Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two (CARE-MS II)

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00548405
First received: October 22, 2007
Last updated: January 6, 2015
Last verified: January 2015
Results First Received: November 17, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Condition: Multiple Sclerosis, Relapsing-Remitting
Interventions: Biological: Alemtuzumab 12 mg
Biological: Alemtuzumab 24 mg
Biological: Interferon beta-1a

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were screened at 192 investigational sites between October 10, 2007 and September 15, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Interferon Beta-1a Interferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Alemtuzumab 12 mg Alemtuzumab (Lemtrada™) 12 milligram (mg) per day intravenous (IV) infusion on 5 consecutive days at Month 0, followed by alemtuzumab 12 mg per day IV infusion on 3 consecutive days at Month 12.
Alemtuzumab 24mg Alemtuzumab 24 mg per day IV infusion on 5 consecutive days at Month 0, followed by alemtuzumab 24 mg per day IV infusion on 3 consecutive days at Month 12.

Participant Flow:   Overall Study
    Interferon Beta-1a     Alemtuzumab 12 mg     Alemtuzumab 24mg  
STARTED     231 [1]   436 [1]   173 [1]
Treated     202 [2]   426 [2]   170 [2]
COMPLETED     175     416     164  
NOT COMPLETED     56     20     9  
Adverse Event                 6                 2                 0  
Lack of Efficacy                 6                 0                 0  
Physician Decision                 3                 4                 1  
Pregnancy                 1                 0                 0  
Protocol Violation                 1                 0                 0  
Withdrawal by Subject                 36                 12                 5  
Lost to Follow-up                 1                 1                 2  
Death                 0                 1                 1  
Sponsor decision                 1                 0                 0  
Randomized but not treated                 1                 0                 0  
[1] Randomized.
[2] All randomized participants who received at least 1 dose of study drug as per initial randomization.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) population included all randomized participants who received at least 1 dose of study drug as per initial randomization.

Reporting Groups
  Description
Interferon Beta-1a Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
Alemtuzumab 12 mg Alemtuzumab 12 mg per day IV infusion on 5 consecutive days at Month 0, followed by alemtuzumab 12 mg per day IV infusion over 4 hours on 3 consecutive days at Month 12.
Alemtuzumab 24mg Alemtuzumab 24 mg per day IV infusion on 5 consecutive days at Month 0, followed by alemtuzumab 24 mg per day IV infusion over 4 hours on 3 consecutive days at Month 12.
Total Total of all reporting groups

Baseline Measures
    Interferon Beta-1a     Alemtuzumab 12 mg     Alemtuzumab 24mg     Total  
Number of Participants  
[units: participants]
  202     426     170     798  
Age  
[units: years]
Mean ± Standard Deviation
  35.8  ± 8.77     34.8  ± 8.36     35.1  ± 8.40     35.1  ± 8.47  
Gender  
[units: participants]
       
Female     131     281     120     532  
Male     71     145     50     266  
Time Since First Relapse  
[units: years]
Median ( Full Range )
  4.1  
  ( 0.4 to 10.1 )  
  3.8  
  ( 0.2 to 14.4 )  
  3.7  
  ( 0.2 to 16.9 )  
  3.8  
  ( 0.2 to 16.9 )  
Number of Relapse Episodes in the Preceding 2 Years [1]
[units: participants]
       
1 Relapse     7     15     11     33  
2 Relapses     109     215     94     418  
Greater than or equal to 3 Relapses     86     196     65     347  
Expanded Disability Status Scale (EDSS) Score [2]
[units: units on a scale]
Mean ± Standard Deviation
  2.7  ± 1.21     2.7  ± 1.26     2.7  ± 1.17     2.7  ± 1.22  
[1] Number of participants with 1, 2 or greater than or equal to 3 relapses are reported.
[2] EDSS is an ordinal scale in half-point increments that quantifies disability in participants with multiple sclerosis (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).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Sustained Accumulation of Disability (SAD)   [ Time Frame: Up to 2 years ]

2.  Primary:   Annualized Relapse Rate   [ Time Frame: Up to 2 years ]

3.  Secondary:   Percentage of Participants Who Were Relapse Free at Year 2   [ Time Frame: Year 2 ]

4.  Secondary:   Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2   [ Time Frame: Baseline, Year 2 ]

5.  Secondary:   Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2   [ Time Frame: Baseline, Year 2 ]

6.  Secondary:   Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2   [ Time Frame: Baseline, Year 2 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Efficacy analysis was not performed for Alemtuzumab 24 mg as recruitment to this arm was closed early to reduce overall sample size, duration of enrollment period, overall duration of study.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-us@sanofi.com


Publications:
Publications automatically indexed to this study:

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00548405     History of Changes
Other Study ID Numbers: CAMMS32400507, 2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Study First Received: October 22, 2007
Results First Received: November 17, 2014
Last Updated: January 6, 2015
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Ministry for Health Family and Youth
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Medical Ethics Review Committee (METC)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency