US-based Arrowhead Research has dosed the first patient in Part B of a Phase I clinical trial of its RNAi-based drug candidate ARC-AAT to treat liver disease associated with the rare genetic disorder alpha-1 antitrypsin deficiency (AATD).
Recently, the company has secured orphan drug designation from the US Food and Drug Administration (FDA) for ARC-AAT to treat AATD.
Currently, the company is enrolling patients at a single centre in Australia and intends to open additional sites for enrolment in Europe, pending regulatory permission to proceed.
The company intends to complete patient enrolment in this Phase I trial by the end of this year.
Arrowhead chief operating officer Bruce Given said: "Dosing the first alpha-1 patient with ARC-AAT is a milestone for Arrowhead and for patients with AATD.
"The goal of treatment with ARC-AAT is to halt progression and possibly reverse the liver injury and fibrosis associated with AATD, which currently has no approved therapy short of liver transplant. This is becoming a larger clinical problem that we believe ARC-AAT holds great potential to address.
"We would also like to thank the Alpha-1 Foundation and The Alpha-1 Project, who have agreed to help support the development of ARC-AAT through funding and assistance with patient recruitment."
The ongoing, multi-centre, randomised, placebo-controlled, double-blind, single dose-escalation, first-in-human Phase I trial is designed to evaluate the safety, tolerability and pharmacokinetics of ARC-AAT and the effect on circulating AAT levels.
The trial has been enrolling in dose groups of six participants each, with participants randomised at a ratio of 2:1 to receive a single intravenous injection of either ARC-AAT or placebo.
The Phase I trial includes two parts: Part A in healthy volunteers, which has been completed, and Part B will be conducted in patients with PiZZ genotype AATD.
The company said that dosing in patients begins at the highest dose level used in healthy volunteers and then continued dose escalation may proceed under the protocol.
The study evaluates participants for 28 days following dosing, with additional follow-up if needed every two weeks until AAT levels return to baseline.