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HIV InfectionsPhase 2NCT00959699

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

A Phase 2 study testing PegIFN-2b, RBV and Boceprevir in people with HIV Infections and Hepatitis C, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV Infections, Hepatitis C, HCV Infection
What is being tested?
PegIFN-2b, RBV and Boceprevir
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
99 participants
Where
No sites listed yet
Study dates
Nov 2009to Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • >=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

Who cannot join

  • 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
Show all 22Show fewer
  • 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)

About this study

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

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.

Being tested
PegIFN-2b, RBV, Placebo to Boceprevir, Boceprevir
Keywords
coinfection, protease inhibitor, HIV
Medical subject headings
HIV Infections, Hepatitis C, Coinfection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PegIFN-2bDrug

    Also called SCH 054031, MK-4031, Pegylated interferon alfa-2b, Peginterferon alfa-2b

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

  • RBVDrug

    Also called Ribavirin

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

  • Placebo to BoceprevirDrug

    Placebo to boceprevir (orally, three times per day)

  • BoceprevirDrug

    Also called SCH 503034, MK-3034, Victrelis

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

Study groups in NCT00959699
Study groupRoleWhat they receive
PegIFN-2b + RBVPlacebo comparatorPegIFN-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.
Receives: Drug: PegIFN-2b; Drug: RBV; Drug: Placebo to Boceprevir
PegIFN-2b + RBV + BoceprevirActive comparatorPegIFN-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.
Receives: Drug: PegIFN-2b; Drug: RBV; Drug: Boceprevir

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to Week 72

Secondary outcomes (5)

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

    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.

    Measured: Up to Week 72

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

    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.

    Measured: Up to Week 12

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

    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.

    Measured: Up to Week 60

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

    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.

    Measured: Baseline and Week 4

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

    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.

    Measured: Up to Week 72

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionMay 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
99 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00959699
Sponsor's protocol ID
P05411
Other IDs
MK-3034-025
Status last verified
Mar 2017
First submitted
29 Jul 2009
Last updated
7 Apr 2017
Data monitoring committee
Yes
Individual data sharing
Yes: 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

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.

    PubMed 23768747

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PegIFN-2b, RBV and Boceprevir in people with HIV Infections and Hepatitis C, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00959699, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2017.

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