A Phase 2/3 trial to investigate visualization of the ureters with nizaracianine triflutate, intravenous, in participants aged 18 years or older, undergoing abdominopelvic surgical procedures [TRIPHASE TRIAL].

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Curadel Surgical Innovations Inc., Curadel Surgical Innovations B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Trial duration

21 May 2024 → ongoing

Decision date (initial)

2023-11-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-503241-63-00

WHO UTN

U1111-1296-0306

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Dose response, Diagnosis

The Phase 2 primary objectives are (1) to assess the safety of nizaracianine, (2) to assess the efficacy of nizaracianine, and (3) to define the near-optimal dose of nizaracianine for enhancing ureter anatomy and function during surgery using NIR fluorescent light.
The Phase 3 primary objectives are (1) to assess the safety of nizaracianine and (2) to assess the efficacy of nizaracianine at its near-optimal dose for enhancing delineation of ureter anatomy (technical benefit) and ureter function (clinical benefit) during surgery using NIR fluorescent light.

Secondary objectives 11

1. i. Determining if nizaracianine reduces invasive procedures and/or dissection of surrounding tissues that would otherwise be required to identify the ureters
2. ii. Determining if nizaracianine reduces the time required for initial ureter identification
3. iii. Determining if nizaracianine permits assessment of ureter integrity (leaks) and ureter function (flow/obstructions) at closing without the need for invasive procedures and/or tissue manipulation
4. iv. Determining if nizaracianine reduces or eliminates the skeletonization/ureter dissection that is now typically employed in some surgical procedures as part of ureter identification
5. v. Estimating the average time period of ureter visualization provided by the first dose of nizaracianine
6. vi. Estimating the average dose interval and average number of doses of nizaracianine preferred by surgeons for optimal visualization of the ureters during surgeries of various lengths (Phase 3 only)
7. vii. Determining if nizaracianine increases the proportion of cases of ureter injury that are detected intraoperatively
8. viii. Determining if nizaracianine assisted ureter repair in cases where ureter injury was detected intraoperatively
9. ix. Determining if nizaracianine reduces the overall length of surgery for a given procedure type (Phase 3A only)
10. Exploratory objectives: i. Determining whether nizaracianine helps identify bladder anatomy in bladder-involved cases
11. Exploratory objectives: ii. Determining whether nizaracianine provides NIR fluorescence enhancement of blood vessels in the surgical field

Conditions and MedDRA coding

Urinary tract imaging

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003367-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 18 years old
2. Scheduled to undergo a medically necessary abdominopelvic surgical procedure expected to last ≥ 2 hours (Phase 2) or any duration (Phase 3), during which one or more ureters should be visualized during the procedure
3. For Phase 2, the procedure must require dissection or mobilization of one or both ureters.
4. The planned surgical procedure is open or MIS (including robotic).
5. Both ureters are expected to be present and functional.
6. Capable and willing to provide informed consent prior to study-specific procedures
7. Screening laboratory test results are within normal limits, or if any are outside of normal limits, they are considered by the site PI, or other medically qualified designee, to be clinically insignificant.
8. Negative pregnancy test in women of childbearing potential

Exclusion criteria 15

1. This Phase 2 only exclusion was removed. Intentionally left blank
2. Known sensitivity to fluorescent light
3. Alcohol or recreational drug use that meets DSM5 criteria for moderate or severe substance use disorder
4. Pregnant or breastfeeding, or lack of effective contraception for at least one week post-surgery in male or female subjects with reproductive potential: for males, condom use; for females, oral contraceptives, diaphragm, or IUDs
5. Any condition that the investigator considers to be potentially jeopardizing to the study subject’s well-being or the study’s objectives.
6. Participated in an interventional clinical research study within the previous 30 days.
7. Known cardiovascular or pulmonary disease, renal or liver dysfunction, immunological disease, diabetes, or active cancer that would render the study subject unfit for surgery
8. The planned surgical procedure is renal transplant or nephrectomy [note: partial nephrectomy is permitted provided that estimated GFR is not expected to fall below normal age-based limits]
9. Prior renal transplant
10. Impaired renal function defined as an eGFR < 50 mL/min/1.73m2
11. Impaired liver function defined as values > 1.5X the ULN for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin, or < LLN for albumin
12. Coagulopathy as manifested by INR > 1.3 (unless patient is on anti-coagulants)
13. Subjects with a marked baseline prolongation of QT/QTc interval (e.g., a QTc interval > 480 msec [CTCAE grade 1] using Fridericia’s QT correction factor
14. History of a clinically significant allergy or anaphylaxis to a component of the IMP
15. The planned use of an 800 nm NIR fluorophore that is not nizaracianine (e.g., indocyanine green or pafolacianine) immediately before, during, or immediately after the planned abdominopelvic procedure.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase 2: Determination of the near-optimal dose in the context of an acceptable safety profile
2. Phase 2 and 3: Safety assessment
3. Phase 2 and 3: The proportion of subjects for whom the surgeon is able to successfully identify the required length of the ureters (specified prior to surgery by the surgeon) with a peak SBR ≥ 1.5

Secondary endpoints 11

1. i. Proportion of cases in which ureter identification did not require invasive procedures or dissection of surrounding tissue
2. ii. Average time required for initial ureter identification (minutes)
3. iii. Proportion of cases for which ureter integrity status (leak vs. no leak) and function (flow/obstructions) were determined at closing without the need for invasive procedures and/or tissue manipulation
4. iv. Among cases that normally require ureter skeletonization/ureter dissection, the proportion of cases where skeletonization/ureter dissection could be reduced or eliminated
5. v. Average time period of ureter visualization provided by the first dose of nizaracianine
6. vi. Average dose interval and average number of doses of nizaracianine preferred by surgeons for optimal visualization of the ureters during surgeries of various lengths (Phase 3 only)
7. vii. Among subjects with ureter injury, the proportion of cases detected intraoperatively
8. viii. Among subjects with intraoperative detection of ureter injury, the proportion of cases in which nizaracianine assisted repair
9. ix. For a particular surgical procedure type, average overall surgery time (Phase 3A only)
10. Exploratory endpoint: i. In bladder-involved cases, the proportion of cases where nizaracianine helped identify bladder anatomy
11. Exlporatory endpoint: ii. The proportion of cases where nizaracianine provided NIR fluorescence enhancement of blood vessels in the surgical field

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Curadel Surgical Innovations Inc.

Sponsor organisation

Curadel Surgical Innovations Inc.

Address

11 Erie Drive

City

Natick

Postcode

01760-1312

Country

United States

Scientific contact point

Organisation

Curadel Surgical Innovations Inc.

Contact name

John V. Frangioni, M.D., Ph.D.

Public contact point

Organisation

Curadel Surgical Innovations Inc.

Contact name

John V. Frangioni, M.D., Ph.D.

Curadel Surgical Innovations B.V.

Sponsor organisation

Curadel Surgical Innovations B.V.

Address

Basisweg 10

City

Amsterdam

Postcode

1043 AP

Country

Netherlands

Public contact point

Organisation

Curadel Surgical Innovations Inc.

Contact name

John V. Frangioni, M.D., Ph.D.

Sponsor responsibilities

Article 77 compliance

Curadel Surgical Innovations Inc.

Contact point sponsor

Curadel Surgical Innovations Inc.

Article 77 implementation

Curadel Surgical Innovations Inc.

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 32 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications