Healthy Volunteers Do Well in AR-501 Trial for Chronic Lung Infections

AR-501, an inhaled treatment candidate for chronic lung infections in people with cystic fibrosis (CF), has been deemed safe and well-tolerated in healthy volunteers, results from the first part of a Phase 1/2a clinical trial show.

The trial’s safety monitoring committee (SMC) and a data safety monitoring board (DSMB) have recommended that all doses tested in this first part of the trial now proceed to the Phase 2a segment, which will test AR-501 in adult CF patients with chronic Pseudomonas aeruginosa lung infections.

Results from the second part are expected in late 2021.

“We look forward to advancing to the Phase 2a stage of the study evaluating adult cystic fibrosis patients, with results expected in [second half of] 2021,” Vu Truong, PhD, CEO of Aridis Pharmaceuticals, the company developing AR-501, said in a press release.

AR-501 is an inhaled formulation of gallium citrate intended as a weekly and self-administered therapy delivered directly to the lungs with the help of a hand-held nebulizer. This non-antibiotic, antimicrobial, small molecule very closely resembles iron, binding to iron receptors and disrupting iron-dependent processes in microbes such as those key to infection and antibiotic resistance.

In preclinical studies, AR-501 has demonstrated effectiveness against a wide range of bacteria, including antibiotic-resistant strains, and improved the efficacy of multiple antibiotics. Also, few bacteria were resistant to this agent.

A recent Phase 2 trial (NCT02354859), funded by the Cystic Fibrosis Foundation and led by researchers at the University of Washington, found that an intravenous formulation of gallium is safe and improves lung function in CF patients. But this formulation needs to be administered in a five-day continuous infusion, which is burdensome to patients.

The weekly, self-administration of AR-501 is expected to address these issues, and to potentially deliver higher doses of gallium to the lungs.

The ongoing Phase 1/2a trial (NCT03669614), also funded by the CF Foundation, is investigating ascending doses of this therapy — 6.4 mg, 20 mg, and 40 mg gallium — first in 48 healthy volunteers.

In the now-completed Phase 1 part, healthy volunteers were included in six groups, with those in the first three groups receiving a single administration of a low, medium, or high dose, and the latter three receiving multiple rounds of AR-501 also at low, medium, or high doses. In each group, six patients were randomly assigned the active treatment, and two others received a placebo.

Results showed that AR-501 aerosols were well-tolerated in this group of healthy volunteers, with no serious, severe, or life-threatening adverse events (side effects) reported in patients receiving single or multiple doses.

All adverse events were mild to moderate in severity and resolved. Most of these events were found in similar proportions across patients taking AR-501 and those receiving a placebo.

Also, some volunteers experienced temporary improvements in lung function, but these effects were not dose-dependent and were seen in both placebo and AR-501 groups.

“We know that a recent Phase 2 clinical study showed that intravenous, 5-day continuous infusion of gallium is safe and effective in improving lung functions of cystic fibrosis patients,” said Truong. “Our current data is extremely exciting as it shows that gallium is also well tolerated when delivered directly to the lungs in a more convenient, once-per-week, inhaled form that is likely capable of achieving substantially higher lung exposure than the intravenous route.”

These positive findings have prompted the SMC and a DSMB from the CF Foundation to support that all doses tested in this first part now proceed to the Phase 2a portion of the trial. This part will include 48 adult CF patients with lung infections who also will receive the treatment in single and multiple ascending doses.

AR-501 has been named orphan drug in the U.S. and European Union, and received fast track and qualified infectious diseases product designations from the U.S. Food and Drug Administration for the treatment of lung infections in CF patients.