Evaluating the Effectiveness of Boceprevir, Pegylated-Interferon Alfa 2b and Ribavirin in Treating Hepatitis C Virus (HCV) Infection in Adults With HIV and HCV Infection
Condition: HIV Infections; Hepatitis C
MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis
Intervention: Pegylated-Interferon Alfa 2b (PEG-IFN); Ribavirin (RBV); Boceprevir (BOC)
Intervention description: 1.5 mcg/kg subcutaneously (SC) once a week (based on participant's weight at entry) for up to 48 weeks depending on cirrhosis status and, in Group A, Week 8 HCV viral response.; 800-1400 mg orally per day with food (based on participant's weight at entry) for up to 48 weeks depending on cirrhosis status and, in Group A, Week 8 HCV viral response.; 800 mg orally every 8 hours with food from Week 5 to up to Week 48 depending on cirrhosis status and, in Group A, Week 8 HCV viral response
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 262.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Hepatitis C virus (HCV) infection is a leading cause of death and illness in people with
      HIV-1. At the time the study was designed, the standard treatment for people with HIV-1 and
      HCV coinfection included two drugs: pegylated-interferon alfa 2b (PEG-IFN) and ribavirin
      (RBV). The purpose of this study was to evaluate the effectiveness of giving boceprevir (BOC)
      together with standard treatment in treating HCV infection in people with HIV-1 and HCV
      coinfection.
    

Eligibility criteria:

        Inclusion Criteria (Groups A and B):

          -  Men and women 18 years of age or older

          -  Presence of chronic HCV infection, defined by presence of plasma or serum HCV RNA in a
             participant with HCV antibody for at least 180 days, two documented HCV RNA positive
             results greater than 180 days apart, or positive HCV RNA with biopsy demonstrating
             chronic hepatitis. More information on this criterion can be found in the protocol.

          -  Serum or plasma HCV RNA level 10,000 IU/mL or greater obtained within 42 days prior to
             study entry.

          -  Screening HCV genotype 1 performed within 6 months prior to study entry.

          -  Liver biopsy or HCV FibroSURE™ test within 104 weeks prior to study entry with
             interpretation consistent with chronic HCV infection. If a liver biopsy HCV FibroSURE™
             test had not been performed within 104 weeks prior to study entry, then either a
             biopsy or HCV FibroSURE™ test must have been obtained prior to enrollment. The cut-off
             value for the FibroSURE™ test was 0.74, where greater than 0.74 was interpreted as
             cirrhosis. More information on this criterion can be found in the protocol.

          -  Alpha feto protein (AFP) levels less than 50. If 50 or greater, they must have had a
             liver imaging study (e.g., ultrasound, computed tomography [CT] scan, magnetic
             resonance imaging [MRI] showing no evidence of hepatocellular carcinoma.

          -  HIV-1 infection. More information on this criterion can be found in the protocol.

          -  Currently not on any antiretroviral therapy (ART) for at least 4 weeks immediately
             prior to entry or on stable ART for at least 8 weeks prior to study entry using a dual
             NRTI backbone PLUS one of the following: EFV, RAL, LPV/RTV 400/100 mg twice daily,
             ATV/RTV, DRV/RTV 600/100 mg twice daily. Breaks in therapy for a maximum of 14 days
             were allowed. Dose modifications or changes in drugs during the 8 weeks prior to study
             entry were permitted unless the change in drug was due to treatment failure. More
             information on this criterion can be found in the protocol.

          -  CD4+ T-cell count greater than 200 cells/mm^3 obtained within 42 days prior to study
             entry.

          -  For participants on ART, screening plasma HIV-1 RNA less than 50 copies/mL obtained
             within 42 days prior to study entry. For participants not on ART, plasma HIV-1 RNA
             less than 50,000 copies/mL obtained within 42 days prior to study entry.

          -  The following laboratory values within 42 days prior to entry:

               -  Absolute neutrophil count (ANC) 1000/mm^3 or greater,

               -  Hemoglobin greater than 12 g/dL for men and greater than 11 g/dL for women,

               -  Platelet count greater than 80,000 per mm^3,

               -  Creatinine less than 1.5 mg/dL,

               -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT),
                  alkaline phosphatase (ALT)/serum glutamic pyruvic transaminaseless (SGPT) less
                  than or equal to 10 x the upper limit of normal (ULN),

               -  Direct bilirubin less than 1.5 mg/dL,

               -  International normalized ratio (INR) less than 1.5,

               -  Serum lipase less than or equal to 1.5 x ULN,

               -  Thyroid stimulating hormone (TSH) within normal range, unless accompanied by
                  thyroid profile consistent with normal thyroid function.

          -  For female participants of reproductive potential, a negative serum or urine pregnancy
             test with a sensitivity of at least 50 mIU/mL performed within 42 days prior to study
             entry. More information on this criterion can be found in the protocol.

          -  All participants must have agreed not to participate in a conception process (e.g.,
             active attempt to become pregnant or to impregnate, sperm donation, in vitro
             fertilization).

          -  When participating in sexual activity that could lead to pregnancy, participants must
             have agreed to use at least two reliable methods of contraception simultaneously while
             receiving protocol-specified medications, and for 6 months after stopping the
             medications. Such methods include:

               -  Condoms (male or female) with a spermicidal agent,

               -  Diaphragm or cervical cap with spermicide,

               -  Intrauterine device (IUD),

               -  Tubal ligation.

        More information on this criterion can be found in the protocol.

          -  Participants not of reproductive potential were eligible without requiring the use of
             contraceptives. More information on this criterion can be found in the protocol.

          -  Ability and willingness of participant to provide written informed consent.

        Exclusion Criteria (Groups A and B):

          -  Known allergy/sensitivity or any hypersensitivity to components of study drugs or
             their formulation.

          -  Evidence of decompensated liver disease manifested by the presence of or history of
             ascites, variceal bleeding, or hepatic encephalopathy. If hepatic cirrhosis was
             determined by liver biopsy (Stage 4 Metavir or Stage 5, 6 Ishak) or by imaging, then
             participants had to be no more than Child-Pugh Class A and have a Child-Pugh-Turcotte
             (CPT) score of 6 or less. More information on this criterion can be found in the
             protocol.

          -  Other known causes of significant liver disease including chronic or acute hepatitis
             B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency.

          -  Infection with any HCV genotype other than genotype 1, or mixed genotype infection.

          -  Uncontrolled or active depression or other psychiatric disorder such as untreated.
             Grade 3 psychiatric disorder or Grade 3 disorder not amenable to medical intervention
             that in the opinion of the site investigator might have precluded tolerability or
             safety of study requirements. Individuals with suicidal ideation or history of a
             suicidal attempt in the last 5 years prior to enrollment were excluded.

          -  History of uncontrolled seizure disorders.

          -  Serious illness including malignancy, active coronary artery disease within 24 weeks
             prior to study entry, or other chronic medical conditions that in the opinion of the
             site investigator may have precluded completion of the protocol.

          -  Presence of active or acute AIDS-defining opportunistic infections within 12 weeks
             prior to study entry. More information on this criterion can be found in the protocol.

          -  History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to
             hemolysis.

          -  History of major organ transplantation with an existing functional graft.

          -  History of autoimmune processes including Crohn's disease, ulcerative colitis, severe
             psoriasis, or rheumatoid arthritis that may be exacerbated by IFN use.

          -  Breastfeeding.

          -  Male participants with pregnant sexual partner.

          -  Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage
             colony-stimulating factor (GM-CSF) within 14 days prior to study entry.

          -  Use of systemic corticosteroids, lovastatin, simvastatin, interferon gamma, tumor
             necrosis factor(TNF)-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid,
             ganciclovir or hydroxyurea within 14 days prior to study entry.

          -  Previous use of any HCV protease or polymerase inhibitor.

          -  Active drug or alcohol use or dependence that, in the opinion of the site
             investigator, would have interfered with adherence to study requirements.

          -  Serious illness requiring systemic treatment and/or hospitalization within 42 days
             prior to entry.