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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C, Chronic	Drug: RO5024048 Drug: danoprevir Drug: peginterferon alfa-2a [Pegasys] Drug: ribavirin Drug: ritonavir	Phase 2


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

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Ritonavir Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Safety: Incidence of adverse events [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Pharmacokinetics (PK): Area under the concentration-time curve (AUC) [ Time Frame: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24 ] [ Designated as safety issue: No ]
Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Emergence of viral resistance: HCV RNA gene sequence variations [ Time Frame: From baseline to Week 48 ] [ Designated as safety issue: No ]
Virologic response: HCV RNA levels [ Time Frame: approximately 1 year ] [ Designated as safety issue: No ]


Enrollment:	43
Study Start Date:	April 2012
Study Completion Date:	September 2013
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Combination without RO5024048 Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients	Drug: danoprevir 100 mg orally bid, 24 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg weekly, 24 weeks Drug: ribavirin 1000-1200 mg/kg/day orally in two divided doses, 24 weeks Drug: ritonavir 100 mg orally bid, 24 weeks
Experimental: Combination with RO5024048 RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients	Drug: RO5024048 1000 mg orally bid, 24 weeks Drug: danoprevir 100 mg orally bid, 24 weeks Drug: peginterferon alfa-2a [Pegasys] 180 mcg weekly, 24 weeks Drug: ribavirin 1000-1200 mg/kg/day orally in two divided doses, 24 weeks Drug: ritonavir 100 mg orally bid, 24 weeks

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483742

Show 27 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01483742 History of Changes
Other Study ID Numbers:	NP27946 2011-004129-28
Study First Received:	November 30, 2011
Last Updated:	July 28, 2016
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Fibrosis Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Pathologic Processes	Ribavirin Ritonavir Peginterferon alfa-2a Interferon-alpha Lactams Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Anti-HIV Agents Anti-Retroviral Agents Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016