WS05.06 Phase 1/2a randomized, double-blind, placebo-controlled study: safety, Pk, and Efficacy outcome measures of inhaled Gallium Citrate (AR-501) in P Aeruginosa infected Cystic Fibrosis patients

Background: AR-501, an inhaled novel iron analog disrupts microbial iron-dependent metabolic pathways, resulting in antimicrobial activity against bacteria, NTM, and fungi. This Ph1/2a study will have data readout by mid-2023 (www.clinicaltrials.gov NCT03669614). Inhaled AR-501 in HV’s was generally well tolerated once weekly for 5 weeks. Here we report the preliminary safety, PK, and exploratory efficacy results of once-weekly inhaled AR-501 for 3 doses over four weeks. Methods: A RDBPC Ph1 study in 50 HVs has been completed. Thirty-nine (39) subjects were randomized in the CF Phase 2a study, from which 30 subjects received one of the three ascending doses of AR-501, 9 received placebo. Each cohort has received a once-weekly, 3-dose regimen of inhaled active drug (6.4, 20 and 40 mg Ga) or placebo, in a 2:1 ratio and followed for 28 days after the 3rd dose. Outcome measures include safety, PK, PFTs (FEV1), microbiology, CFQ-R, and inflammatory biomarkers. Results: Phase 2a, all CF sentinel and all but 1 subject in the expanded cohort completed all 3 doses (6.4, 20 and 40 mg) in a blinded fashion. Subjects given: Low (n = 8), Medium (n = 11), High Dose (n = 11) and Placebo (n = 9). PK, efficacy and biomarker data will be reported after database lock. Safety data reviewed by an independent unblinded Data and Safety Monitoring Board (DSMB) deemed suitable for expansion to an 80 mg study group. Most AEs were mild/moderate and respiratory in nature. Nebulized AR-501 is well tolerated, with no attributable serious adverse events (SAEs). DSMB had no safety concerns. The 80 mg dosing, to include 15 subjects randomized in a 2:1 ratio. DSMB will review safety from 6 sentinel subjects prior to enrolling 9 subjects. Tabled 1Multiple Ascending Dose Adverse Event Incidence SummarySubjects with anyLow Dose Cohort (N = 5)Medium Dose Cohort (N = 3)High Dose Cohort (N = 3)Expanded Dose Cohort N = 31)AE2 (40%)1 (33.3%)2 (66.6%)24 (77.4%)Grade 3 AE1 (20%)007 (22.6%)Grade ≥4 AE0000Study drug-related AE01 (33.3%)1 (33.3%)16 (51.6%)SAE0002 (6.5%)Study drug-related SAE0000 Open table in a new tab Conclusions: AR-501 is being developed as a once-weekly aerosolized antimicrobial with broad antimicrobial activity. Inhaled AR-501 has been well tolerated when administered once weekly ×3 weeks. Ph2a safety, efficacy and biomarker data readout is due prior to ECFS meeting.