Phase 2a Trial of AR-501 for Lung Infections in CF Now Fully Enrolled
Top-line results of ongoing trial expected early next year
The Phase 2a clinical trial testing Aridis Pharmaceuticals’ experimental inhaled therapy AR-501 for chronic lung infections in people with cystic fibrosis (CF) is fully enrolled.
AR-501, designed to be given once a week, can be self-administered within minutes using a hand-held nebulizer that delivers the medication directly to the lungs.
“We worked diligently through the pandemic to enroll patients and are very pleased to reach this key milestone for our Phase 2a study of AR-501 in CF patients,” Hasan Jafri, MD, chief medical officer at Aridis, said in a company press release.
“Our focus is now on data gathering from the clinical trial centers. We anticipate reporting top-line results in the first quarter of 2023,” Jafri said.
Trial testing self-administered therapy in CF patients
CF is characterized by the production and accumulation of thick and sticky mucus, especially in the lungs, which creates an ideal environment for opportunistic bacterial infections.
More than 80% of CF patients become chronically infected with Pseudomonas aeruginosa bacteria by the age of 18. Infections caused by Staphylococcus aureus and non-tuberculosis mycobacterium also are increasingly prevalent.
In the past, antibiotics were used extensively to treat bacterial infections. This, however, has led to resistant bacterial strains, which are less responsive to treatments and contribute to exacerbating disease progression.
Also known as panaecin, AR-501 is an inhaled form of gallium citrate, an iron-like molecule that’s believed to suppress iron-dependent metabolic functions in bacteria, including those involved in infection and antibiotic resistance.
With its distinct mechanism from antibiotics, AR-501 has broad anti-microbial activity, including against bacteria, fungal, and mycobacterial species that commonly colonize the lungs of people with CF. The company believes that the therapy has the potential to be effective against the antibiotic-resistant bacteria that lead to chronic infections in CF.
According to the therapy’s website, previous preclinical studies showed that AR-501 suppressed bacteria growing in mature biofilms — sticky microorganism layers that are highly resistance against anti-microbial agents — and prevented biofilm formation.
In addition, a single inhalation of AR-501 protected mice with bacterial lung infections from disease symptoms and extended the animals’ survival. The therapy also was protective when combined with antibiotics.
Aridis launched its two-part Phase 1/2a trial (NCT03669614) in late 2018. It was designed to test single and multiple ascending doses of AR-501 against a placebo in healthy adults — the Phase 1 part — and multiple doses alone in CF patients with chronic lung infections in its Phase 2a part.
Data from the Phase 1 part, which involved 48 healthy volunteers, showed the therapy was safe and well-tolerated. The reported adverse events were mild to moderate in severity, with no serious, severe, or life-threatening side effects among participants.
The Phase 2a part sought to enroll 39 CF patients at 24 clinical centers in the U.S. These participants were divided into four groups.
In three of them, patients were randomly assigned to receive three weekly multiple ascending doses of AR-501 at 6.4 mg, 20 mg, or 40 mg, or a placebo. In the remaining group, patients were randomly assigned to three weekly doses of AR-501 — at those same doses — or a placebo. All were followed for 28 days, or just short of one month, after last dose.
The therapy is being developed in collaboration with the Cystic Fibrosis Foundation, and received orphan drug designation in the U.S. and in Europe for lung infections in CF patients. It also received fast track and qualified infectious disease product designations in the U.S. for the same indication.