Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1.
BACKGROUND
New direct-acting antiviral agents are currently being developed to treat chronic HCV. The efficacy and safety of daclatasvir combined with peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized, double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection.


METHODS
Japanese patients who were treatment-naive (n=25) or prior null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir recipients with a protocol-defined response (HCV RNA<15 IU/ml at week 4 and undetectable at week 12) were treated for 24 weeks; placebo recipients and patients without a protocol-defined response were treated for 48 weeks.


RESULTS
Sustained virological response at 24 weeks post-treatment (SVR24) was achieved by 89% and 100% of treatment-naive patients receiving daclatasvir 10 mg and 60 mg, respectively, versus 75% in placebo recipients. Virological failure was more frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone. The most commonly reported adverse events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus and diarrhoea. Three patients discontinued treatment due to anaemia.


CONCLUSIONS
Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated. The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder populations and will be evaluated in a Phase III clinical trial.
Musashino Red Cross Hospital, Tokyo, Japan. nizumi@musashino.jrc.or.jp.
Namiki
N
Izumi
Osamu
O
Yokosuka
Norifumi
N
Kawada
Yukio
Y
Osaki
Kazuhide
K
Yamamoto
Michio
M
Sata
Hiroki
H
Ishikawa
Tomoko
T
Ueki
Wenhua
W
Hu
Fiona
F
McPhee
Eric A
EA
Hughes
Hiromitsu
H
Kumada
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011759:Pyrrolidines; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D000095022:Interferon Lambda
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011759:Pyrrolidines; D011994:Recombinant Proteins; D012254:Ribavirin; D014633:Valine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C549273:daclatasvir; C100416:peginterferon alfa-2a