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

Hepatitis C, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01483742
• Other study ID #: NP27946
• Secondary ID: 2011-004129-28
• Status: Completed
• Phase: Phase 2
• First received: November 30, 2011
• Last updated: July 28, 2016
• Start date: April 2012
• Est. completion date: September 2013

Study information

• Verified date: July 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• RO5024048
1000 mg orally bid, 24 weeks
• danoprevir
100 mg orally bid, 24 weeks
• peginterferon alfa-2a [Pegasys]
180 mcg weekly, 24 weeks
• ribavirin
1000-1200 mg/kg/day orally in two divided doses, 24 weeks
• ritonavir
100 mg orally bid, 24 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  New Zealand,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of adverse events		48 weeks	No
Primary	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	No
Primary	Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test		48 weeks	No
Secondary	Emergence of viral resistance: HCV RNA gene sequence variations		From baseline to Week 48	No
Secondary	Virologic response: HCV RNA levels		approximately 1 year	No