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

NCT ID: NCT00959699

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2012-10-31

Brief 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.

Conditions

HIV Infections; Hepatitis C; HCV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

PegIFN-2b + RBV

PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600-1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by placebo to boceprevir plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up (Control Arm). Participants who do not achieve HCV-RNA \<9.3 IU/mL by Treatment Week 24 (TW24) are eligible to cross-over and receive boceprevir along with the PegIFN-2b and RBV for up to 44 weeks.

Group Type: PLACEBO_COMPARATOR

PegIFN-2b

Intervention Type: DRUG

PegIFN-2b (1.5 μg/kg/week subcutaneously)

RBV

Intervention Type: DRUG

Ribavirin (600-1400 mg/day, orally, divided into two daily doses)

Placebo to Boceprevir

Intervention Type: DRUG

Placebo to boceprevir (orally, three times per day)

PegIFN-2b + RBV + Boceprevir

PegIFN-2b (1.5 µg/kg/week subcutaneously) plus RBV (600- 1400 mg/day, orally, divided into two daily doses) for 4 weeks followed by boceprevir (800 mg, orally, 3 times per day) plus PegIFN-2b/RBV for 44 weeks with 24 weeks post-treatment follow-up.

Group Type: ACTIVE_COMPARATOR

PegIFN-2b

Intervention Type: DRUG

PegIFN-2b (1.5 μg/kg/week subcutaneously)

RBV

Intervention Type: DRUG

Ribavirin (600-1400 mg/day, orally, divided into two daily doses)

Boceprevir

Intervention Type: DRUG

Boceprevir (800 mg, orally, three times per day)

Interventions

PegIFN-2b

PegIFN-2b (1.5 μg/kg/week subcutaneously)

Intervention Type: DRUG

RBV

Ribavirin (600-1400 mg/day, orally, divided into two daily doses)

Intervention Type: DRUG

Placebo to Boceprevir

Placebo to boceprevir (orally, three times per day)

Intervention Type: DRUG

Boceprevir

Boceprevir (800 mg, orally, three times per day)

Intervention Type: DRUG

Other Intervention Names

SCH 054031; MK-4031; Pegylated interferon alfa-2b; Peginterferon alfa-2b; Ribavirin; SCH 503034; MK-3034; Victrelis

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.

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Sulkowski M, Pol S, Mallolas J, Fainboim H, Cooper C, Slim J, Rivero A, Mak C, Thompson S, Howe AY, Wenning L, Sklar P, Wahl J, Greaves W; P05411 study investigators. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis. 2013 Jul;13(7):597-605. doi: 10.1016/S1473-3099(13)70149-X. Epub 2013 Jun 12.

Reference Type: DERIVED

PMID: 23768747 (View on PubMed)

Other Identifiers

MK-3034-025

Identifier Type: OTHER

Identifier Source: secondary_id

P05411

Identifier Type: -

Identifier Source: org_study_id