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

Genzyme

Status and phase: Completed; Phase 3

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Biological: Alemtuzumab 24 mg; Biological: Interferon beta-1a; Biological: Alemtuzumab 12 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00548405

NTR1469 (Registry Identifier)

CAMMS324,

CARE-MS II (Other Identifier)

2007-001162-32 (EudraCT Number)

ACTRN12608000426381 (Registry Identifier)

CAMMS32400507

ISRCTN70702834 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 840 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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840 participants in 3 patient groups

Alemtuzumab 12 mg

Experimental group

Description:

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.

Treatment:

Biological: Alemtuzumab 12 mg

Alemtuzumab 24 mg

Experimental group

Description:

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.

Treatment:

Biological: Alemtuzumab 24 mg

Interferon Beta-1a

Active Comparator group

Description:

Interferon Beta-1a (Rebif®) 44 microgram (mcg) subcutaneously 3-times weekly for 24 months. Dose adjustment was done as per Investigator's discretion.

Treatment:

Biological: Interferon beta-1a