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

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

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.

Study Overview

• Status: Completed
• Conditions: Ureter Injury
• Intervention / Treatment: Drug: IS-001; Drug: No treatment

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. 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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Hospital
  • Texas
    • Austin, Texas, United States, 78758
      • St.David's Medical Center
    • El Paso, Texas, United States, 79902
      • Las Palmas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female subject is between the ages of 18 and 75, inclusive
2. Subject is scheduled to undergo robotic gynecological surgery using a da Vinci® surgical system with Firefly® fluorescent imaging
3. Subject is willing and able to provide informed consent
4. Subject is considered capable of complying with study procedures

Exclusion Criteria:

1. Subject is pregnant or nursing
2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalation; 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; intravenous injection of IS-001 investigational drug
Experimental: Optimal dose-characterization; 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; intravenous injection of IS-001 investigational drug; Drug: No treatment; no drug injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Intuitive Surgical
• Investigators: Principal Investigator: Richard Farnam, MD, Las Palmas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: minimally invasive surgery; robotic-assisted surgery
• Other Study ID Numbers: ISI-124804-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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