Clinical trial NCT05754333: A Study to Find Out if ASP5354 Can Clearly Help Show the Ureter During Surgery
Official title: A Phase 3, Multicenter, Prospective, Randomized, Open-label Study for Intraoperative Ureter(s) Visualization When Using ASP5354 With Near Infrared Fluorescence (NIR-F) Imaging in Participants Undergoing Minimally Invasive and Open Abdominopelvic Surgeries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intraoperative Ureter Visualization
Abdominolpelvic Surgery
Keywords: ASP5354
pudexacianinium chloride
Iatrogenic ureteral injury
Abdominopelvic surgery
Near infrared fluorescence
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2023-03-03
Enrollment: 107
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The ureter is the tube that carries urine from the kidneys to the bladder. It is difficult for surgeons to see the ureter during abdominal surgery. This could lead to injuring the ureter which, although rare, could be serious.

This study is about a potential new medical dye, called ASP5354. This dye is injected into the person at the start of surgery and is detected in the ureter. This is done by an imaging machine which has an option called near infrared fluorescence, or NIR-F. Together they show live images of specific parts of the body. In this study, ASP5354 is used with an imaging machine with a NIR-F option to show live images of the ureter during surgery.

People with kidneys that work properly and those with kidney problems can take part. The main aim of the study is to find out how clearly the ureter can be seen with ASP5354 during surgery in adults whose kidneys work properly or who have mild kidney problems. To do this, the surgeons will inject ASP5354 into the person having surgery. Then, the surgeons will compare images of the ureter with an imaging machine using normal white light and with the NIR-F option. Imaging using normal white light is the standard way surgeons see the ureter during surgery.

People 12 years or older who were going to have certain abdominal surgeries may be able to take part.

Everyone taking part will receive ASP5354 during surgery, but how the imaging is done will depend on which group they are in. Before surgery, the adults taking part whose kidneys work properly or who have mild kidney problems will be assigned into 1 of 2 groups by chance alone. Images of the ureter will be checked in 1 group using normal white light and the other group using normal white light and NIR-F. People 18 years and older with more severe kidney problems and all people under 18 years old will not be assigned to 1 of 2 groups: all images of the ureter will be checked using normal white light and NIR-F.

At the start of surgery, the surgeon will inject ASP5354 into the person having surgery, then will start recording a video. Then, after 30 minutes, the surgeon will record how well the ureter can be seen. This will be done by either using normal white light, or normal white light and NIR-F, depending which group each person having surgery is assigned to. For the group to be checked with normal white light and NIR-F, the surgeon will do this every 30 minutes until the end of surgery. For the group to be checked with normal white light only, the surgeon will only do this after the first 30 minutes.

During the study, people will visit the study hospital 3 times. The first visit is to check if they can take part in the study. People will be asked about their medical history, have a medical examination, and their vital signs checked (blood pressure and pulse rate). Also, they will have some blood and urine tests. For women and girls this may include a pregnancy test. People will have their surgery at the second visit. This will be within 28 days of their first visit. This includes having some blood and urine tests before, during, and after surgery. Also, they will have a medical examination, an electrocardiogram (ECG) to check their heart rhythm, and have their vital signs checked. After surgery, people will return to the clinic 15 days later for a final check-up. They will be asked if they have had any medical problems. Also, they will have a medical examination, have their vital signs checked, and have some blood and urine tests.


Eligibility criteria: Inclusion Criteria:

* Participant is scheduled to undergo minimally invasive or open abdominopelvic surgery that may require ureter(s) identification.
* Participant has normal renal function or has varying degrees of chronic kidney disease as defined by the National Kidney Foundation and calculated by individual eGFR using the modification of diet in renal disease (MDRD) formula for adults or the Schwartz formula for adolescents at the screening visit.

  * Adult normal/mild eGFR cohort: eGFR ≥ 60 mL/min
  * Adult moderate/severe eGFR cohort: eGFR ≥ 15 to \< 60 mL/min
  * Adolescent cohort: eGFR ≥ 60 mL/min
* Female participant is not pregnant and at least 1 of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP).
  * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after study intervention administration.
* Female participant must agree not to breastfeed starting at the administration of ASP5354 through 30 days after ASP5354 administration.
* Female participant must not donate ova starting at the administration of ASP5354 through 30 days after ASP5354 administration.
* Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception through at least 30 days after ASP5354 administration.
* Male participant must not donate sperm starting at the administration of ASP5354 through 30 days after ASP5354 administration.
* Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy from the start of ASP5354 administration through 30 days after ASP5354 administration.
* Participant (and/or participant's parent or legal guardian) agrees not to participate in another interventional study involving unapproved study medication while participating in the present study.

