A Safety and Efficacy Study of IS-001 Injection in Patients Undergoing Robotic Hysterectomy

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. Stage A of the study will determine the safe optimal dose and Stage B will determine expanded safety and efficacy for intraoperative ureter structure delineation for the identified optimal dose in study participants.

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. Stage A will be a dose-escalation to determine the optimal dose for ureter visualization and Stage B will be an expanded safety and efficacy evaluation of the optimal dose. Stage B will include a no-drug safety control to evaluate the effects of surgery alone on the safety parameters of the study.

Official Title
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A Phase 2 Multi-Center Safety and Efficacy Study of IS-001 Injection in Patients Undergoing Robotic 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
* Drug: No treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subject is between the ages of 18 and 75, inclusive Subject is scheduled to undergo robotic gynecological surgery using a da Vinci® surgical system with Firefly® fluorescent imaging Subject is willing and able to provide informed consent Subject is considered capable of complying with study procedures Exclusion Criteria: Subject is pregnant or nursing Subject has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 4. Subject is already enrolled in another investigational study 5. 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

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Stage A is a dose-cohort escalation to determine optimal efficacious dose, Stage B is an expanded safety and efficacy evaluation of the optimal dose with a no-drug safety control group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation<br>Dose-cohort escalation of single intravenous injection of IS-001 starting with 20 mg (n=8), escalating in 20 mg increments until optimal dose is determined. | Drug: IS-001<br>* intravenous injection of IS-001 investigational drug<br>|
| Experimental: Optimal dose-characterization<br>Single intravenous injection of IS-001 at the optimal dose will be administered to subjects assigned to the treatment group. Safety control subjects will not receive any study drug but will undergo robotic surgery and all associated safety assessment clinical trial procedures. | Drug: IS-001<br>* intravenous injection of IS-001 investigational drug<br>Drug: No treatment<br>* no drug injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 10 minutes | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 30 minutes | 
| Evaluate fluorescent intensity of ureter by signal to background analysis | Fluorescent intensity of ureter evaluated as signal to background | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety 12-Lead EKG Change from Baseline | 12-Lead EKG change from baseline in QTc | 6 hours | 
| Incidence of abnormal blood work in tests results | Safety hematology complete blood count laboratory assessments Change from Baseline | 24 hours | 
| Incidence of abnormal blood work in tests results | Safety hematology complete blood count laboratory assessments Change from Baseline | 14 days | 
| Incidence of abnormal blood work in tests results | Safety hematology comprehensive metabolic panel laboratory assessments Change from Baseline | 24 hours | 
| Incidence of abnormal blood work in tests results | Safety hematology comprehensive metabolic panel laboratory assessments Change from Baseline | 14 days | 
| Incidence of abnormal urinalysis results | Routine urinalysis laboratory assessment change from baseline | 14 days | 
| Safety Adverse Events Monitoring | Drug related adverse events monitoring through 14-days | 14 days | 
| Pharmacokinetics Maximal Concentration (Cmax) of Drug Plasma Levels | Maximal concentration of investigational drug-plasma levels (Cmax) | 0, 1-2 hours and 2-3 hours | 
| Pharmacokinetics Area Under the Plasma Concentration Curve from Time Zero to Last Sampling (AUClast) | Area under the plasma curve from t(0) to last plasma sample | 0, 1-2 hours and 2-3 hours | 
| Pharmacokinetics Area Under the Plasma Concentration Curve from Time Zero Extrapolated to Infinity (AUCinf) | Area under the plasma curve from t(0) extrapolated to infinity | 0, 1-2 hours and 2-3 hours | 
| Pharmacokinetics Drug Plasma Clearance (CL) | Clearance of the investigational drug from plasma | 0, 1-2 hours and 2-3 hours | 
| Pharmacokinetics Terminal Elimination Half-life (t1/2) | Half-life of the investigational drug in plasma | 0, 1-2 hours and 2-3 hours | 
| Pharmacokinetics Apparent Volume of Distribution (Vz) | The apparent volume of distribution of the investigational drug | 0, 1-2 hours and 2-3 hours | 
| Ureter Identification Efficacy on a Nominal Scale | 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 nominal scale where 0=No and 1=Yes | 10 minutes | 
| Ureter Identification Efficacy on a Nominal Scale | 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 nominal scale where 0=No and 1=Yes | 30 minutes | 
| Ureter Identification Efficacy on a Nominal Scale | 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 nominal scale where 0=No and 1=Yes. | 60 minutes | 
| Ureter Delineation Efficacy as Length of Line Drawn in Millimeters | 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 | 
| 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 | 
| 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. | 60 minutes | 
| Surgeon Confidence of Ureter Visibility Assessed Post-Dose by Three-point Likert-type Scale | Intra-operative surgeon rating of ureter visibility in surgical field in both Firefly® and standard white light comparator mode on a three point Likert-type scale where 0=No, 1=Uncertain and 2=Yes. Surgeon ureter visibility score will be compared between the two imaging conditions. | 10 minutes post-dose | 
| Surgeon Confidence of Ureter Visibility Assessed Post-Dose by Three-point Likert-type Scale | Intra-operative surgeon rating of ureter visibility in surgical field in both Firefly® and standard white light comparator mode on a three point Likert-type scale where 0=No, 1=Uncertain and 2=Yes. Surgeon ureter visibility score will be compared between the two imaging conditions. | 30 minutes post-dose | 
| Surgeon Confidence of Ureter Visibility Assessed Post-Dose by Three-point Likert-type Scale | Intra-operative surgeon rating of ureter visibility in surgical field in both Firefly® and standard white light comparator mode on a three point Likert-type scale where 0=No, 1=Uncertain and 2=Yes. Surgeon ureter visibility score will be compared between the two imaging conditions. | 60 minutes post-dose | 
| Surgeon Assessment of Relative Ureter Contrast Post-Dose on a Five-point Likert-type Scale | Intra-operative surgeon rating of relative ureter contrast in surgical field in Firefly® light mode on a five point Likert-type scale where 0=No Fluorescence, 1=Iso-Fluorescence, 2=Mild Fluorescence, 3= Moderate Fluorescence and 4=Strong Fluorescence. Surgeon contrast score will be compared to contrast scores at other time-points. | 10 minutes post-dose | 
| Surgeon Assessment of Relative Ureter Contrast Post-Dose on a Five-point Likert-type Scale | Intra-operative surgeon rating of relative ureter contrast in surgical field in Firefly® light mode on a five point Likert-type scale where 0=No Fluorescence, 1=Iso-Fluorescence, 2=Mild Fluorescence, 3= Moderate Fluorescence and 4=Strong Fluorescence. Surgeon contrast score will be compared to contrast scores at other time-points | 30 minutes post-dose | 
| Surgeon Assessment of Relative Ureter Contrast Post-Dose on a Five-point Likert-type Scale | Intra-operative surgeon rating of relative ureter contrast in surgical field in Firefly® light mode on a five point Likert-type scale where 0=No Fluorescence, 1=Iso-Fluorescence, 2=Mild Fluorescence, 3= Moderate Fluorescence and 4=Strong Fluorescence. Surgeon contrast score will be compared to contrast scores at other time-points. | 60 minutes post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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robotic-assisted surgery, minimally invasive surgery