Clinical trial NCT01483742: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-12-01
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety: Incidence of adverse events
timeFrame: 48 weeks
measure: Pharmacokinetics (PK): Area under the concentration-time curve (AUC)
timeFrame: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
measure: Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test
timeFrame: 48 weeks
Secondary outcomes:
measure: Emergence of viral resistance: HCV RNA gene sequence variations
timeFrame: From baseline to Week 48
measure: Virologic response: HCV RNA levels
timeFrame: approximately 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Anaheim
country: United States
state: California
city: Coronado
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: DeLand
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: New Orleans
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Hillsborough
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: San Antonio
country: United States
state: Texas
city: Fitzroy
country: Australia
state: South Australia
city: Melbourne
country: Australia
state: Victoria
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montpellier
country: France
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Chorzów
country: Poland
city: Myslowice
country: Poland
city: Warszawa
country: Poland
city: Wrocław
country: Poland
city: Bratislava
country: Slovakia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: