Clinical trial NCT01185860: A Study of Ritonavir-Boosted Danoprevir (RO5190591) in Combination With Pegasys and Ribavirin in Patients With Chronic Hepatitis C Genotype 1
Official title: A Multiple-Dose Study To Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted RO5190591 in Combination With Peginterferon Alfa-2a Plus Ribavirin in Patients With Chronic Hepatitis C Genotype 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-08-20
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety and tolerability of danoprevir (RO5190591) plus ritonavir as compared to danoprevir alone or placebo plus ritonavir in patients with chronic hepatitis C genotype 1 receiving Pegasys (peginterferon alfa-2a) and ribavirin. Patients in cohorts will be randomized to receive either oral doses of danoprevir, or danoprevir plus ritonavir, or placebo plus ritonavir. All patients will receive Pegasys (180mcg sc once weekly) plus ribavirin (1000-1200mg/day po), with the option to continue this treatment after completion of study drug treatment. Anticipated time on study treatment is up to 12 weeks.


Eligibility criteria: Inclusion Criteria:

* Adults, 18-65 years of age
* Chronic hepatitis C genotype 1
* HCV treatment naïve, or without sustained virologic response on prior PEG-INF/RBV treatment
* Body mass index (BMI) 18 - 35 kg/m2, inclusive; minimum weight 45 kg

Exclusion Criteria:

* Liver cirrhosis
* Decompensated liver disease or impaired liver function
* Medical condition associated with chronic liver disease other than chronic hepatitis C
* Positive for hepatitis B or HIV infection at screening
* History of alcohol consumption exceeding 2 standard drinks per day when averaged over the course of a given week

Primary outcomes:
measure: Safety and tolerability: Adverse events, ECG, laboratory parameters
timeFrame: approximately 3 years
measure: Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2
timeFrame: Days 3-9
measure: Antiviral activity: HCV RNA (COBAS Taqman HCV Test)
timeFrame: from baseline to Day 28
Secondary outcomes:
measure: Viral resistance development
timeFrame: from baseline to Day 17
measure: Effects on cytochrome P450(CYP)2C9 and 3A isozymes
timeFrame: from baseline to Day 17
measure: Virological response in prior null-responders
timeFrame: from baseline to week 72
measure: Comparison of pharmacokinetics and antiviral activity between treatment-naïve patients and prior null-responders to standard of care treatment
timeFrame: approximately 3 years
Other outcomes:
Locations:
city: Montpellier
country: France
city: Christchurch
country: New Zealand
city: Grafton
country: New Zealand
city: Warszawa
country: Poland
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gane EJ, Rouzier R, Wiercinska-Drapalo A, Larrey DG, Morcos PN, Brennan BJ, Le Pogam S, Najera I, Petric R, Tran JQ, Kulkarni R, Zhang Y, Smith P, Yetzer ES, Shulman NS. Efficacy and safety of danoprevir-ritonavir plus peginterferon alfa-2a-ribavirin in hepatitis C virus genotype 1 prior null responders. Antimicrob Agents Chemother. 2014;58(2):1136-45. doi: 10.1128/AAC.01515-13. Epub 2013 Dec 2.
citation: Morcos PN, Chang L, Kulkarni R, Giraudon M, Shulman N, Brennan BJ, Smith PF, Tran JQ. A randomised study of the effect of danoprevir/ritonavir or ritonavir on substrates of cytochrome P450 (CYP) 3A and 2C9 in chronic hepatitis C patients using a drug cocktail. Eur J Clin Pharmacol. 2013 Nov;69(11):1939-49. doi: 10.1007/s00228-013-1556-y. Epub 2013 Jul 20.
citation: Gane EJ, Rouzier R, Stedman C, Wiercinska-Drapalo A, Horban A, Chang L, Zhang Y, Sampeur P, Najera I, Smith P, Shulman NS, Tran JQ. Antiviral activity, safety, and pharmacokinetics of danoprevir/ritonavir plus PEG-IFN alpha-2a/RBV in hepatitis C patients. J Hepatol. 2011 Nov;55(5):972-9. doi: 10.1016/j.jhep.2011.01.046. Epub 2011 Feb 24.