NEW YORK (GenomeWeb) – Arrowhead Research announced that it has filed an investigational new drug application to begin two Phase IIb, multi-dose trials of its siRNA-based hepatitis B therapy ARC-520.
ARC-520 comprises two distinct siRNAs targeting highly conserved genomic regions across the major HBV genotypes, and is formulated with a proprietary delivery technology called dynamic polyconjugates. It is currently in a Phase IIa trial that is testing doses ranging from 1 mg/kg to 4 mg/kg in chronic HBV patients.
According to Arrowhead, the Phase IIb studies will test multiple doses of ARC-520 in combination with either entecavir or tenofovir, two direct-acting antiviral drugs, in chronic HBV patients.
One trial, dubbed Heparc-2002, will include patients who are negative for hepatitis B e-antigen (HBeAg) at screening. The other, called Heparc-2003, will include patients who are positive for HBeAg at screening.
The primary objective of the trials is to determine the decline of HBV surface antigen, a known market of active infection, in response to treatment.
Secondary objectives are to assess measures of safety and tolerability and to evaluate multi-dose pharmacokinetics of ARC-520 in patients with chronic HBV infection when co-administered with a fixed dose of entecavir or tenofovir, in addition to other exploratory safety and pharmacodynamic objectives, the company said.
Arrowhead said it plans to also submit additional clinical trial authorization applications for ARC-520 with regulatory authorities in Europe and Asia.