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Clinical Trial
. 2016 May;64(5):1011-1019.
doi: 10.1016/j.jhep.2015.12.018. Epub 2015 Dec 29.

Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)

Henry L Y Chan  1 , Sang Hoon Ahn  2 , Ting-Tsung Chang  3 , Cheng-Yuan Peng  4 , David Wong  5 , Carla S Coffin  6 , Seng Gee Lim  7 , Pei-Jer Chen  8 , Harry L A Janssen  9 , Patrick Marcellin  10 , Lawrence Serfaty  11 , Stefan Zeuzem  12 , David Cohen  13 , Linda Critelli  13 , Dong Xu  13 , Megan Wind-Rotolo  14 , Elizabeth Cooney  15 ; LIRA-B Study Team
Affiliations
Clinical Trial

Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)

Henry L Y Chan et al. J Hepatol. 2016 May.

Abstract

Background & aims: Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection.

Methods: Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%.

Results: Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise.

Conclusions: On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762.

Keywords: Human; Immunomodulatory therapy; Viral hepatitis.

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