Clinical trial NCT01331850: A Study of Danoprevir/Ritonavir and Copegus With RO5024048 and/or Pegasys in Patients With Chronic Hepatitis C
Official title: A Randomized Open-label Study to Evaluate the Sustained Virologic Response of Danoprevir/Ritonavir and Copegus in Combination With RO5024048 and/or Pegasys in Chronic Hepatitis C Genotype 1 Patients Who Failed Previous Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-04-08
Enrollment: 381
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, open-label, multi-center study will evaluate the sustained virological response, pharmacokinetics and safety of various combinations of danoprevir/ritonavir with Copegus plus RO5024048 and/or Pegasys in patients with chronic hepatitis C infection. Patients will be divided into 2 separate cohorts. Cohort A, previous partial responders, will be randomized to Groups 1-3 and cohort B, previous null responders, will be randomized to Groups 4-6. Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Groups 1 and 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Groups 3, 5 and 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.


Eligibility criteria: Inclusion Criteria:

* Adult patients, age 18 years and older
* Presence of hepatitis C infection, genotype 1a or 1b
* Documentation of previous treatment failure after receiving approved doses of peginterferon plus ribavirin for at least 12 weeks
* Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to study start

Exclusion Criteria:

* Infection with any hepatitis C genotype or subtype other than genotype 1a or 1b
* Patients with cirrhosis
* Patients who were discontinued from previous peginterferon plus ribavirin therapy due to reasons other than insufficient therapeutic response
* Co-infection with hepatitis B or human immunodeficiency virus (HIV)
* History or evidence of chronic liver disease other than hepatitis C

Primary outcomes:
measure: Sustained virological response (SVR) of danoprevir/ritonavir with RO5024048 and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment
timeFrame: 24 weeks
measure: Sustained virological response (SVR) of danoprevir/ritonavir with Pegasys and Copegus in patients with previous partial response to peginterferon/ribavirin treatment
timeFrame: 24 weeks
measure: Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment
timeFrame: 24 weeks
measure: Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus followed by 24 weeks of Pegasys and Copegus treatment in patients with previous null response to peginterferon/ribavirin treatment
timeFrame: 48 weeks
Secondary outcomes:
measure: Safety (Incidence of adverse events) of danoprevir, RO5024048 and Copegus
timeFrame: 48 weeks
measure: Safety (Incidence of adverse events) of danoprevir, Pegasys and Copegus
timeFrame: 48 weeks
measure: Safety (Incidence of adverse events) of danoprevir, RO5024048, Pegasys and Copegus
timeFrame: 72 weeks
measure: Virological response over time
timeFrame: 48 weeks
measure: Change in danoprevir plasma concentration
timeFrame: 24 weeks
measure: Change in RO5024048 plasma concentration
timeFrame: 24 weeks
measure: Hepatitis C virus drug resistance profile
timeFrame: 24 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Orlando
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: New Orleans
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Medford
country: United States
state: Oregon
city: Providence
country: United States
state: Rhode Island
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Darlinghurst
country: Australia
state: New South Wales
city: Kingswood
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Adelaide
country: Australia
state: South Australia
city: Melbourne
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Wien
country: Austria
city: Porto Alegre
country: Brazil
state: RS
city: Ribeirao Preto
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: La Tronche
country: France
city: Paris
country: France
city: Paris
country: France
city: Pessac
country: France
city: Vandoeuvre-les-nancy
country: France
city: Berlin
country: Germany
city: Essen
country: Germany
city: Kiel
country: Germany
city: Tübingen
country: Germany
city: Napoli
country: Italy
state: Campania
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Pisa
country: Italy
state: Toscana
city: Guadalajara
country: Mexico
city: Guadalajara
country: Mexico
city: Bydgoszcz
country: Poland
city: Czeladz
country: Poland
city: Kielce
country: Poland
city: Warszawa
country: Poland
city: Łodz
country: Poland
city: San Juan
country: Puerto Rico
city: Badalona
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Birmingham
country: United Kingdom
city: Dundee
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: