CARE-MS I STUDY

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

 

INCLUSION/EXCLUSION CRITERIA: 

Patients must meet all of the following criteria to be eligible for enrollment in this study:

 
1. Signed, informed consent form (ICF)
2. Age 18 to 50 years old (inclusive) as of signing informed consent form (ICF)
3. Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years of screening
4. Onset of MS symptoms (as determined by a neurologist) within 5 years of screening
5. EDSS score 0.0 to 3.0 (inclusive)
6. =2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with =1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician 

Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:

 
1. Received prior therapy for MS other than corticosteroids, eg, interferons, IV immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone
2. Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment
3. Received treatment with a monoclonal antibody for any reason
4. Has any progressive form of MS
5. History of malignancy (exception for basal cell skin carcinoma if disease-free for =5 years)
6. Any disability acquired from trauma or another illness that, in the opinion of the Investigator, could interfere with evaluation of disability due to MS
7. Previous hypersensitivity reaction to other immunoglobulin product
8. Known allergy or intolerance to interferon beta, human albumin, or mannitol
9. Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
10. Inability to self-administer SC injections or receive SC injections from caregiver
11. Inability to undergo MRI with gadolinium administration
12. Documented CD4+ cell count <490/mm3 within the past year
13. Documented CD8+ cell count <200/mm3 within the past year
14. Seropositivity for human immunodeficiency virus (HIV)
15. Significant autoimmune disease (eg, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis)
16. Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies
17. Active infection, eg, deep-tissue infection, that the Investigator considers sufficiently serious to preclude study participation
18. Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis. More specific guidance on tuberculosis testing and patient eligibility is provided in the Study Operations Manual (SOM)
19. Infection with hepatitis B virus or hepatitis C virus
20. Of childbearing potential with a positive serum pregnancy test
21. Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only); reliable and effective contraceptive method(s) include: condoms (male or female) with or without a spermicidal agent, diaphragm with spermicide or cervical cap, intrauterine device (IUD), or hormonal-based contraception
22. Major psychiatric disorder that is not adequately controlled by treatment
23. Epileptic seizures that are not adequately controlled by treatment
24. Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results
25. Current participation in another clinical study
26. Medical, psychiatric, cognitive, or other conditions that, in the Investigator’s opinion, 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
27. Confirmed platelet count < the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at <100,000/µL within the past year on a sample without clumping
28. Prior history of invasive fungal infections
29. History of untreated cervical dysplasia or intraepithelial neoplasia (CIN)
30. Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only). Guidance on region-specific testing recommendations and patient eligibility is provided in the SOM
31. Any other illness or infection (latent or active) that, in the Investigator’s opinion, could be exacerbated by alemtuzumab treatment
32. Any hepatic or renal function value grade 2 or higher at Screening with the exception of hyperbilirubinemia due to Gilbert’s syndrome. See Table below, drawn from the National Cancer

Hepatic
Bilirubin >1.5 × ULN
SGOT/AST >2.5 × ULN
SGPT/ALT >2.5 × ULN
Alkaline phosphatase >2.5 × ULN
Renal
Creatinine >1.5 × ULN