Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C.
Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 mug subcutaneous injections. The median change in HCV RNA from baseline to day 15 was -1.09 log(10) (range, -2.08 to -0.46) in the placebo and peginterferon alfa-2a group; -3.99 log(10) (range, -5.28 to -1.26) in the telaprevir group, and -5.49 log(10) (range, -6.54 to -4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group.


CONCLUSIONS
This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2a.
Forestier
Nicole
N
Saarland University Hospital, Homburg, Germany. innfor@uniklinikum-saarland.de
Reesink
Hendrik W
HW
Weegink
Christine J
CJ
McNair
Lindsay
L
Kieffer
Tara L
TL
Chu
Hui-May
HM
Purdy
Susan
S
Jansen
Peter L M
PL
Zeuzem
Stefan
S
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D000637:Transaminases / Q000097:blood
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C486464:telaprevir; D000637:Transaminases; C019741:asparagine-oxo-acid aminotransferase; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a