P-1191. A Phase 3b, Open-label, Single-arm Study in Adolescent and Adult Female Participants to Evaluate Clinical Symptom Improvement and Safety of Gepotidacin During Treatment of Uncomplicated Urinary Tract Infections (uUTIs)

Abstract Background uUTIs can be painful and disrupt patients’ lives; thus, rapid symptom relief is a priority. Gepotidacin, a recently approved, novel, first-in-class triazaacenaphthylene oral antibacterial, was non-inferior to nitrofurantoin in two Phase 3 uUTI trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]), and superior in EAGLE-3, with an acceptable safety profile; however, clinical response at 24h was not assessed. Methods This Phase 3b, open-label, single-arm, multicenter US study (NCT06597344) assessed uUTI symptom relief with oral gepotidacin (1500mg; twice daily for 5 days; Fig 1). Females aged ≥ 12 years with urinary nitrite or pyuria, and with ≥ 2 uUTI symptoms (listed in Fig 1) were eligible for the study. Each symptom was rated 0–3 (none–severe) and summed for a total clinical symptom score (CSS; range 0–12). Participants (pts) attended an in-person baseline (BL) visit (Day [D]1) and 6 telephone calls at 24h, 48h, 72h, 96h, D10 and D28 post BL. The primary objective was to assess clinical symptom improvement (CSI; decrease from BL in total CSS of ≥ 1 point, without requiring other antibacterials) with gepotidacin at 24h. Secondary and exploratory objectives were to assess CSI at 48h, 72h, 96h, and D10, clinical symptom resolution (CSR; total CSS decrease from BL to 0, without requiring other antibacterials) at 24h, 48h, 72h, 96h, and D10, and safety until D28. Results Of 97 pts enrolled, 90 were clinically evaluable (CE) at 24h (CE24 [primary analysis] population; defined in Fig 2). Mean (standard deviation) BL total CSS was 7.6 (2.11). In the CE24 population, 54.4% had CSI at 24h (Fig 2). Subsequently, 79.8% (CE48, N=89), 90.0% (CE72, N=90), and 86.5% (CE96, N=89) of CE pts had CSI at 48h, 72h, and 96h, respectively, increasing to 95.6% at D10 (CE120, N=90). CSR steadily increased to 90.0% at D10 (CE120). Severity of each individual symptom decreased by 24h (Fig 3). Adverse events (AEs) were mostly gastrointestinal and mild/moderate in severity; no pts had serious AEs (Table). Conclusion Gepotidacin demonstrated a rapid and sustained clinical response, with > 50% of participants experiencing symptom improvement in 1 day of treatment and nearly 80% in 2 days. By Day 10, 90% of participants had achieved symptom resolution. An acceptable safety profile was reported. Funding: GSK (study 219575). Disclosures Marcela Ramírez, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Kalpana Gupta, MD, GSK: Advisor/Consultant|Innotive Diagnostics: Advisor/Consultant|Iterum Therapeutics: Advisor/Consultant|Qiagen Inc.: Advisor/Consultant|UpToDate: Royalties|Utility Therapeutics: Advisor/Consultant Jazmín Díaz-Regañón, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Rudrani Banerjee, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Jagriti Bablani, MSc, GSK: Employee Salim Janmohamed, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company)