Rizedisben in Minimally Invasive Surgery: A Nonrandomized Clinical Trial.

Abstract

Importance Fluorescence-guided surgery aims to improve intraoperative identification of vital structures. Rizedisben is a myelin-binding fluorophore that fluoresces in the blue light (370-425 nm) spectrum to improve intraoperative nerve identification. Objective To determine the optimal safe and clinically effective dose of rizedisben for sustained intraoperative fluorescence of nerve structures. Design, Setting, and Participants A single-arm, open-label, phase 1 study was conducted in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP) at an urban academic cancer center in New York City between January 2023 and October 2024. Using a dose escalation design, increasing doses of rizedisben were administered after safety was assessed at each level until a clinically effective dose was determined. The obturator nerve served as the reference nerve for measuring fluorescence intensity. Eligible patients were 18 years old and older, diagnosed with prostate cancer, and scheduled for RALP. Patients were recruited in preoperative clinic visits once deemed eligible for the study. Those with prior pelvic surgery or radiation, known central or peripheral nervous system disease, current use of neurotoxic medications, recent exposure to phototoxic drugs, or serious kidney or liver dysfunction were excluded. Interventions Rizedisben was intravenously administered intraoperatively 30 minutes prior to visualization of the obturator nerve. Main Outcomes and Measures Safety was assessed through 45 postoperative days. Fluorescence was measured via subjective intraoperative scoring and by post hoc objective image analysis. Clinically effective dose was defined as achieving sustained fluorescence of the obturator nerve in 3 or more of 5 patients in 2 consecutive cohorts, provided fewer than 20% of patients experienced grade 2 or greater toxicity. Sustained fluorescence was defined as moderate or better fluorescence for 90 minutes or longer. At the clinically effective dose, fluorescence assessments of the neurovascular bundles were included. Results Thirty-eight patients (median [IQR] age, 61.5 [57.8-66.3] years) enrolled in and completed the trial. Dosing was escalated from 0.25 to 3.0 mg/kg. There was 1 grade 2 adverse event (rash) possibly attributable to rizedisben. Sustained fluorescence of the obturator nerve was achieved in all patients at 3.0 mg/kg. Prostate neurovascular bundles demonstrated evidence of fluorescence in 8 of 9 (89%) patients at 3.0 mg/kg. Conclusions and Relevance In this phase 1 trial of rizedisben, the 3.0-mg/kg dose was shown to be generally well tolerated and clinically effective. At this dose, there was excellent sustained fluorescence of the obturator nerves, and the neurovascular bundles were visualized in 8 of 9 patients. Based on these data, we are designing phase 2 studies with rizedisben for additional indications. Trial Registration ClinicalTrials.gov Identifier: NCT04983862.