Phase 2/3 Randomized Controlled Trial on Nizaracianine Triflutate for Ureter Visualization in Abdominopelvic Surgery Patients Aged 18+

The primary objectives of this Phase 2/3 trial are to assess the **safety** and efficacy of nizaracianine triflutate, a near-infrared fluorophore, in enhancing the visualization of ureter anatomy and function during abdominopelvic surgical procedures. In Phase 2, the trial aims to define the near-optimal dose of nizaracianine for this purpose. In Phase 3, the focus is on evaluating the efficacy of nizaracianine at its near-optimal dose for improving the delineation of ureter anatomy and function, providing both technical and clinical benefits. These objectives are clinically relevant as they aim to improve surgical outcomes by enhancing the visualization of critical anatomical structures, potentially reducing the risk of ureteral injury during surgery.

The secondary objectives include: - Determining if nizaracianine reduces invasive procedures and/or dissection of surrounding tissues required for ureter identification. - Assessing if nizaracianine reduces the time required for initial ureter identification. - Evaluating if nizaracianine permits assessment of ureter integrity and function without invasive procedures. - Investigating if nizaracianine reduces or eliminates the need for ureter skeletonization/dissection. - Estimating the average time period of ureter visualization provided by the first dose of nizaracianine. - Estimating the average dose interval and number of doses preferred by surgeons for optimal visualization. - Determining if nizaracianine increases the detection of ureter injuries intraoperatively. - Assessing if nizaracianine assists in ureter repair when injury is detected intraoperatively. - Evaluating if nizaracianine reduces the overall length of surgery for specific procedure types.

The clinical trial involves a total of **168 participants** who are undergoing evaluation for the safety and efficacy of nizaracianine in enhancing ureter anatomy and function during surgery. The study population includes both **male and female subjects** aged 18 years and older, with no specific vulnerable populations selected. Participants are required to be scheduled for a medically necessary abdominopelvic surgical procedure, expected to last at least 2 hours for Phase 2, during which ureters should be visualized. The trial population was selected based on their ability to provide informed consent and having screening laboratory test results within normal limits or deemed clinically insignificant. Participants are expected to have both ureters present and functional, and women of childbearing potential must have a negative pregnancy test. The study does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase 2/3 randomized controlled semi-blinded study** designed to evaluate the safety and efficacy of **nizaracianine triflutate** in enhancing the visualization of the ureters during abdominopelvic surgical procedures. The trial involves participants aged 18 years or older who are scheduled for surgeries where ureter visualization is necessary. The study is structured to assess the safety and determine the near-optimal dose of nizaracianine triflutate, administered intravenously, to enhance ureter anatomy and function using near-infrared (NIR) fluorescent light. The trial is expected to commence recruitment on October 2, 2023, and conclude by September 30, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, surgical requirements, and laboratory test results. The trial includes follow-up visits to monitor safety and efficacy outcomes, with the end-of-study visit marking the completion of the participant's involvement. The expected duration of participant involvement is contingent upon the surgical procedure and follow-up assessments, with the maximum treatment period being one day. Conditions that may lead to early termination from the study include adverse events or withdrawal of consent.

The primary endpoints of the trial include the determination of the near-optimal dose of nizaracianine triflutate and the safety assessment across both phases. Additionally, the trial will evaluate the proportion of subjects for whom the surgeon can successfully identify the required length of the ureters with a peak signal-to-background ratio (SBR) of 1.5 or greater. Secondary endpoints focus on the efficiency of ureter identification, the time required for initial identification, and the ability to assess ureter integrity and function without invasive procedures. Exploratory endpoints will investigate the potential of nizaracianine to enhance bladder anatomy identification and provide NIR fluorescence enhancement of blood vessels in the surgical field.

The clinical trial involves the administration of **nizaracianine triflutate**, a **solution for injection** developed by Curadel Surgical Innovations Inc. This experimental medication is a near-infrared fluorophore intended for intravenous injection. The maximum daily dose is 15.0 mg, with a total dose not exceeding 15.0 mg, administered in up to three divided doses. The treatment period is limited to one day. The primary objective is to assess the safety and efficacy of nizaracianine triflutate in enhancing the visualization of ureter anatomy and function during abdominopelvic surgical procedures using near-infrared fluorescent light.

In addition to the experimental treatment, the trial utilizes **Glucose 5%**, a **solution for infusion** produced by Baxter B.V. This non-experimental treatment serves as a sterile solution for fluid replenishment or product reconstitution. The glucose solution is administered intravenously, with a maximum daily and total dose of 15 ml. The administration of this solution is also limited to a one-day treatment period. The glucose solution is used to support the experimental treatment and ensure participant safety during the trial.

Efficacy in the clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints include the determination of the near-optimal dose of **nizaracianine triflutate** in the context of an acceptable safety profile, and the proportion of subjects for whom the surgeon can successfully identify the required length of the ureters with a peak signal-to-background ratio (SBR) of 1.5 or greater. Secondary endpoints will evaluate various aspects of ureter identification and function, such as the proportion of cases where ureter identification did not require invasive procedures, the average time required for initial ureter identification, and the proportion of cases where ureter integrity and function were determined without invasive procedures. Additionally, the trial will assess the average time period of ureter visualization provided by the first dose of nizaracianine, the average dose interval, and the number of doses preferred by surgeons for optimal visualization during surgeries. Exploratory endpoints will include the proportion of cases where nizaracianine helped identify bladder anatomy and provided near-infrared (NIR) fluorescence enhancement of blood vessels in the surgical field.