A Double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects

Authors


Abstract

Background & Aims

GSK2336805 is a HCV NS5A inhibitor for chronic hepatitis C (CHC). In a prior Phase I study, GSK2336805 was well tolerated and had an antiviral and pharmacokinetic profile suitable for once-daily administration. This 28-day, double-blind, randomized, placebo-controlled study evaluated once daily GSK2336805 60 mg alone or in combination with peginterferon alfa-2a (180 μg per week) and ribavirin (1000–1200 mg daily) (PEG/RIBA) in treatment-naive genotype 1 CHC subjects.

Methods

Five centres enrolled 16 subjects in the USA and Puerto Rico who received GSK2336805 + PEG/RIBA or placebo + PEG/RIBA.

Results

Following a single monotherapy dose of GSK2336805 on day 1, median reduction from baseline in HCV RNA was −2.96 log10 (N = 11) vs. −0.13 log10 (N = 4) for placebo. With the addition of PEG/RIBA on day 2, subjects receiving GSK2336805 exhibited greater decreases in viral load over the 28-day treatment period as compared with placebo. At day 28, median reduction from baseline was −4.86 log10 (N = 9) in the GSK2336805 + PEG/RIBA group as compared with −1.98 log10 (N = 4) in the placebo + PEG/RIBA group. At day 28, rapid virological response (RVR) occurred in 8/11 (73%) of the GSK2336805 + PEG/RIBA subjects as compared with 1/4 (25%) of the placebo + PEG/RIBA subjects. Adverse events were consistent with those reported in clinical trials of peginterferon and ribavirin, and no unique adverse events appeared to be associated with GSK2336805.

Conclusions

GSK2336805 is a potent NS5A inhibitor that showed a substantial antiviral effect as a monotherapy and in combination with peginterferon and ribavirin.

ClinicalTrials.gov Identifier: NCT01439373.

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