Exclusion Criteria:

* Participant has any physical or psychiatric condition which makes the participant unsuitable for study participation.
* Participant is anticipated to require ureteral stenting during surgery.
* Participant has an active urinary tract infection requiring antibiotic therapy.
* Participant has moderate to severe cardiac disease that limits daily functioning (New York Heart Association Class III to IV) or other medical conditions that would impact safety or study compliance.
* Participant has any clinically relevant laboratory abnormality that could contraindicate surgery.
* Participant with body weight \< 30 kilogram (kg).
* Participant has a known or suspected hypersensitivity to ASP5354, indocyanine green (ICG) or any components of the formulation used.
* Participant has had previous exposure to ASP5354.
* Participant has been administered ICG or other near-infrared fluorescent (NIR-F) imaging agents within 48 hours prior to ASP5354 administration, with the exception of participants who receive ICG for lymphatic mapping before the surgery.
* Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to randomization.
* Participant is on hemodialysis, hemodiafiltration or peritoneal dialysis

Primary outcomes:
measure: Intra-participant difference in ureter conspicuity for white light (WL) versus near-infrared fluorescence (NIR-F) for adults with normal renal function or mild renal impairment
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
Secondary outcomes:
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for adults with normal renal function or mild renal impairment
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for adults with normal renal function or mild renal impairment
timeFrame: Up to end of surgery (Day1)
measure: Quantification of ureter conspicuity for WL and NIR-F illumination modes for all participants
timeFrame: Up to end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adolescents
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for adolescents
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for adolescents
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with moderate or severe renal impairment
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for adults with moderate or severe renal impairment
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for adults with moderate or severe renal impairment
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for all participants
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for all participants
timeFrame: Up to end of surgery (Day1)
measure: Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for all participants
timeFrame: Up to end of surgery (Day1)
measure: Number of participants with an average index ureter conspicuity over all NIR-F time points at least 1 point higher than the average index ureter conspicuity over all WL time points
timeFrame: Up to the end of surgery (Day 1)
measure: Percentage of participants with an average index ureter conspicuity over all NIR-F time points at least 1 point higher than the average index ureter conspicuity over all WL time points
timeFrame: Up to the end of surgery (Day 1)
measure: Number of participants with an average index ureter conspicuity over all NIR-F time points at least 2, 3 or 4 points higher than the average index ureter conspicuity over all WL time points
timeFrame: Up to the end of surgery (Day 1)
measure: Percentage of participants with an average index ureter conspicuity over all NIR-F time points at least 2, 3 or 4 points higher than the average index ureter conspicuity over all WL time points
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with normal renal function or mild renal impairment (BICR)
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Intra-participant comparison of ureter conspicuity scores for the WL versus the average of all NIR-F time points for adults with normal renal function or mild renal impairment (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant comparison of ureter conspicuity scores for the WL versus the end of surgery time point score with NIR-F for adults with normal renal function or mild renal impairment (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adolescents (BICR)
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Ureter conspicuity scores for the WL versus the average of all NIR-F time points for adolescents (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Ureter conspicuity scores for the WL versus the end of surgery time point score with NIR F for adolescents (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with moderate or severe renal impairment (BICR)
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Ureter conspicuity scores for the WL versus the average of all NIR-F time points for adults with moderate or severe renal impairment (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Ureter conspicuity scores for the WL versus the end of surgery time point score with NIR F for adults with moderate or severe renal impairment (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for participants in all cohorts (BICR)
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Ureter conspicuity scores for the WL versus the average of all NIR-F time points for participants in all cohorts (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Ureter conspicuity scores for the WL versus the end of surgery time point score with NIR F for participants in all cohorts (BICR)
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with normal renal function or mild renal impairment (by each BICR reader)
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Concordance correlation coefficient (CCC), the inter-rater reliability between the investigators and BICR for the WL versus NIR-F for adults with normal renal function or mild renal impairment
timeFrame: Up to 45 minutes after ASP5354 administration (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus average of all NIR-F for adults with normal renal function or mild renal impairment (by each BICR reader)
timeFrame: Up to the end of surgery (Day 1)
measure: CCC, the inter-rater reliability between the investigators and BICR for the WL versus the average of all NIR-F time points for adults with normal renal function or mild renal impairment
timeFrame: Up to the end of surgery (Day 1)
measure: Intra-participant difference in ureter conspicuity for WL versus the end of surgery with NIR-F for adults with normal renal function or mild renal impairment (by each BICR reader)
timeFrame: Up to the end of surgery (Day 1)
measure: CCC, the inter-rater reliability between the investigators and BICR for the WL versus the end of surgery time point score with NIR-F for adults with normal renal function or mild renal impairment
timeFrame: Up to the end of surgery (Day 1)
measure: Number of participants with Treatment-emergent adverse events (TEAEs)
timeFrame: Up to Day 25
measure: Number of participants with serious TEAEs
timeFrame: Up to Day 25
measure: Number of participants with laboratory value abnormalities and/or adverse events (AEs)
timeFrame: Up to Day 25
measure: Number of participants with vital sign abnormalities and/or adverse events (AEs)
timeFrame: Up to Day 25
measure: Number of participants with electrocardiogram (ECG) /cardiac monitoring abnormalities and/or adverse events (AEs)
timeFrame: Up to Day 2
measure: Pharmacokinetics (PK) of ASP5354 in plasma:concentration
timeFrame: Up to 2 hours post-surgery (Day 1)
measure: PK of ASP5354 in urine:concentration
timeFrame: Up to end of surgery (Day 1)
measure: PK of ASP5354 in urine: amount of ASP5354 excreted in urine (Ae)
timeFrame: Up to end of surgery (Day 1)
measure: PK of ASP5354 in urine: percentage of ASP5354 dose excreted into urine (Ae percentage)
timeFrame: Up to end of surgery (Day 1)
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Tampa
country: United States
facility: Advent Health Tampa
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: