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

Roche

Status and phase: Completed; Phase 2

Conditions: Hepatitis C, Chronic

Treatments: Drug: ritonavir; Drug: ribavirin; Drug: peginterferon alfa-2a [Pegasys]; Drug: danoprevir; Drug: RO5024048

Study type: Interventional

Funder types: Industry

Identifiers

NCT01483742

2011-004129-28 (EudraCT Number)

NP27946

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

43 participants in 2 patient groups

Combination without RO5024048

Experimental group

Description:

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

Treatment:

Drug: ritonavir

Drug: peginterferon alfa-2a [Pegasys]

Drug: danoprevir

Drug: ribavirin

Combination with RO5024048

Experimental group

Description:

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

Treatment:

Drug: ritonavir

Drug: peginterferon alfa-2a [Pegasys]

Drug: RO5024048

Drug: danoprevir

Drug: ribavirin