Primary objectives: To assess the feasibility of ZW800-1 in intraoperative detection of the urinary tract using the NIR fluorescence imaging system. Secondary objectives: To define the optimal dose of ZW800-1 for intraoperative imaging of the…
ID
Source
Brief title
Condition
- Urinary tract signs and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy endpoint: Signal-to-background ratio, defined as fluorescence signal
in the ureters compared to fluorescence signal of the surrounding tissue, at
different doses.
Secondary outcome
Safety and tolerability endpoint: The occurrence or absence of adverse events
following administration of ZW800-1 in patients.
Pharmacokinetic endpoint: Analysis of blood and urine samples for serum
biochemistry, hematology and pharmacokinetics.
Background summary
Iatrogenic ureteral injury during abdominal surgery is a rare but serious
complication with incidences varying from 0.7% to 10%.(1) When this
complication is detected during surgery, the damage can often be repaired.
However, most injuries remain unnoticed, resulting in severe long-term
complications such as urogenital fistula or kidney failure. About 44% of all
cases with iatrogenic ureteral injuries occur in patients with malignancies.
Important risk factors include, previous surgery in the pelvic area, obesity
and previous radiotherapy in the pelvic area. A preventive measure is inserting
a double J catheter, which can be palpated during surgery to identify the
ureters. However this method has its disadvantages, as it may injure or infect
the ureter and most importantly it cannot be used during laparoscopic surgery.
Over the last years, near-infrared fluorescence imaging has emerged to empower
surgeons to identify anatomical structures in real-time during surgery.
Fluorescence imaging using near-infrared (NIR) light (700-900 nm) can assist
surgeons in recognizing structures that need to be spared, such as blood
vessels and ureters, and structures that need to be resected, such as
tumors(2). These imaging systems work with an external light source with a
defined wavelength (700-900 nm) to illuminate the injected fluorescent agent.
As the light travels through the tissue, it excites the fluorescent agent and
releases light which is subsequently detected by the NIR imaging system,
permitting high sensitivity detection of a desired target within the surgical
field. Currently, the only clinically available NIR fluorophores are methylene
blue, 5-ALA, and indocyanine green (ICG), but these fluorophores cannot easily
be conjugated covalently to other molecules. Moreover, the fluorescence
emission intensity and clearance routes are far from optimal. New fluorophores
are needed with improved optical qualities and in vivo properties.
ZW800-1 is a novel fluorophore engineered with geometrically balanced, net
neutral polyionicity. In pre-clinical studies it has proven to be a valid agent
for molecular imaging, due to low non-specific binding and uptake, and an
exclusive renal clearance, permitting imaging of the gastrointestinal tract. In
rat studies, the ureters became fluorescent for several hours after a low dose
of ZW800-1. More importantly, ZW800-1 has been proven safe. The safety,
tolerability and pharmacokinetics have been studied in a phase 1 study in 16
healthy volunteers, without signs of safety concern. Based on the
characteristics, safety and distinctive pharmacokinetics we believe that
ZW800-1 is an ideal candidate to visualize the urinary tract during surgery to
prevent iatrogenic ureteral damage. The NIR fluorescence signal of ZW800-1 can
penetrate through 5-10 mm of tissue and is invisible to the naked eye.
Study objective
Primary objectives: To assess the feasibility of ZW800-1 in intraoperative
detection of the urinary tract using the NIR fluorescence imaging system.
Secondary objectives: To define the optimal dose of ZW800-1 for intraoperative
imaging of the urinary tract.
Study design
The study is an open-label, single ascending dose, exploratory study,
consisting of 12 patients undergoing laparoscopic abdominal surgery. The study
will consist of 3 cohorts where 3 different doses of ZW800-1 will be explored
to select the optimal dose for surgery. The selected doses are based on the
pre-clinical and phase I results. ZW800-1 will be administered in a bolus
injection during surgery after exposure of the ureters. Patients will be under
anesthesia during administration.
* Cohort 1 (up to 4 patients): 2.5 mg ZW800-1
* Cohort 2 (up to 4 patients): 5 mg ZW800-1
* Cohort 3 (up to 4 patients): 10 mg ZW800-1 / 1 mg ZW800-1 / repeated dose of
2.5 mg ZW800-1
Study burden and risks
The risks of participation for the patients in the trial include
hypersensitivity reactions. These risks are deemed minimal. Nevertheless
precautionary measures (supervised administration by qualifìed staff and
availability of medical treatment to treat hypersensitivity reactions) are in
place and these effects are generally well manageable. The burden of the trial
is minimal, the research will for the largest part coincide with routine care
and the proposed procedures are minimally invasive. This research could
possibly provide a useful tool to enhance visualization of ureters and, hence,
reducing the risk of ureteral damage. We believe therefore that this study is
justified.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1) Patients 18 years or older;;2) Patients scheduled and eligible for laparoscopic surgery in the lower abdominal or pelvic area; ;3) Patients should be capable and willing to give informed consent before study specific procedures;;4) No unacceptable known cardiovascular or pulmonary disease, renal or liver dysfunction;;5) The screening ECG and laboratory test results are within normal limits, or if any are outside of normal limits they are considered to be clinically insignificant;;6) Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Exclusion criteria
1) History of a clinically significant allergy;;2) Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential;;3) Any condition that the investigator considers to be potentially jeopardizing the patients well-being or the study objectives.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001954-32-NL |
| CCMO | NL61892.058.17 |