A Study of Viral Response to Triple Therapy in Hepatitis C Virus-Infected Participants With Insulin Resistance Who Failed Dual Therapy (MK-3034-113)

An Open Label Study Assessing SVR and Viral Resistance Profile With Boceprevir Plus PEG-IFN Plus Ribavirin Triple Therapy in HCV-1 Infected Patients With Insulin Resistance Who Have Failed PEG-IFN Plus Ribavirin Dual Therapy

This study is being done to find out if participants with insulin resistance and hepatitis C virus genotype 1 (HCV GT1) infections who failed dual therapy with peginterferon alfa (PegIFN) + ribavirin (RBV) will benefit from the addition of boceprevir to PegIFN + RBV (triple therapy).

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: boceprevir; Biological: PegIFN-2b; Drug: RBV

• Study Type: Interventional
• Phase: Phase 4

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:

• Quantifiable serum hepatitis C virus-ribonucleic acid (HCV-RNA)
• Hepatitis C virus genotype 1
• Homeostasis Model of Assessment - Insulin Resistance (HOMA IR) > 2.5 in two determinations made 4 weeks apart (the first HOMA evaluation is able to be made 3 weeks before screening visit)
• Previous failure to achieve SVR with PegIFN plus ribavirin given for a minimum of 12 weeks without dose reduction below 80% of the adequate doses of the two drugs
• No response, partial response, or relapse after previous therapy
• Compensated liver disease with or without histologic or non-invasive evidence of liver cirrhosis
• If heterosexually active, a female participant of childbearing potential and a non-vasectomized male participant who has a female partner of childbearing potential must agree to use 2 effective contraceptives until 6 months after therapy has ended (7 months for male subject)

Exclusion criteria:

• Coinfection with HCV genotypes other than HCV-GT1
• Evidence of decompensated liver disease
• History of ascites, hepatic encephalopathy or of bleeding varices or severe portal hypertension
• History or signs or symptoms or evidence of hepatocellular carcinoma (HCC)
• History of organ transplant
• Coinfection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• Severe psychiatric disease
• Inadequately controlled thyroid function
• Other important comorbidities (cardiovascular diseases, Type 1 diabetes or inadequately controlled type 2 diabetes, malignancies , etc)
• Substances abuse
• Alcohol intake >20 grams/day for females and >30 grams/day for males
• History of severe adverse events during previous treatment with PegIFN plus ribavirin including discontinuation of therapy for severe anemia or hematologic toxicity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Boceprevir + PegIFN-2b + RBV; All participants will start treatment with 4 weeks of PegIFN-2b subcutaneously, 1.5μg/kg per week + RBV capsules orally, at a weight-based dose between 800-1400 mg/day divided into two daily doses (double therapy). Participants without cirrhosis will then continue on the PegIFN-2b and RBV with the addition of boceprevir capsules orally, 800 mg three times per day for 32 weeks (triple therapy), and will transition back to double therapy for the final 12 weeks of treatment (48 total weeks of therapy). Participants with cirrhosis or documented as null responders will receive triple therapy for 44 weeks (48 total weeks of therapy).

Drug: boceprevir; Other Names: SCH 503034; Biological: PegIFN-2b; Other Names: SCH 054031; Peginterferon alfa-2b; PegIntron; Drug: RBV; Other Names: Rebetol; Ribavirin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with sustained virologic response (SVR) at 24 weeks after the end of 48 weeks of study treatment	Week 72

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR)	Baseline up to 8 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 15, 2013
• First Submitted That Met QC Criteria: January 15, 2013
• First Posted (Estimate): January 17, 2013

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 17, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hyperinsulinism; Hepatitis; Hepatitis A; Hepatitis C; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2b
• Other Study ID Numbers: 3034-113; 2012-002771-33 (EudraCT Number)