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

NCT00959699 | Completed Phase 2 Results DMC

• 2 other identifiers: P05411MK-3034-025
• Study Type: interventional
• Target: 99
• Locations: 0 countries
• Sites: N/A

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

Keywords

coinfection; protease inhibitor; HIV

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Sustained Viral Response (SVR) at Follow-up Week 24 (FW24) Among Randomized Participants Who Received At Least One Dose of Trial Medication

  SVR24 is defined as undetectable plasma hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks after the end of all study treatment. If there was no value in the FW24 visit window, the closest value available chronologically after this window was used; if a value was still missing after that, the value from Follow-up Week 12 (FW12) was used. HCV-RNA is detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.

  Up to Week 72

Secondary Outcomes (5)

• Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control)

  Up to Week 72

• Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24

  Up to Week 12

• Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12)

  Up to Week 60

• Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4)

  Baseline and Week 4

• Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound

  Up to Week 72

Study Arms (2)

PegIFN-2b + RBV

PLACEBO COMPARATOR

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.

Drug: PegIFN-2b; Drug: RBV; Drug: Placebo to Boceprevir

PegIFN-2b + RBV + Boceprevir

ACTIVE COMPARATOR

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.

Drug: PegIFN-2b; Drug: RBV; Drug: Boceprevir

Interventions

PegIFN-2b DRUG

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

Also known as: SCH 054031, MK-4031, Pegylated interferon alfa-2b, Peginterferon alfa-2b

PegIFN-2b + RBV; PegIFN-2b + RBV + Boceprevir

RBV DRUG

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

Also known as: Ribavirin

PegIFN-2b + RBV; PegIFN-2b + RBV + Boceprevir

Placebo to Boceprevir DRUG

Placebo to boceprevir (orally, three times per day)

PegIFN-2b + RBV

Boceprevir DRUG

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

Also known as: SCH 503034, MK-3034, Victrelis

PegIFN-2b + RBV + Boceprevir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 23768747 DERIVED

MeSH Terms

Conditions

HIV Infections; Hepatitis C; Coinfection

Interventions

peginterferon alfa-2b; Ribavirin; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: August 17, 2009
• Study Start: November 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: October 1, 2012
• Last Updated: April 7, 2017
• Results First Posted: August 30, 2013

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share