Study of the Safety and Efficacy of MLN1202 in Patients in Multiple Sclerosis

A Phase 2a Magnetic Resonance Imaging Study of the Safety and Efficacy of MLN1202 in Patients in Multiple Sclerosis

This was a phase 2a study of MLN1202 to determine safety, tolerability and initial efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). It was conducted in 2 dose cohorts enrolling a total of 50 patients. Efficacy was assessed by comparing the numbers of new gadolinium-enhancing brain lesions during the screening and treatment periods.

Inclusion Criteria:

Each patient was to have met all of the following inclusion criteria to be enrolled in the study:

• 18 years of age or older
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
• An Expanded Disability Status Score (EDCC) of 0 to 5.5, inclusive
• Be willing and able to comply with the protocol for the duration of the study period
• Be willing to use adequate "double-barrier" contraceptive methods for the duration of the study period
• If female, must be neither pregnant or breast-feeding
• Written informed consent
• To be enrolled in the treatment phase of the study each patient must have a total of at least 2 new gadolinium-diethylenetriamine pentaacetic acid (Gd)-enhancing lesions seen over the series of 3 pretreatment magnetic resonance imaging (MRI)s.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria were not to be enrolled in the study:

• Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS)

• Received any investigational drug or experimental procedure within 3 months prior to study day 0

• If the patient has received disease-modifying treatments they must be discontinued prior to study day 0 as follows:

  1. Cyclophosphamide or mitoxantrone- 6 months prior
  2. Interferons, glatiramer acetate and azathioprine- 12 weeks prior
  3. Methotrexate, IV immunoglobulin, cyclosporin, plasma exchange or corticosteroids- 8 weeks prior

• Never have been exposed to Tysabri® (natalizumab)or any other VLA-4 (α4β1)antagonist

• Have an active infection or be considered to be at high risk for developing an infection

• Have a history of hepatitis B, C or human immunodeficiency virus (HIV)

• Have a chest X-ray within 6 months of study day 0 with clinically significant findings or abnormalities

• Have inadequate renal or hepatic function

• Have a known history of cancer, except for distant history (>10 years) of carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin

• Received any live, attenuated vaccinations within 30 days prior to study day 0

• Have a history of illicit drug or alcohol abuse within 5 years of study day 0

• Have a history of hypersensitivity to prior monoclonal antibody (mAb) treatment

• Have a history of allergy or sensitivity to Gd

• Have a history that would preclude serial MRI scans