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

Phase 2
Completed
Conditions
Ureter Injury
Interventions
Registration Number
NCT03937505
Lead Sponsor
Intuitive Surgical
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
94
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

  3. 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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Optimal dose-characterizationNo treatmentSingle 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.
Dose-escalationIS-001Dose-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.
Optimal dose-characterizationIS-001Single 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.
Primary Outcome Measures
NameTimeMethod
Evaluate fluorescent intensity of ureter by signal to background analysis60 minutes

Fluorescent intensity of ureter evaluated as signal to background

Secondary Outcome Measures
NameTimeMethod
Incidence of abnormal blood work in tests results14 days

Safety hematology comprehensive metabolic panel laboratory assessments Change from Baseline

Pharmacokinetics Maximal Concentration (Cmax) of Drug Plasma Levels0, 1-2 hours and 2-3 hours

Maximal concentration of investigational drug-plasma levels (Cmax)

Pharmacokinetics Apparent Volume of Distribution (Vz)0, 1-2 hours and 2-3 hours

The apparent volume of distribution of the investigational drug

Ureter Identification Efficacy on a Nominal Scale60 minutes

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.

Safety 12-Lead EKG Change from Baseline6 hours

12-Lead EKG change from baseline in QTc

Pharmacokinetics Area Under the Plasma Concentration Curve from Time Zero Extrapolated to Infinity (AUCinf)0, 1-2 hours and 2-3 hours

Area under the plasma curve from t(0) extrapolated to infinity

Pharmacokinetics Terminal Elimination Half-life (t1/2)0, 1-2 hours and 2-3 hours

Half-life of the investigational drug in plasma

Ureter Delineation Efficacy as Length of Line Drawn60 minutes

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.

Safety Adverse Events Monitoring14 days

Drug related adverse events monitoring through 14-days

Pharmacokinetics Area Under the Plasma Concentration Curve from Time Zero to Last Sampling (AUClast)0, 1-2 hours and 2-3 hours

Area under the plasma curve from t(0) to last plasma sample

Pharmacokinetics Drug Plasma Clearance (CL)0, 1-2 hours and 2-3 hours

Clearance of the investigational drug from plasma

Incidence of abnormal urinalysis results14 days

Routine urinalysis laboratory assessment change from baseline

Ureter Delineation Efficacy as Length of Line Drawn in Millimeters10 minutes

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.

Surgeon Confidence of Ureter Visibility Assessed Post-Dose by Three-point Likert-type Scale60 minutes post-dose

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.

Surgeon Assessment of Relative Ureter Contrast Post-Dose on a Five-point Likert-type Scale60 minutes post-dose

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.

Trial Locations

Locations (3)

George Washington University Hospital

🇺🇸

Washington, District of Columbia, United States

St.David's Medical Center

🇺🇸

Austin, Texas, United States

Las Palmas Medical Center

🇺🇸

El Paso, Texas, United States

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