A Study of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591/Danoprevir) in Genotype 1 Chronic Hepatitis C Patients

A Randomized, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Tolerability and Antiviral Activity of Combination Treatment With an HCV Polymerase Inhibitor (RO5024048) and an HCV Protease Inhibitor (RO5190591) in Genotype 1 Chronic Hepatitis C Patients. INFORM 1

This 7 cohort study will evaluate the efficacy and safety of combination treatment with an HCV nucleoside polymerase inhibitor(RO5024048)and an HCV protease inhibitor(RO5190591/ITMN-191/danoprevir) in patients with chronic hepatitis C, genotype 1.Cohorts A,B,C,D and G will be treatment-naive patients, cohort E will be treatment-experienced excluding null responders, and cohort F will be null responders. Cohorts A and B will evaluate doses of 500mg po bid RO5024048 and 100mg po q8h RO5190591, alone or in combination, for up to 7 or 14 days. Cohort C will evaluate combination treatment with either 1000mg po bid RO5024048 and 100mg q8h RO5190591 or 500mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days. Cohort D will evaluate 1000mg po bid RO5024048 and 200mg q8h RO5190591 for 14 days.Cohort E will evaluate 1000mg RO5024048/600mg RO5190591 po twice daily for 14 days, and Cohorts F and G will evaluate 1000mg RO5024048/900mg RO5190591 po twice daily for 14 days. Cohorts will be tested sequentially or in parallel, if supported by appropriate safety and pharmacokinetic data.Following the last dose of study medication patients have the option of continuing treatment with Standard of care therapies. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: RO5024048; Drug: danoprevir; Drug: danoprevir; Drug: danoprevir; Drug: danoprevir; Drug: danoprevir

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, SA 5000
  • Heidelberg, Australia, 3084
  • Melbourne, Australia, 3181
• New Zealand
  • Christchurch, New Zealand, 8011
  • Grafton, New Zealand, 1150

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, 18-65 years of age;
• chronic hepatitis C, genotype 1.

Exclusion Criteria:

• decompensated liver disease, or impaired liver function;
• presence or history of non-hepatitis C chronic liver disease;
• HBsAg or HIV infection;
• history of cancer within 5 years, other than localized or in situ cancer of the skin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days
Experimental: Cohort A	Drug: RO5024048; 500mg po bid/100mg po q8h for 7 days
Experimental: Cohort C	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days
Experimental: Cohort D	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days
Experimental: Cohort E	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days
Experimental: Cohort F	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days
Experimental: Cohort G	Drug: danoprevir; 500mg po bid/100mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/100mg po q8h for 14 days\n500mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg po bid/200mg po q8h for 14 days; Drug: danoprevir; 1000mg/600mg po twice daily for 14 days; Drug: danoprevir; 1000mg/900mg po twice daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HCV RNA	At each clinic visit, throughout study
Adverse events, laboratory parameters, vital signs	At each clinic visit, throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameters;viral resistance	At intervals, throughout study

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, Elston R, Ipe D, Morcos PN, Baher L, Najera I, Chu T, Lopatin U, Berrey MM, Bradford W, Laughlin M, Shulman NS, Smith PF. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010 Oct 30;376(9751):1467-75. doi: 10.1016/S0140-6736(10)61384-0. Epub 2010 Oct 14.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: December 2, 2008
• First Submitted That Met QC Criteria: December 2, 2008
• First Posted (Estimate): December 3, 2008

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; Anti-Infective Agents; Anti-Bacterial Agents; Lactams
• Other Study ID Numbers: PP22205