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

• ClinicalTrials.gov Identifier: NCT00959699
• Recruitment Status: Completed
• First Posted: August 17, 2009
• Results First Posted: August 30, 2013
• Last Update Posted: April 7, 2017
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: July 29, 2009
• First Posted Date: August 17, 2009
• Results First Submitted Date: May 8, 2013
• Results First Posted Date: August 30, 2013
• Last Update Posted Date: April 7, 2017
• Study Start Date: November 2009
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2013)

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 [ Time Frame: Up to Week 72 ]

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.

• Original Primary Outcome Measures (submitted: August 14, 2009): To compare 24 week follow-up HCV-RNA level after treatment w/ boceprevir in combo w/ PEG2b plus ribavirin weight-based dosing to treatment with PEG2b plus ribavirin alone in adult subjects coinfected w/ HIV & previously untreated chronic HCV genotype 1 [ Time Frame: 24 weeks after treatment ]

Current Secondary Outcome Measures (submitted: July 26, 2013)

• Percentage of Participants Achieving SVR24 Among Randomized Participants Who Received At Least One Dose of Boceprevir (Experimental) or Placebo (Control) [ Time Frame: Up to Week 72 ]
  SVR24 is defined as undetectable plasma HCV-RNA 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 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.
• Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR24 [ Time Frame: Up to Week 12 ]
  EVR was defined as undetectable HCV-RNA at Treatment Week (TW) 2, 4, 8, or 12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
• Percentage of Participants With Undetectable HCV-RNA at Follow-up Week 12 (FW12) [ Time Frame: Up to Week 60 ]
  The virologic response at FW12 was considered SVR12 with an additional rule for handling missing data: participants with missing HCV-RNA assessment at FW12 but having non-missing, undetectable HCV-RNA assessments at both FW4 and FW24, were assumed to be responders for SVR12. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
• Change From Baseline in log10 HCV-RNA at Treatment Week 4 (TW4) [ Time Frame: Baseline and Week 4 ]
  This is a measure of the change in the amount of HCV-RNA in the plasma at the end of 4 weeks of treatment. HCV-RNA was detected by a nucleic acid amplification test and the lower limit of detection for this assay is 9.3 IU/mL.
• Percentage of Participants With HCV Virologic Breakthrough or Incomplete Virologic Response/Rebound [ Time Frame: Up to Week 72 ]
  Virologic breakthrough is defined as achieving undetectable HCV-RNA and subsequently having an HCV-RNA level of >1000 IU/mL. Incomplete Virologic Response/Rebound is defined as having a one 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 lower limit of detection for this assay is 9.3 IU/mL.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4)
• Official Title: A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (Protocol No. P05411)

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• HIV Infections
• Hepatitis C
• HCV Infection

Intervention

• Drug: PegIFN-2b
  PegIFN-2b (1.5 μg/kg/week subcutaneously)
  Other Names:

  • SCH 054031
  • MK-4031
  • Pegylated interferon alfa-2b
  • Peginterferon alfa-2b
• Drug: RBV
  Ribavirin (600-1400 mg/day, orally, divided into two daily doses)
  Other Name: Ribavirin
• Drug: Placebo to Boceprevir
  Placebo to boceprevir (orally, three times per day)
• Drug: Boceprevir
  Boceprevir (800 mg, orally, three times per day)
  Other Names:

  • SCH 503034
  • MK-3034
  • Victrelis

Study Arms

• Placebo Comparator: 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.
  Interventions:

  • Drug: PegIFN-2b
  • Drug: RBV
  • Drug: Placebo to Boceprevir
• Active Comparator: 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.
  Interventions:

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

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 14, 2009): 99
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Argentina, Brazil, Canada, France, Germany, Italy, Poland, Portugal, Spain, United States

Administrative Information

• NCT Number: NCT00959699
• Other Study ID Numbers: P05411; MK-3034-025 ( Other Identifier: Merck study number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: March 2017