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

October 22, 2007
January 6, 2015
October 2007
September 2011   (final data collection date for primary outcome measure)
  • Percentage of Participants With Sustained Accumulation of Disability (SAD) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    EDSS is an ordinal scale in half-point increments that qualifies 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: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with a Baseline score of 1.0 or more; and the increase persisted for at least the next 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Percentage of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
  • Annualized Relapse Rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated through negative binomial regression with robust variance estimation and covariate adjustment for geographic region using observed number of relapses as dependent variable, the log total amount of follow-up from date of first study treatment for each participant as an offset variable, and treatment group and geographic region as model covariates.
  • Time to Sustained Accumulation of Disability (SAD) [ Time Frame: 2 years ]
  • Relapse Rate [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00548405 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Who Were Relapse Free at Year 2 [ Time Frame: Year 2 ] [ Designated as safety issue: No ]
    Participants were considered relapse free at Year 2 if they did not experience a relapse from the date of first study treatment to study completion at 24 months. Percentage of participants who were relapse free at Year 2, estimated using the KM method, was reported.
  • Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    EDSS is an ordinal scale in half-point increments that qualifies 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). Change was calculated by subtracting Baseline value from value at Year 2.
  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    MSFC is a multidimensional measure consisting of quantitative tests of ambulation (Timed 25-Foot Walk), manual dexterity (9-Hole Peg Test; 9HPT), and cognitive function (Paced Auditory Serial Addition Test; PASAT). The MSFC score was calculated as the mean of the Z-scores of the 3 components. A Z-score was calculated by subtracting the mean of the reference population from the test result, then dividing by the standard deviation of the reference population. Higher Z-scores reflected better neurological function and a positive change from Baseline indicates improvement. An increase in score indicated an improvement (Z-score range: -3 to +3). Acquisition of disability was measured by change from Baseline in MSFC score at Year 2.
  • Percent Change From Baseline in Magnetic Resonance Imaging Time Constant 2 (MRI-T2) Hyperintense Lesion Volume at Year 2 [ Time Frame: Baseline, Year 2 ] [ Designated as safety issue: No ]
    Percent change in MS lesion volume as measured by MRI-T2 scan was calculated from MRI-T2-weighted scans as the following: (lesion volume at 2 years - lesion volume at Baseline)*100/ (lesion volume at Baseline).
  • Proportion of patients who are relapse free at Year 2 [ Time Frame: 2 years ]
  • Change from baseline in EDSS [ Time Frame: 2 years ]
  • Acquisition of disability as measured by change from baseline in MSFC [ Time Frame: 2 years ]
  • Percent change from baseline in MRI-T2 hyperintense lesion volume at Year 2 [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, Study Two
A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta 1a (Rebif®) in Patients With Relapsing Remitting Multiple Sclerosis Who Have Relapsed On Therapy

The purpose of this study was to establish the efficacy and safety of two different doses of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous interferon beta-1a (Rebif®). The study enrolled participants who had received an adequate trial of disease-modifying therapies but experienced at least 1 relapse during prior treatment, and who met a minimum severity of disease as measured by magnetic resonance imaging (MRI). Participants had monthly laboratory tests and comprehensive testing every 3 months.

Every participant received active treatment; there was no placebo. After Amendment 2, the 24 mg alemtuzumab dose was closed to enrollment so newly enrolled participants were randomly assigned to treatment with either 12 mg alemtuzumab or interferon beta-1a in a 2:1 ratio (that is, 2 given 12 mg alemtuzumab for every 1 given interferon beta-1a). Alemtuzumab was administered in two annual courses, once at the beginning of the study and again 1 year later. Interferon beta-1a was self-injected 3 times per week for 2 years. All participants were required to return to their study site every 3 months for neurologic assessment. In addition, safety-related laboratory tests were performed at least monthly. Participation in this study ended 2 years after the start of treatment for each participant. Additionally, participants who received alemtuzumab might be followed in the CAMMS03409 Extension Study (NCT00930553) for safety and efficacy assessments. Participants who received interferon beta-1a and completed 2 years on study might be eligible to receive alemtuzumab in the Extension Study.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Multiple Sclerosis, Relapsing-Remitting
  • Biological: Alemtuzumab 12 mg
    Alemtuzumab 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.
    Other Name: Lemtrada
  • Biological: Alemtuzumab 24 mg
    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.
    Other Name: Lemtrada
  • Biological: Interferon beta-1a
    Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.
    Other Name: Rebif®
  • Experimental: Alemtuzumab 12 mg
    Intervention: Biological: Alemtuzumab 12 mg
  • Experimental: Alemtuzumab 24 mg
    Intervention: Biological: Alemtuzumab 24 mg
  • Active Comparator: Interferon Beta-1a
    Intervention: Biological: Interferon beta-1a

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
840
September 2011
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Signed informed consent form (ICF)
  • Age 18 to 55 years (inclusive) as of the date the ICF was signed
  • Diagnosis of MS per update of McDonald criteria
  • Onset of MS symptoms (as determined by a neurologist; could be retrospectively) within 10 years of the date the ICF was signed
  • Expanded Disability Status Scale (EDSS) score 0.0 to 5.0 (inclusive) at Screening
  • Greater than or equal to (>=) 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF was signed, with >=1 attack in the 12 months prior to the date the ICF was signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider and the objective signs could be identified retrospectively
  • >=1 MS relapse during treatment with a beta interferon therapy or glatiramer acetate after having been on that therapy for >=6 months within 10 years of the date the ICF was signed
  • MRI scan demonstrating white matter lesions attributable to MS and meeting at least 1 of the following criteria, as determined by the neurologist or a radiologist: >=9 time constant 2 (T2) lesions at least 3 millimeter (mm) in any axis; a gadolinium- (Gd-) enhancing lesion at least 3 mm in any axis plus >=1 brain T2 lesions; and a spinal cord lesion consistent with MS plus >=1 brain T2 lesion

Exclusion Criteria:

  • Received prior therapy with alemtuzumab
  • Current participation in another clinical study or previous participation in CAMMS323 (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, CARE-MS I)
  • Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6 months. Participants who received one of these medications more than 6 months before the date the ICF was signed were eligible for study entry if approval was granted by Genzyme
  • Any progressive form of MS
  • History of malignancy (except basal skin cell carcinoma)
  • CD4 +, CD8 +, CD19 + (that is, absolute CD3 + CD4 + , CD3 + CD8 + , or CD19 + /mm 3 ) count, absolute neutrophil count less than (<) lower limit of normal (LLN) at screening; if abnormal cell count(s) returned to within normal limits (WNL), eligibility could be reassessed
  • Known bleeding disorder (for example, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen deficiency, or clotting factor deficiency)
  • Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis
  • Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (that is, above the LLN)
  • Active infection or at high risk for infection
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Croatia,   Czech Republic,   Denmark,   France,   Germany,   Israel,   Italy,   Mexico,   Netherlands,   Poland,   Russian Federation,   Serbia,   Spain,   Sweden,   Ukraine,   United Kingdom
 
NCT00548405
CAMMS32400507, 2007-001162-32, CAMMS324,, ISRCTN70702834, ACTRN12608000426381, NTR1469, CARE-MS II
Yes
Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Bayer
Study Director: Medical Monitor Genzyme, a Sanofi Company
Sanofi
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP