Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results.

Abstract

BACKGROUND:

Faldaprevir (BI 201335) and deleobuvir (BI 207127) are direct-acting antiviral agents under development for the treatment of chronic HCV infection. This article describes the final results of the Phase Ib SOUND-C1 study that evaluated the interferon-free oral combination of faldaprevir, deleobuvir and ribavirin in 32 treatment-naive patients infected with HCV genotype 1.

METHODS:

Patients were randomized to receive deleobuvir 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon-α2a/ribavirin to week 24 or 48.

RESULTS:

At week 4, 73% (11/15) and 100% (17/17) of patients in the deleobuvir 400 mg and 600 mg groups achieved HCV RNA<25 IU/ml, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the deleobuvir 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon-α2a/ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%) and asthenia (31%); these were severe in approximately 3% of patients.

CONCLUSIONS:

Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen. Clinical trials.gov number NCT01132313.

• Authors: Stefan Zeuzem, Tarik Asselah, Peter Angus, Jean-Pierre Zarski, Dominique Larrey, Beat Müllhaupt, Ed Gane, Marcus Schuchmann, Ansgar W Lohse, Stanislas Pol, Jean-Pierre Bronowicki, Stuart Roberts, Keikawus Arasteh, Fabien Zoulim, Markus Heim, Jerry O Stern, Gerhard Nehmiz, George Kukolj, Wulf O Böcher, Federico J Mensa
• Journal: Antiviral therapy (Antivir Ther) Vol. 18 Issue 8 Pg. 1015-9 ( 2013) ISSN: 2040-2058 [Electronic] England
• PMID: 23558093 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Acrylates
• Aminoisobutyric Acids
• Antiviral Agents
• Benzimidazoles
• Interferon-alpha
• Oligopeptides
• Quinolines
• Recombinant Proteins
• Thiazoles
• Polyethylene Glycols
• Ribavirin
• deleobuvir
• faldaprevir
• Proline
• Leucine
• peginterferon alfa-2a

Topics

• Acrylates (adverse effects, therapeutic use)
• Aminoisobutyric Acids
• Antiviral Agents (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Therapy, Combination
• Hepacivirus (classification, drug effects, genetics)
• Hepatitis C, Chronic (drug therapy)
• Interferon-alpha (therapeutic use)
• Leucine (analogs & derivatives)
• Oligopeptides (adverse effects, therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Proline (analogs & derivatives)
• Quinolines
• Recombinant Proteins (therapeutic use)
• Ribavirin (adverse effects, therapeutic use)
• Thiazoles (adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)