A Study to Find Out if ASP5354 Can Clearly Help Show the Ureter During Surgery

Study Overview
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Brief Summary
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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 10 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.

Official Title
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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

Conditions
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Intraoperative Ureter Visualization, Abdominolpelvic Surgery

Intervention / Treatment
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* Drug: pudexacianinium chloride


Participation Criteria
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Eligibility Criteria
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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 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 screening. Participant is on hemodialysis, hemodiafiltration or peritoneal dialysis

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: White Light/near-infrared fluorescence - Adults with normal renal function or mild renal impairment<br>Adult participants with normal renal function or mild renal impairment will receive a single dose of ASP5354. | Drug: pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: White Light - Adults with normal renal function or mild renal impairment<br>Adult participants with normal renal function or mild renal impairment will receive a single dose of ASP5354. | Drug: pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: White Light/near-infrared fluorescence - Adolescents<br>Adolescent participants will receive a single dose of ASP5354. | Drug: pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: White Light/near-infrared fluorescence - Adults with moderate or severe renal impairment<br>Adult participants with moderate or severe renal impairment will receive a single dose of ASP5354. | Drug: pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| 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 | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Quantification of ureter conspicuity for WL and NIR-F illumination modes for all participants | Ureter conspicuity will be quantified by image analysis measuring the color contrast when ASP5354 is present in the ureter. | Up to end of surgery (Day 1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for adolescents | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for adolescents | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for adolescents | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with moderate or severe renal impairment | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| 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 | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| 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 | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for all participants | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Intra-participant comparison of ureter conspicuity scores for WL versus the average of all NIR-F time points for all participants | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Intra-participant comparison of ureter conspicuity scores for WL versus the end of surgery score with NIR-F for all participants | Conspicuity will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to end of surgery (Day1) | 
| Number of participants with Treatment-emergent adverse events (TEAEs) | Adverse events (AEs) will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A TEAE is defined as an AE observed after administration of the study intervention and up to the follow-up period. | Up to Day 15 | 
| Number of participants with serious TEAEs | A Serious Adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important event. A serious TEAE is defined as an SAE observed after administration of the study intervention and up to the follow-up period. | Up to Day 15 | 
| Number of participants with laboratory value abnormalities and/or adverse events (AEs) | Number of participants with potentially clinically significant laboratory values | Up to Day 15 | 
| Number of participants with vital sign abnormalities and/or adverse events (AEs) | Number of participants potentially clinically significant vital signs | Up to Day 15 | 
| Number of participants with electrocardiogram (ECG) /cardiac monitoring abnormalities and/or adverse events (AEs) | Number of participants potentially clinically significant ECGs/cardiac monitoring | Up to 2 hours post-surgery (Day 1) | 
| Pharmacokinetics (PK) of ASP5354 in plasma:concentration | Concentration will be recorded from the PK plasma samples collected | Up to 2 hours post-surgery (Day 1) | 
| PK of ASP5354 in urine:concentration | Concentration will be recorded from the PK urine samples collected | Up to end of surgery (Day 1) | 
| PK of ASP5354 in urine: amount of ASP5354 excreted in urine (Ae) | Ae will be recorded from the PK urine samples collected | Up to end of surgery (Day 1) | 
| PK of ASP5354 in urine: percentage of ASP5354 dose excreted into urine (Ae percentage) | Ae percentage will be recorded from the PK urine samples collected | Up to end of surgery (Day 1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with normal renal function or mild renal impairment (BICR) | BICR's (blinded independent central review) conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| 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) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| 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) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for adolescents (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Ureter conspicuity scores for the WL versus the average of all NIR-F time points for adolescents (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Ureter conspicuity scores for the WL versus the end of surgery time point score with NIR F for adolescents (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for adults with moderate or severe renal impairment (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Ureter conspicuity scores for the WL versus the average of all NIR-F time points for adults with moderate or severe renal impairment (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| 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) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Intra-participant difference in ureter conspicuity for WL versus NIR-F for participants in all cohorts (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Ureter conspicuity scores for the WL versus the average of all NIR-F time points for participants in all cohorts (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Ureter conspicuity scores for the WL versus the end of surgery time point score with NIR F for participants in all cohorts (BICR) | BICR's conspicuity assessment of the ureter will be scored individually for each illumination mode using a 5-Point Likert Scale, ranging from 1 (None) to 5 (Excellent) | Up to the end of surgery (Day 1) | 
| Inter-rater reliability between the surgeons and BICR for the WL versus NIR-F for adults with normal renal function or mild renal impairment | Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment | Up to 45 minutes after ASP5354 administration (Day 1) | 
| Inter-rater reliability between the surgeons and BICR for the WL versus the average of all NIR-F time points for adults with normal renal function or mild renal impairment | Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment | Up to the end of surgery (Day 1) | 
| Inter-rater reliability between the surgeons 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 | Determine degree of concordance between intra-operative ureter visualization assessment and independent reader ureter visualization assessment | Up to the end of surgery (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP5354, pudexacianinium chloride, Iatrogenic ureteral injury, Abdominopelvic surgery, Near infrared fluorescence