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

A Phase 3, Safety and Efficacy Study of Boceprevir/Peginterferon Alfa-2a/Ribavirin in Chronic HCV Genotype 1 IL28B CC Subjects

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Biological: peg-Interferon alfa-2a; Drug: Ribavirin; Drug: Boceprevir

• Study Type: Interventional
• Enrollment (Actual): 737
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: SCH 503034; Victrelis™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) 24 Weeks After Completing Study Treatment (SVR24)	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.	Up to Week 74

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Had Undetectable HCV RNA at Week 4 Achieving SVR24	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.	Up to Week 48

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2012
• Primary Completion (Actual): May 19, 2015
• Study Completion (Actual): May 19, 2015

Study Registration Dates

• First Submitted: February 28, 2012
• First Submitted That Met QC Criteria: March 5, 2012
• First Posted (Estimate): March 6, 2012

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: P07755; 2011-001345-32 (EudraCT Number); MK-3034-040 (Other Identifier: Merck); CTRI/2012/12/003200 (Registry Identifier: CTRI); PHRR131022-000133 (Registry Identifier: PHRR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf