The CARE-MSSM II Trial (comparison of alemtuzumab and rebif® Efficacy in multiple sclerosis): updated design of a phase 3, open-label, rater-blinded study of alemtuzumab in patients with multiple sclerosis who have relapsed on therapy

OBJECTIVE: Present current design for CARE-MS II. BACKGROUND: Alemtuzumab, a monoclonal antibody targeting CD52 antigen on lymphocytes, demonstrated superior efficacy and manageable safety profile in CAMMS223, a randomized, open-label, rater-blinded, phase 2 study of treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS). Three-year results from CAMMS223 showed that alemtuzumab reduced the rate of sustained accumulation of disability by 71% and the annualized relapse rate by 74% compared with interferon b-1a (IFNB-1a; both p<0.001). Moreover, mean expanded disability status scale (EDSS) scores improved by 0.39 point (approximately 22%) with alemtuzumab and worsened by 0.38 (approximately 13%) with IFNB-1a (p<0.001). Principal adverse events associated with alemtuzumab included infusion associated reactions, mild to moderate infection, and autoimmunity. Two phase 3 studies are currently ongoing: CARE-MS I trial to confirm alemtuzumab’s efficacy in treatment-naive MS, and CARE-MS II trial, presented here, to extend these findings to patients with active RRMS who have relapsed during prior treatment with a disease modifying therapy (DMT). DESIGN/METHODS: CARE-MS II, a phase 3, multinational, comparator-controlled study is enrolling patients aged 18–55 with a diagnosis of RRMS, ≥2 relapses in the past 24 months, an EDSS score ≤5.0, and symptom onset within the past 10 years. Patients must also have had ≥1 relapse on an interferon b or glatiramer acetate, after receiving the therapy for ≥6 months. Eligible patients are randomized 2:1 to 12 mg intravenous alemtuzumab (2 brief annual cycles) or 44 µg subcutaneous IFNB-1a 3 times/week for 2 years. The EDSS, multiple sclerosis functional composite, relapse, and MRI evaluations are performed by blinded raters. Suspected relapses are adjudicated by a blinded panel of MS experts. Patients also participate in the CARE-MS Safety Monitoring Program to optimize patient care. RESULTS: Enrollment will continue until approximately 573 patients are randomized to 12 mg alemtuzumab or IFNB-1a. CONCLUSIONS: The rater-blinded CARE-MS II trial is designed to establish efficacy and safety of alemtuzumab in patients with RRMS who relapsed during prior treatment with a DMT. Based on the superior efficacy and manageable safety profile of alemtuzumab in CAMMS223, after 2 years on study, alemtuzumab and IFNB-1a patients may be eligible to receive alemtuzumab re/treatment as part of an extension study.