Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05101AM3)(COMPLETED)
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Boceprevir (SCH 503034); Pegylated interferon alfa-2b (SCH 54031); Ribavirin (SCH 18908); Boceprevir placebo
Intervention description: Boceprevir, 200 mg capsules, 800 mg TID PO; PEG2b 1.5 μg/kg/week subcutaneously (SC); Ribavirin WBD 600 mg/day to 1400 mg/day by mouth (PO) divided twice daily (BID).; Boceprevir placebo, 200 mg capsules, 800 mg three times daily (TID) PO.
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 404.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treatment failure

Summary:

      This study involves treatment with boceprevir or placebo in combination with pegylated
      interferon alfa-2b (PegIntron, PEG2b) + Ribavirin (RBV) (weight-based dosing [WBD]) in adult
      subjects with chronic hepatitis C (CHC) genotype 1 who demonstrated interferon responsiveness
      (a decrease in hepatitis C virus RNA [HCV-RNA] viral load >=2 log10 by Week 12 or
      undetectable HCV-RNA at end of treatment) but who failed to achieve sustained virologic
      response (SVR) on prior treatment with any combination therapy of peginterferon alpha and
      RBV. This trial includes three arms, one control arm (PEG2b + RBV for 48 weeks) and two
      experimental arms (PEG2b + RBV + boceprevir). One of the experimental arms, Arm 3, consists
      of treatment with all three drugs for 44 weeks after the lead-in. The other experimental arm,
      Arm 2, consists of all three drugs for 32 weeks after the lead-in. Participants in Arm 2 who
      were undetectable for HCV-RNA at Treatment Week 8 will complete treatment at that point.
      Those who were not undetectable for HCV-RNA at Treatment Week 8 will receive an additional 12
      weeks of PEG2b + RBV + boceprevir placebo. It is hypothesized that the addition of a third
      active anti-HCV drug may lead to more rapid viral response than therapy with two drugs, and
      therefore, the addition of boceprevir to PEG2b plus RBV therapy after a 4-week lead-in period
      may allow for both increased rates of SVR and shorter treatment durations (in some
      populations) than treatment with peginterferon plus RBV alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Qualifying regimen defined as pegylated interferon alfa-2a plus ribavirin or pegylated
             interferon alfa-2b plus ribavirin for a minimum of 12 weeks.

          -  During qualifying regimen, participants must have either a documented undetectable
             HCV-RNA within 30 days of end of treatment (EOT) and a subsequent detectable HCV-RNA
             during follow-up or a documented decline in HCV-RNA by >=2 log10 by Treatment Week 12

          -  Previously documented CHC genotype 1 infection.

          -  Liver biopsy with histology consistent with CHC and no other etiology.

          -  Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6
             months of the Screening Visit (or between Screening and Day 1) with no findings
             suspicious for hepatocellular carcinoma (HCC).

          -  Participants participating in Schering-Plough Research Institute (SPRI) maintenance
             protocols P02570 (NCT00049842) or P02569 (NCT00048724) must have completed the study
             to be eligible for this protocol.

          -  Participants must be >=18 years of age.

          -  Participants must weigh between 40 kg and 125 kg.

          -  Participants and participant's partner(s) must each agree to use acceptable methods of
             contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months
             after last dose of study drug, or longer if dictated by local regulations.

          -  Participants must be willing to give written informed consent.

        Exclusion Criteria:

          -  Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus
             (Hepatitis B Surface Antigen [HBsAg] positive).

          -  Discontinuation of previous interferon or ribavirin regimen for an adverse event (AE)
             considered by the investigator to be possibly or probably related to ribavirin and/or
             interferon.

          -  Treatment with ribavirin within 90 days and any interferon-alpha within 1 month of
             Screening.

          -  Treatment for hepatitis C with any investigational medication. Prior treatment with
             herbal remedies with known hepatotoxicity.

          -  Treatment with any investigational drug within 30 days of the randomization visit.

          -  Participation in any other clinical trial within 30 days of randomization or intention
             to participate in another clinical trial.

          -  Evidence of decompensated liver disease including, but not limited to, a history or
             presence of clinical ascites, bleeding varices, or hepatic encephalopathy.

          -  Diabetic and/or hypertensive participants with clinically significant ocular
             examination findings.

          -  Pre-existing psychiatric conditions.

          -  Clinical diagnosis of substance abuse of the specified drugs within the specified
             timeframes

          -  Any known pre-existing medical condition that could interfere with the participant's
             participation in and completion of the study.

          -  Evidence of active or suspected malignancy, or a history of malignancy, within the
             last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of
             the skin). Participants under evaluation for malignancy are not eligible.

          -  Participants who are pregnant or nursing. Participants who intend to become pregnant
             during the study period. Male participants with partners who are, or intend to become,
             pregnant during the study period.

          -  Any other condition which, in the opinion of a physician, would make the participant
             unsuitable for enrollment or could interfere with the participant participating in and
             completing the study.

          -  Participants who are part of the site personnel directly involved with this study.

          -  Participants who are family members of the investigational study staff.

          -  Participants who had life-threatening serious adverse event (SAE) during screening
             period.

          -  Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin <12
             g/dL for females and <13 g/dL for males; Neutrophils <1500/mm^3 (Blacks: <1200/mm^3);
             Platelets <100,000/mm^3; Direct bilirubin >1.5 x upper limit of normal (ULN).

          -  Serum albumin <lower limit of normal (LLN)

          -  Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory reference
             range, with certain exceptions.

          -  Serum creatinine >ULN of the laboratory reference.

          -  Protocol-specified serum glucose concentrations.

          -  Protocol-specified alpha fetoprotein range.

          -  Prothrombin Time/Partial Thromboplastin Time (PT/PTT) values >10% above laboratory
             reference range.

          -  Anti-nuclear antibodies (ANA) >1:320.