Curadel Pharma has initiated the Phase 3 portion of its pivotal clinical trial evaluating ZW800-1 (nizaracianine triflutate), a first-in-class zwitterionic drug designed to highlight ureters during abdominopelvic surgery. This advancement follows the successful completion of the Phase 2 cohort, which met its primary endpoints with a favorable safety profile.
"As the first zwitterionic near infrared (NIR) fluorophore, ZW800-1 represents an important advancement in enhanced surgical imaging. The first portion of this pivotal study found that strong visual contrast enhancement of the ureters provided apparent benefit to both patient and surgeon without compromising safety," said John V. Frangioni, M.D., Ph.D., Curadel Founder and CEO.
Novel Mechanism of Action
ZW800-1 features a unique zwitterionic chemical structure that gives the drug distinctive properties critical to its function. This molecular design prevents non-specific binding to tissues and organs following injection, while facilitating efficient elimination by the kidneys into urine. Once present in urine, the drug creates visual contrast in the ureters that would not otherwise be visible.
Using a near-infrared (NIR) camera system during surgery, physicians can visualize the ureters and assess their function in real-time. This capability addresses a significant challenge in abdominopelvic surgeries, where ureter identification and preservation are critical to preventing serious complications.
Phase 2 Results and Phase 3 Design
The Phase 2 study demonstrated that ZW800-1 successfully achieved its composite primary endpoint, which included:
- Strong signal-to-background ratio
- Visualization of the required length of ureter(s)
- Favorable safety profile with no severe adverse events associated with the study drug
Based on these positive findings, the Phase 3 portion of the trial has received approval for enrollment. The study will utilize an optimal dose of only 2.5 mg, determined from earlier research.
"With confidence in our target dose, we look forward to expanding the trial to eight sites worldwide with more than 50 surgeons," Dr. Frangioni noted. "Our goal is to demonstrate for the first time that surgeons can assess ureter anatomy, function, and intactness in real time during open, laparoscopic, and robotic surgeries."
Clinical Significance
Ureter injury is a serious complication in abdominopelvic surgeries, occurring in approximately 1-5% of gynecologic and colorectal procedures. Such injuries can lead to significant morbidity, including urine leakage, infection, and potential kidney damage if not promptly identified and addressed.
Current methods for ureter identification rely primarily on surgeon experience and anatomical knowledge, with limited technological assistance. ZW800-1 represents a potential paradigm shift in surgical visualization technology by offering real-time, functional imaging of these critical structures.
Trial Expansion
The Phase 3 cohort is expected to enroll more than 300 participants across multiple international sites. This expanded trial will evaluate the drug's efficacy and safety across diverse surgical settings, including open, laparoscopic, and robotic approaches.
The clinical trial is registered on clinicaltrials.gov (NCT06101745), where additional information about the study design and participating centers can be found.
About Curadel Pharma
Boston-based Curadel Pharma specializes in zwitterionic technology applications in medicine. Beyond ZW800-1, the company is developing other innovative products, including CPI-003, a potential best-in-class zwitterionic targeted alpha therapy (TAT) for challenging rare cancers.
The company's platform technology aims to prevent tumor regrowth and resistance while minimizing damage to healthy tissues. This approach represents a novel direction in both surgical imaging and cancer therapeutics, potentially addressing significant unmet needs in multiple medical fields.
