A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C

PLoS One. 2016 Oct 17;11(10):e0164563. doi: 10.1371/journal.pone.0164563. eCollection 2016.

Abstract

Background: A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection.

Methods: Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR.

Results: A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm.

Conclusions: In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hematologic Diseases / etiology
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / adverse effects
  • Interleukins / genetics
  • Interleukins / therapeutic use*
  • Male
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / blood
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Oligopeptides
  • RNA, Viral
  • Recombinant Proteins
  • peginterferon lambda-1a
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • Interferons
  • peginterferon alfa-2a

Grants and funding

Bristol-Myers Squibb (the sponsor) designed the study in collaboration with the academic investigators (Robert Flisiak, Mitchell Shiffman, Juan Arenas, Hugo Cheinquer, and Igor Nikitin), conducted the study, collected study data, and performed statistical analyses. The sponsor, together with all authors, interpreted the data and drafted the manuscript with the assistance of a medical writer funded by the sponsor. Authors employed by the sponsor (Yuping Dong, Khurram Rana, and Subasree Srinivasan), in concert with all other authors, approved the final manuscript and made the decision to submit the manuscript for publication.