US-based BioCryst Pharmaceuticals has dosed the first subject in a Phase IIa proof of concept clinical trial of orally administered BCX4161 in patients with hereditary angioedema (HAE).
The randomised, placebo-controlled, two-period cross-over design trial also called as OPuS-1 (Oral ProphylaxiS-1) will assess 400mg of BCX4161 given three times daily for 28 days in 25 HAE patients with a high-frequency of attacks.
The main aim of the study is to assess BCX4161's degree of efficacy in reducing the frequency of angioedema attacks, as well as the safety and tolerability of 28 days of BCX4161 treatment.
BioCryst chief medical officer William Sheridan said the company is seeking to get the results of OPuS-1, the first trial of an oral kallikrein inhibitor in HAE patients.
"The safety, tolerability, drug exposure and kallikrein inhibition achieved in the Phase 1 healthy volunteer trial of BCX4161 strongly support its further evaluation in HAE patients," Sheridan said.
"OPuS-1 is another step toward our goal of improving HAE patients' lives by dramatically changing the management of this disease."
The trial, which is being carried out at about four centres in Germany, will assess the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of BCX4161.
In the OPuS-1 trial each subject will be given BCX4161 and placebo in two separate 28-day periods, with the order of therapy randomised, placebo followed by BCX4161 or BCX4161 followed by placebo.
The primary efficacy endpoint of the trial is the mean attack frequency in each period, while other efficacy measures include average severity of attacks, the number of attack-free days and quality of life.
According to the company, BCX4161 is a novel, selective inhibitor of plasma kallikrein in development for prevention of attacks in patients with HAE.
By inhibiting plasma kallikrein, BCX4161 suppresses production of bradykinin, which is the mediator of acute swelling attacks in HAE patients.
BCX4161 exhibited potent and selective inhibition of plasma kallikrein and a favourable safety profile in in vitro and in vivo studies.
BioCryst's core development programme comprises BCX4161 and a next-generation oral inhibitor of plasma kallikrein for hereditary angioedema; peramivir, a viral neuraminidase inhibitor for the treatment of influenza; and BCX4430, a broad spectrum antiviral for haemorrhagic fevers.
Scientists at BioCryst are currently finalising the evaluation of multiple potent and specific second generation oral kallikrein inhibitors in order to develop compounds with potential for once daily dosing for the treatment of HAE.
The company said one to three candidates are expected to enter preclinical development before the end of this year.
Image: Swollen right hand in a female patient during a hereditary angioedema attack. Photo: courtesy of LucyHAE.