Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05685AM2)(COMPLETED)

NCT00845065 | Completed Phase 3 Results DMC

• 1 other identifier: P05685
• Study Type: interventional
• Target: 202
• Locations: 0 countries
• Sites: N/A

Brief Summary

Based on previous experience with peginterferon alfa-2b/ribavirin in combination with boceprevir, the combination with peginterferon alfa- 2a/ribavirin and boceprevir is expected to be safe and well tolerated. Given the wide utilization of both peginterferons and the clear benefit of the addition of boceprevir to peginterferon alfa-2b/ribavirin, it is important to demonstrate the safety and efficacy of boceprevir in combination with peginterferon alfa-2a/ribavirin.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• Sustained Virologic Response (SVR) Rate in Full Analysis Set (FAS) Population.

  SVR rate was the percentage of participants treated with at least one dose of study medication (PEG2a, Ribavirin, or Boceprevir/Placebo) who had achieved SVR. SVR was defined as undetectable Hepatitis C Virus-Ribonucleic Acid (HCV RNA).

  Follow-up Week 24

Secondary Outcomes (4)

• SVR Rate in the Modified Intent-to-Treat (mITT) Population

  Follow-up Week 24

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

  Day 1 to Treatment Week 12

• Number of Participants With Undetectable HCV-RNA at Follow-up Week 12

  Follow-up Week 12

• Mean Log Change From Baseline to TW 4 in Viral Load by Visit

  From Baseline to TW 4

Study Arms (2)

Arm 1 (Control Arm)

PLACEBO COMPARATOR

Peginterferon alfa-2a (180 μg/week subcutaneously \[SC\]) plus ribavirin (1000 to 1200 mg/day orally \[PO\]) for 4 weeks followed by placebo (800 mg three times a day \[TID\] PO, using placebo matching SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up.

Other: Placebo; Biological: Peginterferon alfa-2a; Drug: Ribavirin

Arm 2 (Boceprevir Arm)

EXPERIMENTAL

Peginterferon alfa-2a (180 μg/week subcutaneously \[SC\]) plus ribavirin (1000 to 1200 mg/day orally \[PO\]) for 4 weeks followed by boceprevir (800 mg three times a day \[TID\] PO, using SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up.

Drug: Boceprevir; Biological: Peginterferon alfa-2a; Drug: Ribavirin

Interventions

Boceprevir DRUG

800 mg, using SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks

Also known as: SCH 503034

Arm 2 (Boceprevir Arm)

Placebo OTHER

800 mg, using placebo matching SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks

Arm 1 (Control Arm)

Peginterferon alfa-2a BIOLOGICAL

Peginterferon alfa-2a, pre-filled syringes, given 180 μg/week subcutaneously (SC) for 48 weeks

Also known as: Pegasys®

Arm 1 (Control Arm); Arm 2 (Boceprevir Arm)

Ribavirin DRUG

Ribavirin 200-mg capsules, weight-based dosing * \<75 kg, 1000 mg/day orally (PO), divided twice daily (BID) * \>=75 kg, 1200 mg/day PO, divided BID for 48 weeks

Also known as: SCH 18908

Arm 1 (Control Arm); Arm 2 (Boceprevir Arm)

Eligibility Criteria

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

You may qualify if:

• Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.
• During the qualifying regimen, subjects must have either:
• A documented undetectable Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) within 30 days of the end-of-treatment and a subsequent detectable HCV-RNA during follow-up OR
• A documented decline in HCV-RNA by \>=2 log10 after 12 weeks of treatment.
• Subject must have previously documented chronic hepatitis C genotype 1 infection.
• Subject must have a liver biopsy with histology consistent with chronic hepatitis C infection and no other etiology.
• Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months with no findings suspicious for hepatocellular carcinoma (HCC).
• Subject must be \>=18 years of age.
• Subject must weigh between 40 kg and 125 kg.
• Subject and subject's partner(s) must each agree to use acceptable methods of contraception.
• Subjects must be willing to give written informed consent.

You may not qualify if:

• Subject will be excluded from entry if ANY of the criteria listed below are
• met:
• Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive) and/or demonstrating signs and symptoms consistent with co-infection.
• Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
• Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening.
• Treatment with any investigational drug within 30 days of the randomization visit in this study.
• Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study.
• Evidence of decompensated liver disease.
• Diabetic and/or hypertensive subjects with clinically significant ocular examination findings.
• Pre-existing psychiatric condition(s).
• Clinical diagnosis of substance abuse.
• Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study.
• Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin).
• Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are or who intend to become pregnant during the study period.
• Any other condition which, in the opinion of a physician, would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Flamm SL, Lawitz E, Jacobson I, Bourliere M, Hezode C, Vierling JM, Bacon BR, Niederau C, Sherman M, Goteti V, Sings HL, Barnard RO, Howe JA, Pedicone LD, Burroughs MH, Brass CA, Albrecht JK, Poordad F. Boceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection. Clin Gastroenterol Hepatol. 2013 Jan;11(1):81-87.e4; quiz e5. doi: 10.1016/j.cgh.2012.10.006. Epub 2012 Oct 10.

  PMID: 23064222 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

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; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: February 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: April 7, 2017
• Results First Posted: February 2, 2012

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share