  • 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. PubMed 34882037 ↗
  • 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. PubMed 34378446 ↗
  • 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. PubMed 34035833 ↗
  • 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. PubMed 33476880 ↗
  • 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. PubMed 33414927 ↗
  • 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. PubMed 32710396 ↗
  • 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. PubMed 32539719 ↗
  • 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. PubMed 31762387 ↗
  • 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. PubMed 31675266 ↗
  • 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. PubMed 31654272 ↗
  • 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. PubMed 31144568 ↗
  • 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. PubMed 28835401 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00930553
Lead sponsor
Genzyme, a Sanofi Company
Collaborators
Bayer
Responsible party
Sponsor
First posted
Jun 30, 2009
Start date
Aug 2009
Primary completion
Feb 2016
Completion
Feb 2016
Results posted
May 15, 2017
Last update
May 15, 2017

Study contacts

Medical Monitor
study director · Genzyme Coorporation

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Alemtuzumab

Other studies in this condition

Multiple Sclerosis, Relapsing-Remitting →

Other studies from this sponsor

Genzyme, a Sanofi Company →

Start the discussion