A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection

Background & Aims Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events. Methods This was a randomized, blinded, actively-controlled...

Full description

Saved in:
Bibliographic Details
Published in:Journal of hepatology 2014-12, Vol.61 (6), p.1238-1246
Main Authors: Muir, Andrew J, Arora, Sanjeev, Everson, Gregory, Flisiak, Robert, George, Jacob, Ghalib, Reem, Gordon, Stuart C, Gray, Todd, Greenbloom, Susan, Hassanein, Tarek, Hillson, Jan, Horga, Maria Arantxa, Jacobson, Ira M, Jeffers, Lennox, Kowdley, Kris V, Lawitz, Eric, Lueth, Stefan, Rodriguez-Torres, Maribel, Rustgi, Vinod, Shemanski, Lynn, Shiffman, Mitchell L, Srinivasan, Subasree, Vargas, Hugo E, Vierling, John M, Xu, Dong, Lopez-Talavera, Juan C, Zeuzem, Stefan
Format: Article
Language:English
Subjects:
Antiviral Agents - therapeutic use
Dose-Response Relationship, Drug
Double-Blind Method
Drug Therapy, Combination
Efficacy
Female
Gastroenterology and Hepatology
Genotype
Hepacivirus - genetics
Hepatitis C, Chronic - blood
Hepatitis C, Chronic - drug therapy
Hepatitis C, Chronic - genetics
Humans
Interferon-alpha - therapeutic use
Interferons - therapeutic use
Interleukins - therapeutic use
Male
Middle Aged
Polyethylene Glycols - therapeutic use
Recombinant Proteins - therapeutic use
Ribavirin - therapeutic use
RNA, Viral - blood
Safety
SVR
Treatment Outcome
Treatment-naive
Type III interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background & Aims Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events. Methods This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1–4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks. Results Rates of undetectable HCV-RNA at week 12 (complete early virologic response [cEVR]; primary end point) were significantly higher in GT1,4 patients receiving Lambda vs. alfa (170/304, 56% vs. 38/103, 37%); with similar cEVR rates for GT2,3 (80/88, 91% vs. 26/30, 87%). Rates of undetectable HCV-RNA at week 4 were significantly higher on 180 μg (15/102, 15% GT1,4; 22/29, 76% GT2,3) and 240 μg (17/104, 16% GT1,4; 20/30, 67% GT2,3) Lambda than alfa (6/103, 6% GT1,4; 9/30, 30% GT2,3). Sustained virologic responses (post-treatment week 24) were comparable between Lambda and alfa for GT1,4 (37–46% Lambda; 37% alfa) and GT2,3 (60–76% Lambda; 53% alfa). Aminotransferase and/or bilirubin elevations were the primary dose-limiting abnormalities for Lambda; a sponsor-mandated 240 to 180 μg dose reduction was therefore implemented. Serious adverse events were comparable (3–13% Lambda; 3–7% alfa). Grade 3–4 haemoglobin, neutrophil, and platelet reductions were lower on Lambda than alfa. Among alfa patients, 28/133 (21%) had peginterferon and 31/133 (23%) had ribavirin dose reductions for haematologic abnormalities vs. 0/392 and 8/392 (2%) on Lambda. Lambda demonstrated fewer musculoskeletal (16–28% vs. 47–63%) and influenza-like events (8–23% vs. 40–46%) than alfa. Conclusion Lambda was associated with improved or similar rates of virologic response with fewer extrahepatic adverse events than alfa in chronic HCV infection.
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2014.07.022