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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Ureter Injury

Intervention / Treatment
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* Drug: IS-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria Female subject is between the ages of 18 and 75, inclusive. Subject is scheduled to undergo robotic-assisted gynecological procedure using a da Vinci® surgical system with Firefly® fluorescent imaging. Subject is willing and able to provide informed consent. Exclusion Criteria: Subject is pregnant or nursing. Subject has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subject is already enrolled in another investigational drug or device study receiving therapeutic agents within the past 6 months 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. Subject has a known or suspected hypersensitivity to indocyanine green (ICG) Subject has any of the following screening laboratory values: Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT) ≥ 2.5 × upper limit normal (ULN) Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) ≥ 2.5 × upper limit normal (ULN).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Efficacy<br>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<br>* IV injection of IS-001 drug substance with near infrared (NIR) imaging<br>|

What is the study measuring?
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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 |