A Study of Ritonavir-Boosted Danoprevir (RO5190591) in Combination With Pegasys and Ribavirin in Patients With Chronic Hepatitis C Genotype 1

NCT01185860 | Completed Phase 1

• 2 other identifiers: NP226602009-012426-36
• Study Type: interventional
• Target: 59
• Locations: 3 countries
• Sites: 4

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.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability: Adverse events, ECG, laboratory parameters

  approximately 3 years

• Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2

  Days 3-9

• Antiviral activity: HCV RNA (COBAS Taqman HCV Test)

  from baseline to Day 28

Secondary Outcomes (4)

• Viral resistance development

  from baseline to Day 17

• Effects on cytochrome P450(CYP)2C9 and 3A isozymes

  from baseline to Day 17

• Virological response in prior null-responders

  from baseline to week 72

• Comparison of pharmacokinetics and antiviral activity between treatment-naïve patients and prior null-responders to standard of care treatment

  approximately 3 years

Study Arms (3)

A

ACTIVE COMPARATOR

Drug: danoprevir; Drug: peginterferon alfa-2a [Pegasys]; Drug: ribavirin

B

EXPERIMENTAL

Drug: danoprevir; Drug: peginterferon alfa-2a [Pegasys]; Drug: ribavirin; Drug: ritonavir

C

PLACEBO COMPARATOR

Drug: peginterferon alfa-2a [Pegasys]; Drug: placebo; Drug: ribavirin; Drug: ritonavir

Interventions

danoprevir DRUG

oral doses

A; B

peginterferon alfa-2a [Pegasys] DRUG

180 mcg sc once weekly

A; B; C

placebo DRUG

oral doses

C

ribavirin DRUG

1000-1200mg/day po

A; B; C

ritonavir DRUG

oral doses

B; C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

Unknown Facility

Montpellier, 34094, France

Location

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

Grafton, 1010, New Zealand

Location

Unknown Facility

Warsaw, 01-201, Poland

Location

Related Publications (3)

• 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.

  PMID: 24295986 DERIVED

• 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.

  PMID: 23872824 DERIVED

• 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.

  PMID: 21354234 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

danoprevir; peginterferon alfa-2a; Ribavirin; Ritonavir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2010
• First Posted: August 20, 2010
• Study Start: August 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

PL (1); NZ (2); FR (1)