CDEB025A2306:DEB025 in protease inhibitor failure GT1 Hepatitis C

• Research type

  Research Study

• Full title

  A multicenter, single-arm trial evaluating the safety and efficacy of DEB025/Alisporivir in combination with pegylated interferon-a2a and ribavirin (peg-IFNa2a/RBV) in protease inhibitor treatment failure patients with chronic hepatitis C genotype 1

• IRAS ID

  96949

• Contact name

  Kosh Agarwal

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2011-004653-31

• ISRCTN Number

  n/a

• Research summary

  Chronic hepatitis C (HCV) genotype 1 (GT1) is recognized to be the most difficult to treat genotype where the primary goal of treatment is sustained virologic response (SVR) at 24 weeks. The standard current approved treatment in the UK is Pegylated interferon-a2a and ribavirin (pegIFN/RBV). Adding Protease inhibitors (PIs) to make a triple therapy can improve the SVR rate. However, at least 30% of PI-treated patients are expected to fail the PI-treatment and the majority of patients who fail to achieve SVR will have PI resistance-associated variants (RAV) (Merck FDA AAC Briefing Document). These PIs are also associated with increased adverse events compared to pegIFN/RBV alone and due to the short half life of the medications, the drugs require strict dosing of 3 times per day (7-9 hours apart). Patients who do not adhere to this strict regimen either due to poor medication compliance or to adverse events have a high risk of reducing efficacy and generating RAVs, which once present results in high level cross-resistance to both PIs available and may prevent effective use of others in development. DEB025 (alisporivir) is an orally available cyclophilin inhibitor that has shown potent antihepatitis C virus (HCV) activity in clinical studies with additive clinical effect when combined with pegIFN/RBV. Its mode of action is via inhibition of cellular (host) proteins that are involved in HCV replication, and therefore completely differs from the antiviral action protease inhibitors (PI) which target viral proteins. This study will evaluate the safety and efficacy of DEB025/Alisporivir in combination with pegylated interferon-a2a and ribavirin (peg-IFNa2a/RBV) in approximately 150 protease inhibitor treatment failure patients with chronic hepatitis C genotype 1. Up to 10 patients will be enrolled across 2 sites in the UK.

• REC name

  South Central - Hampshire B Research Ethics Committee

• REC reference

  12/SC/0034

• Date of REC Opinion

  6 Feb 2012

• REC opinion

  Favourable Opinion