CAMMS323: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study One (CARE-MS SM I)

CAMMS323: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study One (CARE-MS ^SM I)

Sponsored By:	Genzyme
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00530348

The purpose of this study is to establish the efficacy and safety of alemtuzumab as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with Rebif® (interferon beta-1a). The study will enroll patients who have not previously received treatment to suppress MS, except steroids. Patients will have monthly blood tests and comprehensive testing every 3 months.

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Drug: alemtuzumab (Campath® / MabCampath®) Drug: interferon beta-1a (Rebif®)	Phase 3

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis.

Primary Outcome Measures:
Time to Sustained Accumulation of Disability (SAD) [Time Frame: 2 years]
Relapse Rate [Time Frame: 2 years]

Secondary Outcome Measures:
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]

Every patient will receive active treatment; there is no placebo. Patients who qualify will be randomly assigned to treatment with either alemtuzumab or Rebif® at a 2:1 ratio (ie, 2 given alemtuzumab for every 1 given Rebif®). Alemtuzumab will be administered in two annual cycles, once at the beginning of the study and again 1 year later. Rebif® will be self-injected 3 times per week for as long as the study continues. All patients will be required to return to their study site every 3 months for neurologic assessment. In addition, a safety-related blood test will be performed at least monthly. Participation in this study is estimated to last between 2 and 4 years; patients who receive alemtuzumab will be followed for at least 3 years after their last dose of alemtuzumab.

Diagnosis of MS and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years of screening

Onset of MS symptoms within 5 years of screening

EDSS score 0.0 to 3.0

≥2 MS attacks occurring in the 24 months prior to screening, with ≥1 attack in the 12 months prior to screening

Received prior therapy for MS other than corticosteroids

Exposure to immunosuppressive or immunomodulatory agents other than systemic corticosteroid treatment

Received treatment with a monoclonal antibody for any reason

Has any progressive form of MS

Any disability acquired from trauma or another illness that could interfere with evaluation of disability due to MS

Major systemic disease that cannot be treated or adequately controlled by therapy

Chronic infection with viral, mycobacterial or parasitic organisms

Autoimmune disorder (other than MS)

Impaired hepatic or renal function

History of malignancy (exception for basal cell skin carcinoma if disease-free for ≥5 years)

Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study

Of childbearing potential with a positive serum pregnancy test

Current participation in another clinical study

Previous hypersensitivity reaction to other immunoglobulin product

Known allergy or intolerance to interferon beta, human albumin, or mannitol

Intolerance of pulsed corticosteroids, especially a history of steroid psychosis

Inability to self-administer subcutaneous (SC) injections or receive SC injections from caregiver

Inability to undergo MRI with gadolinium administration

Unwilling to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only)

United States, Arizona
Barrow Neurology Clinics at St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, United States; Recruiting

United States, Colorado
Advanced Neurosciences Research LLC, Fort Collins, Colorado, United States; Recruiting

United States, Florida
Axiom Clinical Research of Florida, Tampa, Florida, United States; Recruiting

United States, Illinois
Consultants in Neurology, Ltd., Northbrook, Illinois, United States; Recruiting

United States, Indiana
Fort Wayne Neurological Center, Fort Wayne, Indiana, United States; Recruiting

United States, Michigan
Michigan Medical, P.C., Neurology, Grand Rapids, Michigan, United States; Recruiting

United States, Ohio
The Ohio State University Medical Center, Columbus, Ohio, United States; Recruiting

United States, Tennessee
Sibyl Wray, MD, Neurology, PC Knoxville, Tennessee, United States; Recruiting

United States, Texas
Integra Clinical Research, L.L.C., San Antonio, Texas, United States; Recruiting
Central Texas Neurology Consultants, Round Rock, Texas, United States; Recruiting
Neurology Center of San Antonio, San Antonio, Texas, United States; Recruiting
Baylor College of Medicine, Houston, Texas, United States; Recruiting

United Kingdom
Addenbrooke's Hospital, Cambridge, United Kingdom; Recruiting

Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. Epub 2005 Jul 27. : 16044212

Study ID Numbers: CAMMS323
ClinicalTrials.gov Identifier: NCT00530348
Health Authority: United States: Food and Drug Administration; Canada: Health Canada; Australia: Department of Health and Ageing Therapeutic Goods Administration; Czech Republic: State Institute for Drug Control; Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Sweden: Medical Products Agency; United Kingdom: Medicines and Healthcare Products Regulatory Agency; France: Afssaps - French Health Products Safety Agency; Germany: Paul-Ehrlich-Institut; Croatia: Ministry of Health and Social Care; Serbia and Montenegro: Agency for Drugs and Medicinal Devices; Ukraine: State Pharmacological Center - Ministry of Health; Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica; Russia: Ministry of Health and Social Development of the Russian Federation; Mexico: Federal Commission for Sanitary Risks Protection (SSA); Brazil: National Health Surveillance Agency