A Study of Ritonavir-Boosted Danoprevir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients of Asian Origin With Chronic Hepatitis C Genotype 1 With or Without Cirrhosis

STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTIVIRAL ACTIVITY OF RITONAVIR-BOOSTED DANOPREVIR IN COMBINATION WITH PEGINTERFERON ALFA-2A PLUS RIBAVIRIN IN TREATMENT-NAÏVE PATIENTS OF ASIAN ORIGIN WHO HAVE CHRONIC HEPATITIS C GENOTYPE 1 WITH OR WITHOUT COMPENSATED CIRRHOSIS

This Phase II, open-label, parallel-arm study will evaluate the safety, tolerability, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) in treatment-naïve patients of Asian origin with chronic hepatitis C genotype 1. Patients will receive danoprevir 125 mg plus ritonavir 100 mg as fixed dose tablet orally twice daily in combination with weekly Pegasys 180 mcg subcutaneously and Copegus 1000-1200 mg orally daily in divided doses. Treatment duration is 12 weeks in patients without cirrhosis and 24 weeks in patients with compensated cirrhosis.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: danoprevir + ritonavir; Drug: danoprevir + ritonavir; Drug: peginterferon alfa-2a [Pegasys]; Drug: peginterferon alfa-2a [Pegasys]; Drug: ribavirin [Copegus]; Drug: ribavirin [Copegus]

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 135-710
• Taiwan
  • Chiayi County, Taiwan, 61363
  • Kaohsiung, Taiwan, 807
  • Taichung, Taiwan, 40447
  • Taipei, Taiwan, 100
  • Taoyuan, Taiwan, 333
  • Yunlin County, Taiwan, 640
• Thailand
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330
  • Chiang Mai, Thailand, 50200

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:

• Adult patients of East Asian or Southeast Asian origin, >/= 18 years of age
• Presence of chronic genotype 1 hepatitis C infection
• Treatment-naïve

Exclusion Criteria:

• History or presence of decompensated liver disease
• Presence or history of non-hepatitis C chronic liver disease
• Positive for hepatitis B or HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: with cirrhosis	Drug: danoprevir + ritonavir; 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 12 weeks; Drug: danoprevir + ritonavir; 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 24 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 mcg sc weekly, 12 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 mcg sc weekly, 24 weeks; Drug: ribavirin [Copegus]; 1000-1200 mg orally daily in divided doses, 12 weeks; Drug: ribavirin [Copegus]; 1000-1200 mg orally daily in divided doses, 24 weeks
EXPERIMENTAL: without cirrhosis	Drug: danoprevir + ritonavir; 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 12 weeks; Drug: danoprevir + ritonavir; 125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 24 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 mcg sc weekly, 12 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 mcg sc weekly, 24 weeks; Drug: ribavirin [Copegus]; 1000-1200 mg orally daily in divided doses, 12 weeks; Drug: ribavirin [Copegus]; 1000-1200 mg orally daily in divided doses, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	approximately 1.5 years
Pharmacokinetics: Area under the concentration-time curve (AUC) for danoprevir/ritonavir	up to 14 days
Antiviral activity: Change in HCV RNA levels, measured using Roche COBAS TaqMan HCV Test v2.0 for High Pure System	from baseline to Week 36/48
Antiviral activity: Proportion of patients with unquantifiable/undetectable HCV RNA during the study	approximately 1.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of viral resistance to danoprevir	approximately 1.5 years
Rapid virological response (RVR): Proportion of patients with undetectable HCV RNA at Week 4	approximately 1.5 years
Complete early virological response (cEVR): Proportion of patients with undetectable HCV RNA at Week 12	approximately 1.5 years
Sustained virological response 12 weeks after end of treatment (SVR-12), defined as unquantifiable HCV RNA 8-20 weeks after the last day of study drug administration	approximately 1.5 years
Sustained virological response 24 weeks after end of treatment (SVR-24), defined as unquantifiable HCV RNA > 20 weeks after the last day of study drug administration	approximately 1.5 years
SVR measured as HCV RNA log10 IU/mL change from baseline to Week 12	approximately 1.5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: December 11, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (ESTIMATE): December 13, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

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; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Immunologic Factors; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Ritonavir; Lactams
• Other Study ID Numbers: YV28218