Telaprevir for previously untreated chronic hepatitis C virus infection.

Abstract

BACKGROUND:

In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients.

METHODS:

In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response).

RESULTS:

Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group.

CONCLUSIONS:

Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.).

• Authors: Ira M Jacobson, John G McHutchison, Geoffrey Dusheiko, Adrian M Di Bisceglie, K Rajender Reddy, Natalie H Bzowej, Patrick Marcellin, Andrew J Muir, Peter Ferenci, Robert Flisiak, Jacob George, Mario Rizzetto, Daniel Shouval, Ricard Sola, Ruben A Terg, Eric M Yoshida, Nathalie Adda, Leif Bengtsson, Abdul J Sankoh, Tara L Kieffer, Shelley George, Robert S Kauffman, Stefan Zeuzem, ADVANCE Study Team
• Journal: The New England journal of medicine (N Engl J Med) Vol. 364 Issue 25 Pg. 2405-16 (Jun 23 2011) ISSN: 1533-4406 [Electronic] United States
• PMID: 21696307 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Oligopeptides
• RNA, Viral
• Recombinant Proteins
• Serine Proteinase Inhibitors
• Polyethylene Glycols
• telaprevir
• peginterferon alfa-2a

Topics

• Adult
• Aged
• Antiviral Agents (adverse effects, therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Logistic Models
• Male
• Middle Aged
• Oligopeptides (adverse effects, therapeutic use)
• Polyethylene Glycols (adverse effects, therapeutic use)
• RNA, Viral (blood)
• Recombinant Proteins
• Sequence Analysis, DNA
• Serine Proteinase Inhibitors (adverse effects, therapeutic use)
• Viral Load
• Young Adult