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Safety and Efficacy of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Interleukin-28B CC Allele-Positive Chronic Hepatitis C Virus (HCV) Genotype 1 Participants (P07755)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01544920
First received: February 28, 2012
Last updated: April 22, 2016
Last verified: April 2016
  Purpose

The primary purpose of this study is to compare the efficacy of two boceprevir (BOC)-containing therapeutic regimens in the treatment of naïve participants with chronic hepatitis C virus (HCV) genotype 1 who have the IL28B CC allele.

The regimens differ in the treatment for participants who achieve undetectable HCV ribonucleic acid (RNA) at the end of the peginterferon alfa-2a (peg-IFN) plus ribavirin (RBV) 4 week lead-in. Participants receive either peg-IFN + RBV (Arm 1) or BOC + peg-IFN + RBV (Arm 2). The hypothesis is that Arm 2 is noninferior to Arm 1 in the proportion of participants with undetectable HCV RNA at Follow-Up (FU) Week 24.


Condition Intervention Phase
Hepatitis C, Chronic
Biological: peg-Interferon alfa-2a
Drug: Ribavirin
Drug: Boceprevir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Safety and Efficacy Study of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Chronic HCV Genotype 1 IL28B CC Subjects

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24) [ Time Frame: Up to Week 74 ] [ Designated as safety issue: No ]
    SVR24 rates were determined for all participants in Arm 1 and Arm 2. HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.


Secondary Outcome Measures:
  • Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24 [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    SVR24 rates were determined for only participants that had undetectable HCV RNA at Week 4 of treatment (Arm 1a and Arm 2a). HCV RNA viral load was determined using the Roche COBAS® AmpliPrep/COBAS® TaqMan HCV Test v1.0, which has a lower limit of quantification of 43 IU/mL.


Enrollment: 737
Study Start Date: May 2012
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1: peg-IFN + RBV
Participants received an initial 4 week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, participants with undetectable HCV RNA received open label peg-IFN + RBV for an additional 18 weeks (total of 24 weeks of peg-IFN/RBV therapy) [Arm 1a]. Participants with detectable HCV RNA at Week 4 had BOC added to the peg-IFN + RBV regimen at Week 6 and then followed the Response Guided Therapy (RGT) regimen for BOC + peg-IFN + RBV [Arm 1b].
Biological: peg-Interferon alfa-2a
peg-IFN (180 ug) was taken once weekly via subcutaneous injection.
Other Name: Pegasys™; SCH 054031
Drug: Ribavirin
RBV 200 mg tablets taken by mouth at a total daily dose of 1,000 mg (body weight <75 kilograms [kg]) or 1,200 mg (body weight ≥75 kg) with total daily dose divided into 2 dosings.
Other Name: Rebetol™; 018908
Drug: Boceprevir
Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.
Other Name: SCH 503034; Victrelis™
Experimental: Arm 2: BOC + peg-IFN + RBV
Participants received an initial 4-week lead-in of peg-IFN + RBV. Following HCV RNA analysis at Week 4, all participants had BOC added to the peg-IFN + RBV regimen at Week 6 regardless of HCV RNA levels. Participants who had undetectable HCV RNA at Week 4 continued on the BOC + peg-IFN + RBV regimen for an additional 20 weeks (total of 24 weeks of BOC + peg-IFN + RBV therapy) [Arm 2a]. Participants with detectable HCV RNA at Week 4 followed the RGT regimen for BOC + peg-IFN + RBV [Arm 2b].
Biological: peg-Interferon alfa-2a
peg-IFN (180 ug) was taken once weekly via subcutaneous injection.
Other Name: Pegasys™; SCH 054031
Drug: Ribavirin
RBV 200 mg tablets taken by mouth at a total daily dose of 1,000 mg (body weight <75 kilograms [kg]) or 1,200 mg (body weight ≥75 kg) with total daily dose divided into 2 dosings.
Other Name: Rebetol™; 018908
Drug: Boceprevir
Four 200 mg BOC capsules taken three times a day by mouth for a total daily dose of 2,400 mg.
Other Name: SCH 503034; Victrelis™

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is ≥ 40 kg and ≤ 125 kg.
  • Documented CHC genotype 1 with HCV RNA ≥10,000 International Units (IU)/mL
  • Has IL-28B CC allele gene
  • Has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma (non-invasive fibroscan and Fibrotest can also be used for staging of liver disease).

Exclusion Criteria:

  • Co-infection with the human immunodeficiency virus (HIV) or hepatitis B virus (Hepatitis B surface antigen [HBsAg] or HIV positive).
  • Previously treated with an interferon and ribavirin regimen or HCV direct acting antiviral regimen.
  • Treatment for hepatitis C with any investigational medication, or prior treatments with herbal remedies with known hepatotoxicity
  • Receiving any medication(s) within 2 weeks prior to the Day 1 visit that are highly dependent on Cytochrome P450 3A4 (CYP3A4/5) for clearance, and for which elevated plasma concentrations could be associated with serious and/or life-threatening events
  • Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial.
  • Evidence of decompensated liver disease or hepatocellular carcinoma (HCC)
  • Is diabetic and/or hypertensive with significant retinopathy
  • Has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction.
  • Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
  • Hemoglobin <12 g/dL for females and <13 g/dL for males
  • Neutrophils <1,500/mm^3, or <1,200/mm^3 for participants of African descent
  • Platelets <150,000/mm^3
  • Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference range.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01544920

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01544920     History of Changes
Other Study ID Numbers: P07755  2011-001345-32  MK-3034-040  CTRI/2012/12/003200  PHRR131022-000133 
Study First Received: February 28, 2012
Results First Received: April 22, 2016
Last Updated: April 22, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferons
Ribavirin
Interferon-alpha
Peginterferon alfa-2a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016