A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4)

• Number of Participants Achieving SVR Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control) [ Time Frame: 24 weeks after treatment (FW 24) ] [ Designated as safety issue: No ]
  SVR is defined as undetectable plasma HCV-RNA at FW 24. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
• Number of Participants With Early Virologic Response (EVR) Among Those Participants Who Achieved SVR [ Time Frame: Treatment Week (TW) 2 up to TW 12 ] [ Designated as safety issue: No ]
  EVR was defined as undetectable HCV-RNA at TW 2, 4, 8, or 12. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
• Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 [ Time Frame: 12 weeks after treatment (FW 12) ] [ Designated as safety issue: No ]
  HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
• Change from Baseline in log10 HCV-RNA at Treatment Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
• Number of Participants with HCV Virologic Breakthrough or Incomplete Virologic Response/rebound. [ Time Frame: 24 weeks after treatment (FW 24) ] [ Designated as safety issue: No ]
  Virologic Breakthrough defined as any participant who achieves undetectable HCV-RNA and subsequently has an HCV-RNA level of >1000 IU/mL. Incomplete Virologic Response/Rebound: a 1 log10 increase in HCV-RNA from the participant's nadir, with an HCV-RNA >1000 IU/mL. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.

The primary objective of this trial is to compare the efficacy of boceprevir (SCH 503034) 800 mg three times a day (TID) orally (PO) in combination with peginterferon alfa-2b (PEG2b) 1.5 ug/kg weekly (QW) subcutaneously (SC) plus weight-based dosing (WBD) of ribavirin (R) (600 mg/day to 1400 mg/day) PO to therapy with PEG2b + R alone in adult participants coinfected with human immunodeficiency virus (HIV) and previously untreated chronic hepatitis C virus (HCV) genotype 1.

Boceprevir is a potent, orally administered, novel serine protease inhibitor, specifically designed to inhibit the HCV nonstructural protein 3 (NS3) protease and, thereby, inhibit viral replication in HCV-infected host cells. The mechanism of inhibition represents a new mechanism of action compared to both interferon alfa and ribavirin. Based on previous experience with PEG2b and ribavirin in combination (PEG2b/R) with boceprevir in the HCV-monoinfected population, this combination treatment is expected to provide significant benefit to the HIV/HCV coinfected population. Given the high unmet medical need of these participants and the benefit of the addition of boceprevir to PEG2b/R, it is important to demonstrate the safety and efficacy of boceprevir in combination with PEG2b/R in participants coinfected with HIV/HCV.

This is a randomized, multi-center trial, double-blinded for boceprevir or placebo in combination with open-label PEG2b/R in participants coinfected with HIV and previously untreated chronic HCV (genotype 1), to be conducted in conformance with Good Clinical Practice (GCP). This trial consists of two arms, one control arm (Arm1) and one experimental arm (Arm 2). Participants in the control arm (Arm1) may receive boceprevir/PEG2b/R via a crossover arm.

• HIV Infections
• Hepatitis C
• HCV Infection

• Drug: PEG2b
  PEG2b (1.5 μg/kg/week SC) for 4 weeks
• Drug: Ribavirin
  Ribavirin (600-1400 mg/day divided BID PO) for 4 weeks
• Drug: Placebo to Boceprevir
  Placebo to boceprevir (800 mg TID PO) for 44 weeks
• Drug: Boceprevir
  Boceprevir (800 mg TID PO) for 44 weeks

• Placebo Comparator: Control Arm
  PEG2b (1.5 µg/kg/week SC) plus ribavirin (600-1400 mg/day divided BID PO) for 4 weeks followed by placebo plus PEG2b/R for 44 weeks with 24 weeks post-treatment follow-up (Control Arm)
  Interventions:

  • Drug: PEG2b
  • Drug: Ribavirin
  • Drug: Placebo to Boceprevir
• Active Comparator: Boceprevir Arm
  PEG2b (1.5 µg/kg/week SC) plus ribavirin (600- 1400 mg/day divided BID PO) for 4 weeks followed by boceprevir (800 mg TID PO) plus PEG2b/R for 44 weeks with 24 weeks post-treatment follow-up
  Interventions:

  • Drug: PEG2b
  • Drug: Ribavirin
  • Drug: Boceprevir

Inclusion Criteria:

• >=18 and <=65 years of age
• Body weight >=40 and <=125 kg
• Documented history of HIV infection for greater than 6 months prior to Day 1
• On an optimized anti-retroviral treatment regimen (OTR) with stable HIV disease with CD4 >=200 cells/uL and HIV-1 RNA viral load <50 copies/mL
• Documented chronic hepatitis C (CHC) genotype 1 infection (greater than 6 months prior to Day 1)
• Use of acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months or longer after treatment
• Liver biopsy with histology consistent with CHC and no other etiology

Exclusion Criteria:

• Participants who received prior treatment for hepatitis C other than herbal remedies except those with known hepatotoxicity
• Coinfected with hepatitis B virus (Hepatitis B surface antigen (HBsAg) positive) and/or demonstrating signs and symptoms consistent with concomitant infection
• Evidence of decompensated liver disease
• Participants who have changed their anti-retroviral regimen within the last 3 months prior to Day 1 or had first initiated anti-retroviral therapy within the last 6 months prior to Day 1
• Use of certain HIV medications will not be allowed. Medications will be reviewed by the Investigator
• History of clinically significant opportunistic infections (except oral thrush) within the last year prior to Day 1
• Current evidence of substance abuse within 3 years of the Screening Visit
• History of a clinical diagnosis within the past 6 months of substance abuse prior to Day 1
• Participants receiving opiate agonist substitution therapy but not enrolled in an opiate substitution maintenance program
• History of marijuana use deemed excessive by the Investigator
• Infected with HIV-2
• Use of any HIV protease inhibitor without the coadministration of ritonavir within one month of Day 1 and throughout the period of the trial
• Participants receiving any of the following medication(s) within 2 weeks prior to the Day 1 visit: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, and quinidine), ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, triazolam, and orally administered midazolam.

Key Laboratory Exclusion Criteria:

• Hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve trial entry requirements):

  • Hemoglobin <11 g/dL for females and <12 g/dL for males
  • Neutrophils <1500/mm^3 (blacks/African-Americans: <1200/mm^3)
  • Platelets <100,000/mm^3
  • Direct bilirubin >1.5 x ULN (upper limit of normal) of the laboratory reference range. Total bilirubin >1.6 mg/dL unless history of Gilbert's disease or antiretroviral regimen contains atazanavir. If Gilbert's disease is the proposed etiology, this must be documented in the participant's chart

• Alpha fetoprotein (AFP):

  • AFP >100 ng/mL OR
  • AFP 50 to 100 ng/mL (requires a liver ultrasound and participants with findings suspicious for hepatocellular carcinoma are excluded)