An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
Condition: Relapsing-Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Midazolam; Caffeine; S-warfarin; Vitamin K; Omeprazole; Dextromethorphan; BIIB019 (Daclizumab)
Intervention description: 5 mg; 200 mg; 10 mg; 10 mg; 40 mg; 30 mg; 150 mg in 1 ml PFS
Intervention MeSH terms: Vitamin K; Midazolam; Dextromethorphan; Caffeine; Omeprazole; Warfarin; Daclizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 133.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Pre-filled syringe; Pharmacokinetic; Daclizumab High Yield Process; immunogenicity

Summary:

      The primary objective of the study is to assess the immunogenicity of Daclizumab High Yield
      Process (DAC HYP) 150 mg administered every 4 weeks by subcutaneous (SC) injection using the
      pre-filled syringe (PFS) in participants with relapsing-remitting multiple sclerosis (RRMS).
      The secondary objectives of this study are to characterize the pharmacokinetics (PK) of DAC
      HYP following single and multiple doses of DAC HYP administered by the PFS in a subset of
      participants with RRMS and to evaluate the effect of DAC HYP on the PK of probe drugs for
      cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous
             cranial magnetic resonance imaging demonstrating lesion(s) consistent with MS

          -  Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0,
             inclusive

          -  Must have had 1 or more clinical relapses within the previous 2 years

          -  Women of child bearing potential must be willing to practice effective contraception
             during the study and 4 months after the last dose

        Key Exclusion Criteria:

          -  Other chronic disease of the immune system, malignancies, acute urologic, pulmonary,
             gastrointestinal disease

          -  Female subjects who are currently pregnant or breastfeeding

        Key Inclusion criteria for 3-Year Treatment Extension:

        To be eligible for participation in the 3-year treatment extension, participants must meet
        the following eligibility criteria at the time of reinitiation of DAC HYP:

          -  Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial
             24-week treatment period and the 20-week washout period in the opinion of the
             Investigator

          -  Must resume DAC HYP treatment ≤12 weeks after completion of the washout period (i.e.,
             ≤12 weeks after their Week 44 visit).

          -  Participants who are currently receiving an approved IFN ß preparation must
             discontinue interferon (IFN) ß treatment at the time of reinitiation of DAC HYP dosing
             (no washout is required).

        Key Inclusion criteria for the TP-DI Sub-study:

        To be eligible for participation in the TP-DI Sub-Study, subjects must meet the following
        eligibility criteria at the Screening Visit at Week 40:

          -  Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial
             24-week treatment period and through Week 40 of the 20-week washout period in the
             opinion of the Investigator.

          -  Must agree to resume DAC HYP treatment ≤12 weeks after completion of the washout
             period (i.e., ≤12 weeks after their Week 44 visit).

          -  Must have normal liver function test results (total bilirubin ≤1.5 × upper limit of
             normal (ULN), alanine aminotransferase/aspartate aminotransferase ≤2 × ULN, and
             prothrombin time/partial thromboplastin time ≤1.2 × ULN).

          -  Must have normal renal function as estimated creatinine clearance >60 mL/min
             (Cockcroft-Gault formula).

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.