A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection.
BACKGROUND
Daclatasvir-containing regimens have the potential to address limitations of current regimens combining peginterferon alfa and ribavirin with first-generation protease inhibitors for treatment of chronic HCV genotype 1 infection.


METHODS
In this randomized, double-blind study, 27 Japanese treatment-naive patients received once-daily daclatasvir 10 mg or 60 mg or placebo, each combined with peginterferon alfa-2b/ribavirin; 18 prior null (n=9) or partial (n=9) responders received the same daclatasvir-containing regimens without a placebo arm. Daclatasvir recipients with protocol-defined response (HCV RNA<15 IU/ml at week 4, undetectable at week 12) were treated for 24 weeks; those without protocol-defined response and placebo recipients continued treatment to week 48.


RESULTS
Sustained virological response 24 weeks post-treatment (SVR24) was achieved by 66.7%, 90.0% and 62.5% of treatment-naive patients in the daclatasvir 10 mg, 60 mg and placebo groups, respectively. Prior non-responders had more frequent virological failure; 22.2% and 33.3% of daclatasvir 10 mg and 60 mg recipients, respectively, achieved SVR24. Adverse events were similar across groups and were typical of peginterferon alfa-2b/ribavirin. Pyrexia, headache, alopecia, decreased appetite and malaise were the most common adverse events; two daclatasvir recipients discontinued due to adverse events.


CONCLUSIONS
Daclatasvir 60 mg combined with peginterferon alfa-2b and ribavirin achieved a high rate of SVR24 in treatment-naive patients with HCV genotype 1 infection, with tolerability similar to that of peginterferon alfa-2b/ribavirin alone. However, regimens with greater antiviral potency are needed for prior non-responders.
Toranomon Hospital, Tokyo, Japan. fumitakas@toranomon.gr.jp.
Fumitaka
F
Suzuki
Joji
J
Toyota
Kenji
K
Ikeda
Kazuaki
K
Chayama
Satoshi
S
Mochida
Norio
N
Hayashi
Hiroki
H
Ishikawa
Hidetaka
H
Miyagoshi
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* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; 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; D055815:Young Adult
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011759:Pyrrolidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; D014633:Valine; C549273:daclatasvir