eP812 - A Phase 3, Multicenter, Open-Label, Randomized, Placebo-Controlled Trial, for Ureteral Identification Using Pudexacianinium Chloride (ASP5354) in Patients Undergoing Abdominopelvic Surgery

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Purpose/Background: Identification of ureters during complex abdominal, retroperitoneal, and pelvic surgery is critical for preventing iatrogenic injury. Ureteral stenting or retrograde injection of materials is invasive and can increase risk of urologic complications. Here we describe the clinical application of a novel, noninvasive, intravenously (IV) injected fluorescent imaging agent, pudexacianinium chloride (ASP5354), to support ureteral visualization and identification during minimally invasive and open procedures.

ASP5354 is a novel iodine-free chemical entity with hydrophilic properties via conjugation with cyclodextrin. When administered IV, it is excreted into the urine through the kidneys. Photo-optically, ASP5354 fluorescence is indistinguishable from that of indocyanine green (ICG), with absorption at 780 nm and emission at 820 nm, and may be visualized using a near infrared fluorescence (NIR-F) visualization system. NIR-F visualization systems cleared for use with ICG in laparoscopic (Stryker 1688 Advanced Imaging Modalities (AIM) 4K Platform) and open (Stryker SPY-PHI) procedures allow ureteral visualization under both white light (WL) and NIR-F imaging modes. ASP5354, when used with the NIR-F imaging mode, may facilitate visualization of the ureter during minimally invasive or open abdominopelvic surgery.Methods/Interventions: Two phase 3 randomized, open-label, single IV dose studies in the US are ongoing (NCT05754333 and NCT05999747), with another international study in the planning stage. Ureter conspicuity under WL versus NIR-F will be compared during abdominopelvic surgery in participants with normal renal function or mild renal impairment for the primary analysis, and in participants with moderate or severe renal impairment for secondary analyses. The primary endpoint will be ureter conspicuity for WL versus NIR-F scored by the investigator using the 5-point Likert scale. The studies will also include assessment by blinded independent central review. Patients will include adults undergoing minimally invasive or open abdominopelvic surgeries where ureteral identification is required. Adolescents with normal renal function or mild renal impairment will be included (NCT05754333 only). Adult patients with normal renal function or mild renal impairment will be randomly assigned to 2 arms: a WL/NIR-F arm or a WL only arm. There is no randomization for adult patients with moderate or severe renal impairment or adolescent participants, and all of these participants will be allocated to the WL/NIR-F arm. Recruitment is ongoing.Results/Outcomes: In a phase 1 study mean plasma terminal elimination half-life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administrationIn. No drug related adverse events were identified. In the phase 2 study, 1.0 and 3.0 mg pudexacianinium provided ureteral visualization for the duration of minimally invasive, laparoscopic colorectal procedures and was safe and well tolerated. A dose of 3.0 mg was chosen for the current studies.
Current phase 3 data is undergoing accrual and analysis and is not available for update, however, will share video content from phase 2 study.Conclusion/

Discussion: The available nonclinical and clinical data collected to date indicates that the use of ASP5354with NIR-F imaging technologies is a promising technique that offers noninvasive, real-time ureter visualization in participants undergoing minimally invasive and open abdominopelvic surgery.Puexacianinium (ASP 5354) illuminates the right ureter during laparoscopic right colon resection