Apeiron Biologics has begun a Phase I trial for inhalation of APN01, a recombinant human angiotensin-converting enzyme 2 developed to treat Covid-19 patients by neutralising SARS-CoV-2 in the lungs and mitigating lung damage caused by the infection.
The double-blind, placebo-controlled, dose-escalation study plans to enroll about 40 healthy volunteers in Austria to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of inhaled APN01.
The primary study objective is the evaluation of safety and tolerability of single ascending doses (SADs) and multiple ascending doses (MADs) of inhaled APN01 when administered via a jet nebuliser in healthy subjects. Secondary objectives include the maximum tolerated dose and the effect of APN01 on key pharmacodynamic biomarkers of the renin-aldosterone-angiotensin system (RAAS).
Romana Gugenberger, CMSO of Apeiron Biologics, said: “This study will form the basis not only for the treatment of Covid-19 with inhaled APN01 but enables further development strategies in chronic respiratory diseases with high unmet medical need such as Chronic Obstructive Pulmonary Disease (COPD) and Pulmonary Arterial Hypertension (PAH).”
Peter Llewellyn-Davies, CEO of Apeiron Biologics, said: “With the data from our concluded Phase II trial with APN01, recently supported by highly encouraging efficacy results in preclinical models, we are confident that inhalation with APN01 can deliver substantial benefits for patients suffering from Covid-19 infections. This is the third clinical trial dedicated to the multi-armed initiative of developing APN01 into vital therapy options in Covid-19. We look forward to the results of the ongoing trials which could pave the way for the future treatment of Covid-19 with APN01.”
Professor Dr Markus Zeitlinger, Department of Clinical Pharmacology at the Medical University of Vienna and principal investigator of the trial, said: “Preliminary data from ongoing studies with inhalation of ACE2 based therapeutics show high efficacy in SARS-CoV-2 preclinical models. Delivery of the drug candidate directly to the respiratory tract should block viral entry into the lung cells and control inflammation. Importantly, APN01 may also be suitable against infections with variants of SARS-CoV-2 as already shown preclinically.”
Apeiron’s previously completed Phase II trial with intravenously administered APN01 demonstrated significant improvement in certain parameters of the Renin Angiotensin Aldosterone System (RAAS) with APN01 treatment compared to placebo. Data also suggested that APN01 will confer greatest therapeutic benefit to patients with lower WHO-CPS (World Health Organization Clinical Progression Scale) scores.
In parallel, APN01 is to be administered intravenously in a US Phase II trial conducted by the Vanderbilt University Medical Center (VUMC), Nashville, USA, and supported and funded by the National Institutes of Health (NIH). The four-arm, randomised, double-blinded, placebo-controlled trial is enrolling approximately 1,600 Covid-19 patients at more than 50 sites in the United States.
Image credit: CDC
