A Safety and Feasibility Study of IS-001 Injection in Patients Undergoing Robotic Colorectal Surgery

Study Overview
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Brief Summary
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This study evaluates the safety and feasibility 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 feasibility 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 2 Multi-Center Safety and Feasibility Study of IS-001 Injection in Patients Undergoing Robotic-Assisted Colorectal 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: Male and female subjects between the ages of 18 and 75, inclusive Subject is scheduled to undergo robotic-assisted rectal, sigmoid, or left colon resection surgery using the da Vinci® X/Xi Surgical System with Firefly® Fluorescent Imaging Exclusion Criteria: Subject is pregnant or nursing Subject has known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Subject has any of the following screening laboratory values: eGFR < 60 mL/min/1.73 m^2 Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase ≥ 2.5 × ULN Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase ≥ 2.5 × ULN 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 Subjects with known or suspected hypersensitivity to indocyanine green (ICG) or any components of the formulation used.

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

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Single Arm<br>Single Arm Safety and Feasibility Study of IS-001 with 20 mg in Multiple Injections | Drug: IS-001<br>* Intravenous injection of IS-001 investigational drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 10 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 30 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 45 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 10 minutes after second IS-001 injection during surgery | 
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 30 minutes after second IS-001 injection during surgery | 
| Evaluate ureter visualization by Independent Reader | Independent reader assessment of ureter visibility of a 5 second video segment of the surgical field in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 45 minutes after second IS-001 injection during surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 10 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 30 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 45 minutes after first IS-001 injection during surgery | 
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 10 minutes after second IS-001 injection during surgery | 
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 30 minutes after second IS-001 injection during surgery | 
| Evaluate ureter visualization by Intra-operative surgeon | Intra-operative surgeon assessment of ureter visibility in both Firefly® and standard white light comparator mode on a Five-point rating scale where 1 = Not Visible, 1 = Questionably Visible, 3 = Low Visibility, 4 = Visible, 5 = Clearly Visible | 45 minutes after second IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 10 minutes after first IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 30 minutes after first IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 45 minutes after first IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 10 minutes after second IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 30 minutes after second IS-001 injection during surgery | 
| Ureter Delineation Efficacy as Length of Line Drawn | Independent reader assessment of ureter delineation on a still frame of the surgical field in both Firefly® and standard white light comparator mode. Length of line drawn on still frame where ureter is visible to independent reader is compared between imaging conditions. | 45 minutes after second IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 10 minutes after first IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 30 minutes after first IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 45 minutes after first IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 10 minutes after second IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 30 minutes after second IS-001 injection during surgery | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 45 minutes after second IS-001 injection during surgery | 
| Safety 12-Lead EKG Change from Baseline | 12-Lead EKG change from baseline in QTc | 6 hours after first IS-001 injection post surgery | 
| Incidence of abnormal blood work in tests results | Safety hematology complete blood count laboratory assessments Change from Baseline | Before same-day discharge or 24 hours after first IS-001 injection post surgery | 
| Incidence of abnormal blood work in tests results | Safety hematology comprehensive metabolic panel laboratory assessments Change from Baseline | Before same-day discharge or 24 hours after first IS-001 injection post surgery | 
| Incidence of abnormal blood work in tests results | Safety hematology complete blood count laboratory assessments Change from Baseline | 14 days post surgery | 
| Incidence of abnormal blood work in tests results | Safety hematology comprehensive metabolic panel laboratory assessments Change from Baseline | 14 days post surgery | 
| Incidence of abnormal urinalysis results | Routine urinalysis laboratory assessment change from baseline | 14 days post surgery | 
| Safety Adverse Events Monitoring | Drug related adverse events monitoring through 14-days | 14 days post surgery |