Trial of Inhaled AR-501 in Treating CF Lung Infections Enrolling in US

Phase 2a study in 39 adults with CF and confirmed P. aeruginosa infection

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by Steve Bryson, PhD |

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Enrollment of adults at sites across the U.S. is continuing for a Phase 2a trial of AR-501 (gallium citrate), Aridis Pharmaceuticals‘ investigational inhaled therapy for chronic lung infections due to cystic fibrosis (CF).

As an inhaled treatment, AR-501 is intended to be self-administered weekly using a hand-held nebulizer that delivers the medication directly to the lungs.

Top-line data from the study, supported by the Cystic Fibrosis Foundation (CFF), is expected early next year, according to a company press release. Eligible CF patients can find site locations and contact information here.

AR-501 is an inhaled formulation of gallium, an iron-like metal that can disrupt the iron-dependent metabolic functions of bacteria. Tests show it can kill a broad range of bacteria, including antibiotic-resistant strains of Pseudomonas aeruginosa, a major contributor to lung disease in people with CF. A form of gallium is currently approved in the U.S. as a diagnostic agent for prostate cancer.

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Aridis reports on its website that AR-501 was able to suppress bacteria growing in mature biofilms — slimy layers of microorganisms that stick to wet surfaces and other bacteria — and prevent biofilm formation. In mice with bacterial lung infections, a single inhalation of AR-501 protected the animals from illness and extended survival. The therapy also was protective in combination with antibiotics.

A Phase 2 study (NCT02354859) conducted by the University of Washington found that a gallium formulation, administered intravenously into the bloodstream, was safe and effective in CF patients. However, this formulation requires five days of continuous infusion, which is a demanding regimen for patients.

AR-501’s once weekly inhaled formulation of gallium, given in either a single ascending dose (SAD) or a multiple ascending dose (MAD) regimen, was found to be safe and well-tolerated in 48 healthy adults participating in the Phase 1 part of Aridis’ ongoing Phase 1/2a study (NCT03669614).

Based on these safety findings, the U.S. Food and Drug Administration (FDA) agreed to simplify the trial’s Phase 2a portion by removing the SAD regimen, leaving only a MAD regimen.

This part is now enrolling up to 39 adults, ages 18–49, with CF and confirmed P. aeruginosa infection to evaluate the safety and pharmacological properties of three increasing AR-501 doses.

Initially, at each dose level, two patients will be randomly assigned to AR-501 and one to a placebo inhaler, for a total of nine CF patients. The remaining 30 participants will be randomly assigned to three doses of inhaled AR-501 or a placebo.

Based on the latest and still-blinded safety data from the ongoing study, the FDA agreed to include an optional higher dose group after enrollment of the current dose groups is complete, Aridis announced.

The agency also allowed the company to expand its planned Phase 2a study design into a combined Phase 2a/2b study, helping it to progress through each phase using the same protocol. Data from the Phase 2a portion will inform dosing decisions for the Phase 2b study, as well as determine the number of patients to recruit to achieve meaningful efficacy.

AR-501 has orphan drug status in the U.S. and in Europe, and received fast track and qualified infectious diseases product designations from the FDA as a potential treatment of CF-related lung infections.

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