A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4)
Condition: HIV Infections; Hepatitis C; HCV Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis
Intervention: PegIFN-2b; RBV; Placebo to Boceprevir; Boceprevir
Intervention description: PegIFN-2b (1.5 μg/kg/week subcutaneously); Ribavirin (600-1400 mg/day, orally, divided into two daily doses); Placebo to boceprevir (orally, three times per day); Boceprevir (800 mg, orally, three times per day)
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 99.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: coinfection; protease inhibitor; HIV

Summary:

      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 (PegIFN-2b)
      1.5 µg/kg weekly (QW) subcutaneously (SC) plus weight-based dosing (WBD) of ribavirin (RBV)
      (600 mg/day to 1400 mg/day) PO to therapy with PegIFN-2b + RBV 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 PegIFN-2b and RBV in combination 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 PegIFN-2b/RBV, it is important to demonstrate
      the safety and efficacy of boceprevir in combination with PegIFN-2b/RBV in participants
      coinfected with HIV/HCV.

      This is a randomized, multi-center trial, double-blinded for boceprevir or placebo in
      combination with open-label PegIFN-2b/RBV 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 (Arm 1) and one experimental
      arm (Arm 2). Participants in the control arm (Arm 1) may receive boceprevir/PegIFN-2b/RBV via
      a crossover arm.
    

Eligibility criteria:

        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/µL 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)