A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted DANOPREVIR and RO5024048 in Different Combinations in Null Responder or Treatment Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis

A Study of Ritonavir-Boosted Danoprevir and RO5024048 in Different Combinations in Null Responder or Treatment-Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis

Sponsors

Lead sponsor: Hoffmann-La Roche

Source Hoffmann-La Roche
Brief Summary

This open-label, parallel cohort study will evaluate the safety, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients, and with RO5024048 added to the combination treatment in prior null responder patients with chronic hepatitis C genotype 1 or 4 and compensated cirrhosis. All patients will receive danoprevir 100 mg orally twice daily (bid) , ritonavir 100 mg orally bid, Pegasys 180 mcg subcutaneously weekly and ribavirin 1000-1200 mg/kg/day orally. Prior non-responders will receive RO5024048 1000 mg orally bid additionally. Anticipated time on study treatment is 24 weeks.

Overall Status Completed
Start Date April 2012
Completion Date September 2013
Primary Completion Date September 2013
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Safety: Incidence of adverse events 48 weeks
Pharmacokinetics (PK): Area under the concentration-time curve (AUC) Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test 48 weeks
Secondary Outcome
Measure Time Frame
Emergence of viral resistance: HCV RNA gene sequence variations From baseline to Week 48
Virologic response: HCV RNA levels approximately 1 year
Enrollment 43
Condition
Intervention

Intervention type: Drug

Intervention name: RO5024048

Description: 1000 mg orally bid, 24 weeks

Arm group label: Combination with RO5024048

Intervention type: Drug

Intervention name: danoprevir

Description: 100 mg orally bid, 24 weeks

Intervention type: Drug

Intervention name: peginterferon alfa-2a [Pegasys]

Description: 180 mcg weekly, 24 weeks

Intervention type: Drug

Intervention name: ribavirin

Description: 1000-1200 mg/kg/day orally in two divided doses, 24 weeks

Intervention type: Drug

Intervention name: ritonavir

Description: 100 mg orally bid, 24 weeks

Eligibility

Criteria:

Inclusion Criteria:

- Adult patients, 18 to 65 years of age inclusive

- Chronic hepatitis C, genotype 1 or 4

- Cohort 1: Treatment-naïve for hepatitis C

- Cohort 2: Prior null responder to treatment with approved doses of pegylated interferon plus ribavirin

- Liver biopsy confirming cirrhosis

- Compensated cirrhosis (Child-Pugh A)

Exclusion Criteria:

- Pregnant or lactating women or male partners of women who are pregnant

- History or presence of decompensated liver disease (ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices)

- Cohort 2: Patients who discontinued previous pegylated interferon plus ribavirin treatment due to reasons other than null response

- History of clinically significant cardiovascular or cerebrovascular disease

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Trials Study Director Hoffmann-La Roche
Location
facility
| Birmingham, Alabama, 35294, United States
| Anaheim, California, 92801, United States
| Coronado, California, 92118, United States
| La Jolla, California, 92037, United States
| Long Beach, California, 90807, United States
| DeLand, Florida, 32720, United States
| Miami, Florida, 33136, United States
| Orlando, Florida, 32803, United States
| Atlanta, Georgia, 30308, United States
| Atlanta, Georgia, 30309, United States
| New Orleans, Louisiana, 70112, United States
| Detroit, Michigan, 48202-2689, United States
| Hillsborough, New Jersey, 08844, United States
| New York, New York, 10021, United States
| San Antonio, Texas, 78215, United States
| Fitzroy, South Australia, 3065, Australia
| Melbourne, Victoria, 3124, Australia
| Vancouver, British Columbia, V6Z 2C7, Canada
| Toronto, Ontario, M5G 2C4, Canada
| Montpellier, 34094, France
| Auckland, 1142, New Zealand
| Christchurch, 8140, New Zealand
| Chorzów, 41-500, Poland
| Myslowice, 41-400, Poland
| Warszawa, 02-507, Poland
| Wrocław, 51-149, Poland
| Bratislava, 833 05, Slovakia
Location Countries

Australia

Canada

France

New Zealand

Poland

Slovakia

United States

Verification Date

July 2016

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Combination without RO5024048

Arm group type: Experimental

Description: Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients

Arm group label: Combination with RO5024048

Arm group type: Experimental

Description: RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients

Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov