CARE-MSII Study

 A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Patients with Relapsing-Remitting Multiple Sclerosis Who Have Relapsed On Therapy 

Protocol Number: CAMMS32400507

 

Inclusion Criteria: 

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

(1) Signed, informed consent form

(2) Age 18 to 50 years old (inclusive) as of signing informed consent form (ICF)

(3) Diagnosis of MS per update of McDonald criteria

(4) Onset of MS symptoms (as determined by a neurologist) within 5 years of screening

(5) EDSS score 0.0 to 5.0 (inclusive)

(6) ≥2 MS attacks (first episode or relapses) occurring in the 2 years prior to screening, with

≥1 attack in the 1 year prior to screening, with objective neurological signs confirmed by

a physician

(7) ≥6 months continuous treatment with beta interferon or glatiramer acetate during the past

5 years prior to screening.

(8) ≥1 MS attack (relapse) during treatment with interferon beta or glatiramer acetate after

being on that therapy for at least 6 months; relapses that occur within 6 months of

initiating treatment with interferon beta or glatiramer acetate do not qualify as a relapse

during treatment

(9) MRI scan demonstrating white matter lesions attributable to MS and meeting at least one

of the following criteria, as determined by the treating neurologist

o ≥9 T2 lesions at least 3 mm in any axis

o a gadolinium-enhancing lesion at least 3 mm in any axis plus ≥1 brain T2 lesions

o a spinal cord lesion consistent with MS plus ≥1 brain T2 lesions

 

Exclusion Criteria:

(1) Previous treatment with alemtuzumab or any other investigational drug for MS

(2) Previous treatment with mitoxantrone or natalizumab

(3) Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate,

or any other immunosuppressive agent other than systemic corticosteroid treatment

(4) Received treatment with a monoclonal antibody for any reason

(5) Has any progressive form of MS

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

(7) Any disability acquired from trauma or another illness that, in the opinion of the

Investigator, could interfere with evaluation of disability due to MS

(8) Previous hypersensitivity reaction to other immunoglobulin product

(9) Known allergy or intolerance to interferon beta, human albumin, or mannitol

(10) Intolerance of pulsed corticosteroids, especially a history of steroid psychosis

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

(12) Inability to undergo MRI with gadolinium administration

(13) Documented CD4+ cell count <490/mm3 within the past year

(14) Documented CD8+ cell count <200/mm3 within the past year

(15) Seropositivity for human immunodeficiency virus (HIV)

(16) Significant autoimmune disease (eg, immune cytopenias, rheumatoid arthritis, systemic

lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel

disease; severe psoriasis)

(17) Presence of anti-TSH receptor antibodies

(18) Active infection, eg, deep-tissue infection, that the Investigator considers sufficiently

serious to preclude study participation

(19) 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).

(20) Infection with hepatitis B virus or hepatitis C virus

(21) Of childbearing potential with a positive serum pregnancy test

(22) 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.

(23) Major psychiatric disorder that is not adequately controlled by treatment

(24) Epileptic seizures that are not adequately controlled by treatment

(25) 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

(26) Current participation in another clinical study or previous participation in CAMMS32

(27) 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

(28) Confirmed platelet count <130,000/μL at Screening or documented at <100,000/μL

within the past year on a sample without platelet clumping

(29) Prior history of invasive fungal infections

(30) History of untreated cervical dysplasia or intraepithelial neoplasia (CIN)

(31) 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.

(32) Any other illness or infection (latent or active) that, in the Investigator’s opinion, could

be exacerbated by alemtuzumab treatment

(33) Any hepatic or renal function value grade 2 or higher at screening (See Table below,

drawn from the National Cancer Institute (NCI) Common Terminology Criteria for

Adverse Events v3.0 (CTCAE), published 09 August 2006, with the exception of

hyperbilirubinemia due to Gilbert’s syndrome: