Aridis Pharmaceuticals, Inc., a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, today announced it has reached an agreement with the US Food and Drug Administration (FDA) to simplify the Company's AR-501 Phase 2 trial design for the treatment of chronic lung infections associated with cystic fibrosis (CF).
After reporting (June 2020) positive Phase 1 safety data in healthy adults who were exposed to a single ascending dose (SAD) or a multiple ascending dose (MAD) regimen, Aridis proposed, and the FDA has now agreed to streamline AR-501's forthcoming Phase 2a clinical trial in CF patients, by removing the SAD and only conducting a MAD regimen. Furthermore, the FDA also concurred with the Company's proposal to expand the originally planned Phase 2a protocol design into a Phase 2a/2b study. This Phase 2a/2b design will enable seamless and efficient advancement of the study from Phase 2a into Phase 2b using the same clinical study protocol. The data from the Phase 2a will inform the dose selection and sample size expansion to achieve statistical significance in efficacy in Phase 2b.
"The change to an adaptive style clinical trial design is an important milestone for the AR-501 program as it streamlines the regulatory pathway, expedites program timeline, and maximizes overall resources," commented Vu Truong, PhD, Chief Executive Officer of Aridis Pharmaceuticals. "We look forward to initiating the Phase 2a trial in the coming months and anticipate completing the study towards the end of 2021."
About AR-501
On June 22, 2020 Aridis reported positive safety data from the healthy subjects portion of its Phase 1/2a clinical trial of an inhaled formulation of gallium citrate being evaluated for the treatment of chronic lung infections associated with cystic fibrosis. There were no reports of serious adverse events and the aerosol treatment was well tolerated. The study was designed to enroll 48 healthy adult volunteers (Phase 1) and 48 cystic fibrosis patients (Phase 2a) from approximately 18 sites in the U.S. Participants were randomized within each cohort in a 3:1 ratio of active drug to placebo. Subjects were followed for 28 days after last study dose for safety and pharmacokinetics (PK) of inhaled AR-501 in HV subjects. AR-501 or placebo was delivered by a nebulizer device. In the now-completed Phase 1 arm, 48 healthy adults were randomized and treated in 6 cohorts (of 8 subjects each) to receive either a single ascending dose (SAD, Cohorts 1, 2, and 3 [N=24]) or weekly multiple ascending doses (MAD, Cohorts 4, 5, and 6 [N=24]) of active drug at 6.4 mg gallium (Ga+3), 20 mg Ga+3 and 40 mg Ga+3 or placebo.
AR-501 is being developed in collaboration with the CF Foundation and has been granted Orphan Drug Designation (ODD), Fast Track and Qualified Infectious Disease Product (QIDP) designations by the US FDA. In addition, the European Medicines Agency (EMA) granted ODD to AR-501. Details of the Phase 1/2a clinical trial, which is a randomized, double-blinded, placebo controlled single and multiple dose-ascending trial investigating the safety and PK of inhaled AR-501 in healthy volunteers and efficacy in cystic fibrosis patients with chronic bacterial lung infections, can be viewed on www.clinicaltrials.gov using identifier NCT03669614.