The anti-hepatitis C virus (HCV) effect and safety of 3 different oral doses of Debio 025 in combination with peginterferon alpha 2a (peg-IFNα2a) 180 g/week was investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase IIa study in treatment naïve chronic HCV patients. Doses of 200, 600, and 1000 mg/day of Debio 25 in combination with peg-IFNα2a 180 g/week for 4 weeks were compared to monotherapy with either Debio 025 1000 mg/day or peg-IFNα2a 180 g/week. In the treatment groups combining peg-IFNα2a and the 2 higher Debio 025 doses (600 mg and 1000 mg), mean log10 HCV RNA levels after 4 weeks of treatment decreased by – 5.07 ± 1.73 and – 5.09 ± 1.91 log10 IU/mL, respectively. Mean reduction of HCV RNA levels in the peg-IFNα2a and Debio 025 1000 mg monotherapy groups was respectively – 3.56 ± 2.37 and – 2.87 ± 2.28 log10 IU/mL. In patients with genotype 1 and 4, response to the 600 and 1000 mg combination treatments showed a continuous decay in viral load; HCV RNA reductions, which were significantly different (Holm-Bonferroni adjusted p-values < 0.02) from either monotherapy group, reached – 4.61 ± 1.88 and – 4.75 ± 2.19 log10 IU/mL at week 4, respectively. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with peg-IFNα2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1000 mg/day). Conclusion: Results confirm that Debio 025 has a potent activity against the 4 most prevalent HCV genotypes and an additive effect on HCV RNA reduction at the dose of 600 and 1000 mg/day when combined with peg-IFN2a in patients with genotype 1 and 4.
The cyclophilin inhibitor Debio 025 combined with peg-IFN2a significantly reduces viral load in treatment naïve hepatitis C patients
MAZZELLA, GIUSEPPE;
2009
Abstract
The anti-hepatitis C virus (HCV) effect and safety of 3 different oral doses of Debio 025 in combination with peginterferon alpha 2a (peg-IFNα2a) 180 g/week was investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase IIa study in treatment naïve chronic HCV patients. Doses of 200, 600, and 1000 mg/day of Debio 25 in combination with peg-IFNα2a 180 g/week for 4 weeks were compared to monotherapy with either Debio 025 1000 mg/day or peg-IFNα2a 180 g/week. In the treatment groups combining peg-IFNα2a and the 2 higher Debio 025 doses (600 mg and 1000 mg), mean log10 HCV RNA levels after 4 weeks of treatment decreased by – 5.07 ± 1.73 and – 5.09 ± 1.91 log10 IU/mL, respectively. Mean reduction of HCV RNA levels in the peg-IFNα2a and Debio 025 1000 mg monotherapy groups was respectively – 3.56 ± 2.37 and – 2.87 ± 2.28 log10 IU/mL. In patients with genotype 1 and 4, response to the 600 and 1000 mg combination treatments showed a continuous decay in viral load; HCV RNA reductions, which were significantly different (Holm-Bonferroni adjusted p-values < 0.02) from either monotherapy group, reached – 4.61 ± 1.88 and – 4.75 ± 2.19 log10 IU/mL at week 4, respectively. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with peg-IFNα2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1000 mg/day). Conclusion: Results confirm that Debio 025 has a potent activity against the 4 most prevalent HCV genotypes and an additive effect on HCV RNA reduction at the dose of 600 and 1000 mg/day when combined with peg-IFN2a in patients with genotype 1 and 4.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
