The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients.
The anti-hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-alpha2a (PEG IFN-alpha2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-alpha2a 180 microg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 microg/week PEG IFN-alpha2a. In patients with genotypes 1 and 4, the 600- and 1,000-mg combination treatments induced a continuous decay in viral load that reached -4.61 +/- 1.88 and -4.75 +/- 2.19 log(10) IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by -5.91 +/- 1.11 and -5.89 +/- 0.43 log(10) IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-alpha2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day).


CONCLUSIONS
These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-alpha2a.
Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
Robert
R
Flisiak
Saya V
SV
Feinman
Maciej
M
Jablkowski
Andrzej
A
Horban
Wieslaw
W
Kryczka
Małgorzata
M
Pawlowska
Jenny E
JE
Heathcote
Giuseppe
G
Mazzella
Carmen
C
Vandelli
Valérie
V
Nicolas-Métral
Pierre
P
Grosgurin
Jorge S
JS
Liz
Pietro
P
Scalfaro
Hervé
H
Porchet
Raf
R
Crabbé
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016572:Cyclosporine; C100416:peginterferon alfa-2a; C499715:alisporivir