May 16, 2008
MS Trial Alert: Investigators Recruiting Participants with MS for Two Studies of Alemtuzumab
Investigators worldwide are recruiting subjects for two studies of alemtuzumab (Genzyme Corporation) for the treatment of relapsing-remitting MS. In the CARE-MSSM I study, approximately 525 subjects at over 100 study sites will be randomly assigned to receive alemtuzumab or Rebif® (interferon beta 1a, EMD Serono Inc. and Pfizer). In the CARE-MSSM II study, approximately 1200 subjects at over 250 study sites will be randomly assigned to receive one of two alemtuzumab treatment regimens, or Rebif. These studies are funded by Genzyme Corporation and Bayer Healthcare Pharmaceuticals.
Rationale: Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. Food and Drug Administration as a single agent for treatment of patients with B-cell chronic lymphocytic leukemia. Its ability to target immune cells has led investigators to test its potential as a treatment for relapsing-remitting MS.
At the Annual Meeting of the American Academy of Neurology in 2007, Dr. Alasdair J. Coles (Addenbrooke’s Hospital, University of Cambridge, UK) reported 2-year follow-up data from a Genzyme-sponsored Phase 2 clinical trial (CAMMS223, a study that is ongoing but not recruiting patients) comparing two dose levels of alemtuzumab with Rebif in subjects with relapsing-remitting MS who had never taken any other disease-modifying therapies. Those taking alemtuzumab experienced significant reductions in the risk of MS relapse compared with those taking Rebif (87% reduction in people taking the higher-dose alemtuzumab and 72% reduction in people taking the lower-dose alemtuzumab) as well as significant reductions in the risk for progression of disability compared with those taking Rebif (66% reduction in people taking higher-dose alemtuzumab and 88% reduction in people taking lower-dose alemtuzumab).
Dosing in the Phase 2 study was temporarily suspended due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first case of ITP, which was a fatal case, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients. Five additional alemtuzumab-associated ITP cases were identified and, when necessary, promptly treated; currently these patients are in remission, off ITP treatment. The CARE-MSSM I and CARE-MSSM II studies include the same patient monitoring program for all patients, including monthly (or more frequent) blood tests and monthly surveys to monitor for the signs and symptoms of ITP.
Among other side effects reported in the Phase 2 study, patients who received alemtuzumab were more likely to develop thyroid disease and mild to moderate infections (i.e., infections requiring no specific medical intervention or requiring only oral medication). Thyroid problems are reported to have been easily detected and treated. Patients who received Rebif experienced injection site reactions, fatigue, flu-like illness, headache and abnormal liver function tests.
Eligibility and Details: To enroll in either the CARE-MSSM I or CARE-MSSM II study, participants who have been diagnosed with relapsing-remitting MS should be between the ages of 18 and 50.
In the CARE-MSSM I study, approximately 350 participants will receive alemtuzumab (administered intravenously in two annual cycles, once a day for 5 consecutive days at the beginning of the study and once a day for 3 consecutive days 1 year later) and approximately 175 subjects will receive Rebif (44 mcg administered three times weekly under the skin) for two years. This study will enroll subjects who have not previously received disease-modifying treatment for multiple sclerosis, except steroids.
In the CARE-MSSM II study, approximately 480 participants will receive 12 mg/day alemtuzumab and approximately 480 participants will receive 24 mg/day alemtuzumab (both alemtuzumab doses are administered intravenously in two annual cycles, once a day for 5 consecutive days at the beginning of the study and once a day for 3 consecutive days 1 year later). Additionally, approximately 240 people will receive Rebif (44 mcg administered three times weekly under the skin) for two years. This study will enroll subjects who have received an adequate trial of disease-modifying therapies but continued to relapse (at least once) while being treated, and who meet a minimum severity of disease as measured by MRI.
The primary goals of both studies are to establish the efficacy (in reducing accumulation of disability and relapse rate) and safety of alemtuzumab, as a treatment for relapsing-remitting MS, in comparison with Rebif.
Contact: For further information about enrolling in either of these studies, please contact:
Genzyme Medical Information at (800) 745-4447 (toll free in the United States only) or medinfo@genzyme.com.
CARE-MSSM is a servicemark of Genzyme Corporation
Rebif® is a registered trademark of EMD Serono Inc.