IS-001 Injection in Patients Undergoing Robotic-Assisted Gynecological Surgery

A Phase 3 Multi-Center Efficacy Study of IS-001 Injection in Patients Undergoing Robotic-Assisted Gynecological Surgery Using the da Vinci® Surgical System With Firefly® Fluorescent Imaging

This study evaluates the safety and efficacy of intravenous injection of IS-001 to aid in intraoperative ureter structure delineation.

Study Overview

• Status: Not yet recruiting
• Conditions: Ureter Injury
• Intervention / Treatment: Drug: IS-001

Detailed Description

Injury to the ureter, the duct by which urine passes from the kidney into the bladder, is a well-known and serious complication of pelvic and abdominal surgery that frequently goes unrecognized intraoperatively. This study seeks to evaluate the safety and efficacy of intravenous IS-001 injection to improve surgeon ureter visualization during robotic-assisted surgery with the da Vinci® Surgical System and Firefly® imaging.

• Study Type: Interventional
• Enrollment (Estimated): 237
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion Criteria

1. Female subject is between the ages of 18 and 75, inclusive.
2. Subject is scheduled to undergo robotic-assisted gynecological procedure using a da Vinci® surgical system with Firefly® fluorescent imaging.
3. Subject is willing and able to provide informed consent.

Exclusion Criteria:

1. Subject is pregnant or nursing.
2. Subject has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
3. Subject is already enrolled in another investigational drug or device study receiving therapeutic agents within the past 6 months
4. Subject has any other condition or personal circumstance that, in the judgment of the Investigator, might interfere with the collection of complete quality data or represents an unacceptable safety profile.
5. Subject has a known or suspected hypersensitivity to indocyanine green (ICG)

6. Subject has any of the following screening laboratory values:

   1. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2
   2. Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT) ≥ 2.5 × upper limit normal (ULN)
   3. Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≥ 2.5 × upper limit normal (ULN).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Efficacy; Single intravenous injection of IS-001 and ureter visualization and delineation will be compared in white light standard of care and near-infrared (NIR) imaging mode.	Drug: IS-001; IV injection of IS-001 drug substance with near infrared (NIR) imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible.	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 10 minutes after IS-001 injection	10 minutes
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 30 minutes after IS-001 injection	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 10 minutes after injection	10
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 30 minutes after injection	30
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 10 minutes after IS-001 injection	10 minutes
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 30 minutes after IS-001 injection	30 minutes
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 45 minutes after IS-001 injection	45 minutes
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 45 minutes after IS-001 injection	45 minutes
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode at 45 minutes after IS-001 injection	45 minutes
Ureter signal-to-background ratio evaluating contrast of fluorescent signal in near infrared imaging mode	Evaluate ureter signal-to-background ratio in Firefly imaging across time points at (a) the pelvic brim location and (b) the uterine arteries location after IS-001 injection.	10 minutes
Ureter signal-to-background ratio evaluating contrast of fluorescent signal in near infrared imaging mode	Evaluate ureter signal-to-background ratio in Firefly imaging across time points at (a) the pelvic brim location and (b) the uterine arteries location after IS-001 injection.	30 minutes
Ureter signal-to-background ratio evaluating contrast of fluorescent signal in near infrared imaging mode	Evaluate ureter signal-to-background ratio in Firefly imaging across time points at (a) the pelvic brim location and (b) the uterine arteries location after IS-001 injection.	45 minutes
concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment	Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment at (a) the pelvic brim location and (b) the uterine arteries location	10 minutes
concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment	Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment at (a) the pelvic brim location and (b) the uterine arteries location	30 minutes
concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment	Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment at (a) the pelvic brim location and (b) the uterine arteries location	45 minutes
Determine degree of concordance of ureter visualization between independent readers	Determine degree of concordance of ureter visualization between independent readers at (a) the pelvic brim location and (b) the uterine arteries location	10 minutes
Determine degree of concordance of ureter visualization between independent readers	Determine degree of concordance of ureter visualization between independent readers at (a) the pelvic brim location and (b) the uterine arteries location	30 minutes
Determine degree of concordance of ureter visualization between independent readers	Determine degree of concordance of ureter visualization between independent readers at (a) the pelvic brim location and (b) the uterine arteries location	45 minutes
degree of concordance of ureter visualization within independent readers	Determine degree of concordance of ureter visualization within independent readers at (a) the pelvic brim location and (b) the uterine arteries location	10 minutes
degree of concordance of ureter visualization within independent readers	Determine degree of concordance of ureter visualization within independent readers at (a) the pelvic brim location and (b) the uterine arteries location	30 minutes
degree of concordance of ureter visualization within independent readers	Determine degree of concordance of ureter visualization within independent readers at (a) the pelvic brim location and (b) the uterine arteries location	45 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible after second injection	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging compared white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	10 minutes
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible after second injection	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging compared white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	30 minutes
Independent reader assessment of ureter visualization by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible after second injection	Evaluate ureter visualization by independent reader at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging compared white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	45 minutes
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length after second injection	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode after second injection for procedures lasting longer than 60 minutes	10 minutes
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length after second injection	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode after second injection for procedures lasting longer than 60 minutes.	30 minutes
Independent reader assessment of ureter length delineation by line drawing on recorded frame measured in arbitrary unit length after second injection	Evaluate ureter length delineation by independent reader at (a) the pelvic brim and (b) uterine arteries location in Firefly® mode compared to white light mode after second injection for procedures lasting longer than 60 minutes.	45 minutes
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible - 2nd injection	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging over white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	10 minutes
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible - 2nd injection	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging over white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	30 minutes
Ureter visualization based on intraoperative surgeon's rating by 1-5 Likert visualization rating scale from 1 not visible, 2 questionably visible, 3 low visibility, 4 visible, 5 clearly visible - 2nd injection	Evaluate ureter visualization based on intraoperative surgeon's rating at (a) the pelvic brim and (b) uterine arteries in Firefly® imaging over white light mode after 2nd IS-001 injection for procedures lasting longer than 60 minutes	45 minutes

Collaborators and Investigators

• Sponsor: Intuitive Surgical

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ISI-124804-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No