Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study.

Abstract

BACKGROUND:

SOUND-C3 was a multicentre, open-label, phase 2b study exploring the safety and efficacy of the interferon-free combination of faldaprevir (an NS3/A4 protease inhibitor), deleobuvir (BI 207127, a non-nucleoside polymerase inhibitor) and ribavirin in treatment-naive patients with chronic hepatitis C virus (HCV) genotype-1 infection. Results in patients with HCV genotype-1b and in IL28B CC genotype patients with HCV genotype-1a have been described previously. This report describes the results in IL28B non-CC genotype patients with HCV genotype-1a.

METHODS:

Patients were randomized to receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily (b.i.d.; N=26) or 600 mg three times daily (t.i.d.; N=25), and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12).

RESULTS:

In each group, five patients completed 24 weeks of treatment. SVR12 rates were 19% (5/26) and 8% (2/25) in the b.i.d. and t.i.d. groups, respectively. On-treatment breakthrough [50% (13/26) and 68% (17/25) in the b.i.d. and t.i.d. groups, respectively] was the most frequent reason for not achieving SVR12. Adverse events led to premature treatment discontinuation in six (23%) patients in the b.i.d. group and in two patients (8%) in the t.i.d. group. The majority of adverse events were mild or moderate; the most frequently reported were nausea (67%), fatigue (35%) and diarrhoea (35%).

CONCLUSION:

In this small study, the interferon-free regimen of faldaprevir, deleobuvir and ribavirin resulted in high rates of virological breakthrough and low rates of SVR12 in IL28B non-CC genotype patients infected with genotype-1a HCV (http://www.clinicaltrials.gov NCT01132313).

• Authors: Stefan Zeuzem, Parvez Mantry, Vicente Soriano, Robert J Buynak, Jean-François Dufour, Paul J Pockros, David Wright, Peter Angus, Maria Buti, Jerry O Stern, Werner Kadus, Richard Vinisko, Wulf Böcher, Federico J Mensa
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 28 Issue 8 Pg. 923-6 (Aug 2016) ISSN: 1473-5687 [Electronic] England
• PMID: 27140229 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Acrylates
• Aminoisobutyric Acids
• Antiviral Agents
• Benzimidazoles
• interferon-lambda, human
• Interleukins
• Oligopeptides
• Protease Inhibitors
• Quinolines
• RNA, Viral
• Thiazoles
• Ribavirin
• deleobuvir
• Interferons
• faldaprevir
• Proline
• Leucine

Topics

• Acrylates (administration & dosage, adverse effects)
• Adult
• Aminoisobutyric Acids
• Antiviral Agents (administration & dosage, adverse effects)
• Australia
• Benzimidazoles (administration & dosage, adverse effects)
• Drug Administration Schedule
• Drug Therapy, Combination
• Europe
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (diagnosis, drug therapy, genetics, virology)
• Humans
• Interferons
• Interleukins (genetics)
• Leucine (analogs & derivatives)
• Male
• Middle Aged
• Oligopeptides (administration & dosage, adverse effects)
• Phenotype
• Proline (analogs & derivatives)
• Protease Inhibitors (administration & dosage, adverse effects)
• Quinolines
• RNA, Viral (blood, genetics)
• Ribavirin (administration & dosage, adverse effects)
• Sustained Virologic Response
• Thiazoles (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome
• United States