Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05685AM2)(COMPLETED)
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Boceprevir; Placebo; Peginterferon alfa-2a; Ribavirin
Intervention description: 800 mg, using SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks; 800 mg, using placebo matching SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks; Peginterferon alfa-2a, pre-filled syringes, given 180 μg/week subcutaneously (SC) for 48 weeks; Ribavirin 200-mg capsules, weight-based dosing
<75 kg, 1000 mg/day orally (PO), divided twice daily (BID)
>=75 kg, 1200 mg/day PO, divided BID
for 48 weeks
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Based on previous experience with peginterferon alfa-2b/ribavirin in combination with
      boceprevir, the combination with peginterferon alfa-

      2a/ribavirin and boceprevir is expected to be safe and well tolerated. Given the wide
      utilization of both peginterferons and the clear benefit of the

      addition of boceprevir to peginterferon alfa-2b/ribavirin, it is important to demonstrate the
      safety and efficacy of boceprevir in combination with

      peginterferon alfa-2a/ribavirin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or
             peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.

          -  During the qualifying regimen, subjects must have either:

               -  A documented undetectable Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) within 30
                  days of the end-of-treatment and a subsequent detectable HCV-RNA during follow-up
                  OR

               -  A documented decline in HCV-RNA by >=2 log10 after 12 weeks of treatment.

          -  Subject must have previously documented chronic hepatitis C genotype 1 infection.

          -  Subject must have a liver biopsy with histology consistent with chronic hepatitis C
             infection and no other etiology.

          -  Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months
             with no findings suspicious for hepatocellular carcinoma (HCC).

          -  Subject must be >=18 years of age.

          -  Subject must weigh between 40 kg and 125 kg.

          -  Subject and subject's partner(s) must each agree to use acceptable methods of
             contraception.

          -  Subjects must be willing to give written informed consent.

        Exclusion Criteria:

        Subject will be excluded from entry if ANY of the criteria listed below are

        met:

          -  Subjects known to be coinfected with the human immunodeficiency virus (HIV) or
             hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) and/or demonstrating
             signs and symptoms consistent with co-infection.

          -  Subjects who required discontinuation of previous interferon or ribavirin regimen for
             an adverse event considered by the investigator to be possibly or probably related to
             ribavirin and/or interferon.

          -  Treatment with ribavirin within 90 days and any interferon alfa within 1 month of
             Screening.

          -  Treatment for hepatitis C with any investigational medication. Prior treatment with
             herbal remedies with known hepatotoxicity is exclusionary.

          -  Treatment with any investigational drug within 30 days of the randomization visit in
             this study.

          -  Participation in any other clinical trial within 30 days of randomization or intention
             to participate in another clinical trial during participation in this study.

          -  Evidence of decompensated liver disease.

          -  Diabetic and/or hypertensive subjects with clinically significant ocular examination
             findings.

          -  Pre-existing psychiatric condition(s).

          -  Clinical diagnosis of substance abuse.

          -  Any known pre-existing medical condition that could interfere with the subject'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).

          -  Subjects who are pregnant or nursing. Subjects who intend to become pregnant during
             the study period. Male subjects with partners who are or who intend to become pregnant
             during the study period.

          -  Any other condition which, in the opinion of a physician, would make the subject
             unsuitable for enrollment or could interfere with the subject participating in and
             completing the study.

          -  Subjects who are part of the site personnel directly involved with this study.

          -  Subjects who are family members of the investigational study staff.

          -  Subjects who had a life-threatening serious adverse event (SAE) during the screening
             period.

          -  Subjects with a history of pancreatitis, except for one episode clearly secondary to
             gallstone.

        Laboratory Exclusion Criteria:

          -  Hematologic, biochemical, and serologic criteria (growth factors may not be used to
             achieve study entry requirements):

               -  Hemoglobin (Hgb) <12 g/dL for females and <13 g/dL for males

               -  Neutrophils <1500/mm3 (blacks: <1200/mm3)

               -  Platelets <100,000/mm3

               -  Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference
                  range. Total bilirubin >1.6 mg/dL unless the subject has a history of Gilbert's
                  disease. If Gilbert's disease is the proposed etiology, this must be documented
                  in the subject's chart.

          -  Serum albumin < lower limit of normal (LLN) of laboratory reference range.

          -  Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory reference
             range.

          -  Serum creatinine >ULN of the laboratory reference range.

          -  Serum glucose:

               -  For subjects not previously diagnosed with diabetes mellitus:

                    -  >=140 mg/dL (nonfasting) unless hemoglobin A1c subtype (HbA1c) <=7% OR

                    -  >=100 mg/dL (fasting) unless HbA1c <=7%.

               -  For subjects previously diagnosed with diabetes mellitus: HbA1c >8.5%.

          -  Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory
             reference range.

          -  Anti-nuclear antibodies (ANA) >1:320.

          -  Alpha fetoprotein (AFP):

               -  AFP >100 ng/mL OR

               -  AFP 50 to 100 ng/mL requires a liver ultrasound and subjects with findings
                  suspicious for HCC are excluded.