Primary objective:- To assess the feasibility of a single intravenous injection of OTL38 in detecting endometriosis during surgery by determining the concordance between fluorescent signal and histopathological confirmed endometriotic tissue.- To…
ID
Source
Brief title
Condition
- Obstetric and gynaecological therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
- To determine the sensitivity or true positive rate (TPR) for OTL38 in
combination with NIR fluorescence imaging, defined as the proportion of
fluorescent positive tissue samples (of resected tissue or biopsies) that are
histologically confirmed endometriotic tissue and FR+ relative to the total
number of tissue samples confirmed to be FR+ and endometriotic tissue.
Sensitivity = (True Positive)/(True Positive +False Negative).
- False positive rate (FPR) for OTL38 in combination with fluorescent light,
for the purpose of this protocol, will be calculated as 1 * the Positive
Predictive Value (PPV) and is defined as the proportion of fluorescent positive
tissue samples removed (of resected tissue or biopsies) that are histologically
confirmed to be non-endometriotic tissue by the pathologist relative to the
total number of tissue samples removed with fluorescent light imaging. False
Positive Rate = (False Positives) / (True Positives + False Positives).
- Incidence rates of all treatment-emergent AEs (TEAEs), adverse device effects
(ADEs), and SAEs, from the time of OTL38 administration until follow-up visit
3.
Secondary outcome
Secondary endpoint:
- The proportion of lesions identification with OTL-38 and NIR that could not
otherwise be identified by white light and finger palpation.
Background summary
Endometriosis is affecting millions of reproductive-aged women worldwide and is
associated with substantial morbidity, including pelvic pain, multiple
operations, and infertility. The mainstay of diagnosis has been visualisation
of lesions by laparoscopy or laparotomy. Surgery is also the preferred method
of treatment for severe endometriosis aiming for removal of as many lesions as
possible. The diagnosis of peritoneal endometriosis may be difficult due to the
polymorphic aspects of the lesions. Enhanced intraoperative detection of
endometriosis lesions with fluorescence imaging has the potential to provide
better identification and radical resection of peritoneal endometriosis.
Folate receptor * (FR*) is expressed on endometriotic tissue and OTL0038, a
folate analog ligand conjugated to an indole cyanine like green dye developed
as an imaging agent for patients with tumors or benign tissue that overexpress
FR*, could be suitable for targeted intraoperative imaging of endometriosis.
Study objective
Primary objective:
- To assess the feasibility of a single intravenous injection of OTL38 in
detecting endometriosis during surgery by determining the concordance between
fluorescent signal and histopathological confirmed endometriotic tissue.
- To assess the safety and tolerability of single intravenous dose of OTL38.
Secondary objective:
- Localization of occult endometriotic lesions with NIR imaging and OTL38, that
would otherwise remain invisible with white light only.
Study design
* This is a phase 2, single-center, single dose, open-label pilot study in
endometriosis patients scheduled to undergo surgery.
* Each patient will be dosed with 0.025 mg/kg OTL38 intravenously.
Intervention
* Infusion of OTL38 0.025 mg/kg.
Study burden and risks
Risks:
Hypersensitivity reactions
Risks of taking blood samples: pain, bruising, infection
Presence of a camera system in the operating room
Burden:
Extra time investment
The risks of participation for the subjects in the trial include
hypersensitivity reactions. These risks are deemed minimal.
Nevertheless precautionary measures (supervised administration by qualified
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. We therefore believe this research that, could possibly provide a
useful tool to increase detection of endometriosis spots.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1. Female (premenopausal) patients 18 years of age and older
2. Patients scheduled for elective surgery (laparoscopic or laparotomy) for the
diagnosis or treatment of endometriosis
3. WHO performance score of 0-2
4. A negative serum pregnancy test at screening followed by a negative serum
pregnancy test on the day of surgery or day of admission for female patients of
childbearing potential
5. Female patients of childbearing potential agree to use an acceptable form of
contraception from the time of signing informed consent until 90 days after
study completion
6. Ability to understand the requirements of the study, provide written
informed consent and authorization of use and disclosure of protected health
information, and agree to abide by the study restrictions
Exclusion criteria
1. Previous exposure to OTL38
2. Any medical condition that in the opinion of the investigators could
potentially jeopardize the safety of the patient
3. History of anaphylactic reactions
4. History of allergy to any of the components of OTL38, including folic acid
5. Pregnancy (or positive pregnancy test) or breast-feeding
6. Presence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule
7. Impaired renal function defined as eGFR< 50 mL/min/1.73m2
8. Impaired liver function defined as values > 3x the upper limit of normal
(ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST),
alkaline phosphatase (ALP), or total bilirubin
9. Received an investigational agent in another investigational drug or vaccine
trial within 30 days prior to surgery
10. Known sensitivity to fluorescent light
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003693-27-NL |
| CCMO | NL67992.056.18 |
| Other | Trial NL7607 |