A Study of TMC435350 Administered With or Without Standard of Care Therapy in Participants With Genotype 1 Hepatitis C Virus Infection
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to investigate how efficient TMC435350 will work against the
      Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and
      what the concentrations of TMC435350 in the blood are with or without pegylated interferon
      alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.
    

Detailed description: 
      This is a blinded (participant and study staff will not know the identity of assigned
      treatments), randomized (participants assigned to treatment by chance), placebo-controlled (a
      term used to describe a method of research in which an inactive substance referred to as a
      placebo is given to one group of participants, while the treatment being tested is given to
      another group) study to assess the effectiveness, safety, tolerability, and pharmacokinetics
      (to test the concentration of study drug in the blood over time) of different dose regimens
      of TMC435350 (hereafter referred to as TMC435) given alone or in combination with
      peginterferon alpha-2a (PegIFNa-2a) and ribavirin. TMC435 is a new drug that is development
      for the treatment of Hepatitis C virus (HCV) infection and belongs to a class of drugs that
      work by blocking an enzyme (protease) that the HCV needs to replicate. The combination of
      PegIFNa-2a and ribavirin are current standard of care (SoC) therapy for patients with chronic
      HCV infection. Approximately 72 participants with HCV infection who have never been treated
      for HCV infection (referred to as treatment-naïve participants) and 36 participants who have
      been treated for HCV infection (referred to as treatment-experienced participants) who did
      not respond to previous therapy with interferon (IFN) and who did not discontinue previous
      anti-HCV therapy because of adverse events [AEs]) will be included in this study. Two blinded
      placebo-controlled groups (referred to as "cohorts") of treatment-naïve participants will be
      sequentially initiated TMC435 to ensure that a higher dose is only administered if the
      previous lower dose is found safe and tolerable. The first group (Cohort 1) of
      treatment-naïve participants will receive low-doses of TMC435 or placebo for 7 days followed
      by 21 days of combined tritherapy with PegIFNa-2a and ribavirin OR participants will receive
      28 days of tritherapy (TMC435 or placebo + PegIFNa-2a and ribavirin). After review of data
      from Cohort 1, a second group (Cohort 2) of treatment-naïve participants will be given higher
      doses of TMC435 or placebo in the same manner described for the first cohort. A third group
      (Cohort 3) of participants previously planned in the study will not be enrolled. After review
      of data from Cohort 2, a fourth group (Cohort 4) of treatment-experienced participants will
      be given 28 days of TMC435 (or placebo) as tritherapy with PegIFNa-2a and ribavirin to
      determine the maximum tolerated dose of TMC435. In addition, up to 10 HCV-infected
      individuals (who participated in study TMC435350-TiDP16-C101 (ClinicalTrials.gov registry
      number NCT00938899) will comprise Cohort 5 and will be given 28 days of TMC435 at a dose
      previously determined to be safe and efficacious as tritherapy with PegIFNa-2a and ribavirin.
      Blood samples will be taken from participants at protocol-specified time points to determine
      plasma concentrations of TMC435 and ribavirin and safety will be monitored throughout the
      study. Individuals will participate in this study for up 54 weeks (includes up to 6 weeks
      during the screening period followed by up to 4 weeks of study treatment with TMC435 (or
      placebo) and up to a maximum of 44 weeks of treatment with PegIFNa-2a and ribavirin.
    

Intervention name(s): TMC435; Placebo; Peginterferon (PegIFNα-2a); Ribavirin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.; Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.; One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22; 200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.
Other intervention name(s): PEGASYS; COPEGUS
Intervention MeSH terms: Ribavirin; Simeprevir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Hepatitis C, Chronic; Tibotec; TMC435350-TiDP16-C201; TMC435350-C201; TMC435; PEGASYS (peginterferon alpha-2a, PegIFNα-2a); COPEGUS (ribavirin)