Safety and Efficacy Study of Daclizumab High Yield Process to Treat Relapsing-Remitting Multiple Sclerosis (SELECT)

• the total lesion volume of new and newly enlarging T2 hyperintense lesions).
• brain MRI measures (total number of gadolinium-enhancing lesions, number of new or newly-enlarging T2 hyperintense lesions, volume of new T1 hypointense lesions, and

• Brain MRI measures (number of gd-enhancing lesions) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
• Proportion of relapsing subjects [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Improving quality of life as measured by Multiple Sclerosis Impact Scale (MSIS)-29 physical score [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Brain MRI measures (number of new or newly-enlarging T2 hyperintense lesions) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

• annualized relapse rate
• time to first relapse
• incidence of adverse events
• incidence of development of antibodies to daclizumab

The purpose of this study is to determine the effect of 2 different doses of daclizumab on reducing relapses in subjects with relapsing-remitting MS.

Primary Objective:

The primary objective of this study is to determine whether Daclizumab High Yield Process, when compared to placebo, is effective in reducing the rate of relapses between baseline and Week 52.

Secondary Objectives:

The secondary objectives are to determine whether Daclizumab High Yield Process is effective in:

• reducing the number of new Gd-enhancing lesions over 5 brain MRI scans at Weeks 8, 12, 16, 20, and 24 (calculated as the sum of these 5 MRIs) in a subset of subjects.
• reducing the number of new or newly-enlarging T2 hyperintense lesions at Week 52,
• reducing the proportion of relapsing subjects between baseline and Week 52,
• improving quality of life as measured by the Multiple Sclerosis Impact Scale (MSIS)-29 physical score at Week 52 compared to baseline.

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 400,000 persons in North America and 365,000 persons in Europe. Daclizumab High Yield Process (DAC HYP) is being co-developed by Biogen Idec Inc. (Biogen Idec) and AbbVie for treatment of MS. Daclizumab (DAC) produced using the AbbVie high-yield process is being investigated as an alternative. This study will determine if DAC HYP is safe and efficacious in subjects with relapsing-remitting multiple sclerosis (MS). A dose exploration placebo controlled study will be performed. Proof of profile will be sought that targeting of the alpha chain of the interleukin-2 receptor (IL-2Ralpha) without concomitant interferon (IFN) is effective in subjects with relapsing-remitting MS.

• Biological: Daclizumab High Yield Process
  150 mg (Subcutaneous) every 4 weeks for 48 weeks
• Other: placebo
  Subcutaneous
• Biological: Daclizumab High Yield Process
  300 mg (Subcutaneous) every 4 weeks for 48 weeks

• Placebo Comparator: 1
  subcutaneous (SC)
  Intervention: Other: placebo
• Experimental: 2
  Daclizumab High Yield Proces (Subcutaneous)
  Intervention: Biological: Daclizumab High Yield Process
• Experimental: 3
  Daclizumab High Yield Proces (Subcutaneous)
  Intervention: Biological: Daclizumab High Yield Process

Inclusion Criteria:

• MS subjects who have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 and a baseline EDSS (Expanded Disability Status Scale) between 0.0 and 5.0, inclusive, who meet either of the following 2 criteria

  • Have experienced at least 1 relapse within the 12 months prior to randomization, with a cranial MRI demonstrating lesion(s) consistent with MS , OR
  • Show evidence of gadolinium-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to randomization.

Exclusion Criteria:

• Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
• History of malignancy
• History of severe allergic or anaphylactic reactions or known drug hypersensitivity
• History of abnormal laboratory results
• History of human immunodeficiency virus (HIV) or other immunodeficient conditions
• History of drug or alcohol abuse ithin the 2 years prior to randomization
• An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization
• Positive screening for active infection with Hepatitis B virus or Hepatitis C virus
• Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening
• Exposure to varicella zoster virus within 21 days before Screening.
• Abnormal blood tests at Screening; Hemoglobin ≤9.0 g/dL, Platelets ≤100 × 109/L, Lymphocytes ≤1.0 × 109/L, Neutrophils ≤1.5 × 109/L, alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase >2 times the upper limit of normal (ULN) and serum creatinine >ULN.