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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01185860




Registration number
NCT01185860
Ethics application status
Date submitted
19/08/2010
Date registered
20/08/2010
Date last updated
2/11/2016

Titles & IDs
Public title
A Study of Ritonavir-Boosted Danoprevir (RO5190591) in Combination With Pegasys and Ribavirin in Patients With Chronic Hepatitis C Genotype 1
Scientific 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
Secondary ID [1] 0 0
2009-012426-36
Secondary ID [2] 0 0
NP22660
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - danoprevir
Treatment: Drugs - peginterferon alfa-2a [Pegasys]
Treatment: Drugs - placebo
Treatment: Drugs - ribavirin
Treatment: Drugs - ritonavir

Active comparator: A -

Experimental: B -

Placebo comparator: C -


Treatment: Drugs: danoprevir
oral doses

Treatment: Drugs: peginterferon alfa-2a [Pegasys]
180 mcg sc once weekly

Treatment: Drugs: placebo
oral doses

Treatment: Drugs: ribavirin
1000-1200mg/day po

Treatment: Drugs: ritonavir
oral doses
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability: Adverse events, ECG, laboratory parameters
Timepoint [1] 0 0
approximately 3 years
Primary outcome [2] 0 0
Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2
Timepoint [2] 0 0
Days 3-9
Primary outcome [3] 0 0
Antiviral activity: HCV RNA (COBAS Taqman HCV Test)
Timepoint [3] 0 0
from baseline to Day 28
Secondary outcome [1] 0 0
Viral resistance development
Timepoint [1] 0 0
from baseline to Day 17
Secondary outcome [2] 0 0
Effects on cytochrome P450(CYP)2C9 and 3A isozymes
Timepoint [2] 0 0
from baseline to Day 17
Secondary outcome [3] 0 0
Virological response in prior null-responders
Timepoint [3] 0 0
from baseline to week 72
Secondary outcome [4] 0 0
Comparison of pharmacokinetics and antiviral activity between treatment-naïve patients and prior null-responders to standard of care treatment
Timepoint [4] 0 0
approximately 3 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2012
Sample size
Target
Accrual to date
Final
59
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Montpellier
Country [2] 0 0
New Zealand
State/province [2] 0 0
Christchurch
Country [3] 0 0
New Zealand
State/province [3] 0 0
Grafton
Country [4] 0 0
Poland
State/province [4] 0 0
Warszawa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01185860
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01185860