Feasibility and Efficacy Study for Bevonescein-Assisted Nerve Visualization in Head & Neck Surgery

Phase 2/3 Safety and Efficacy Trial of the REVEAL 475 System for Bevonescein-Assisted Intra-Operative Visualization of Nerves in Head and Neck Surgery

A Part 1 Phase 2 feasibility study to characterize the feasibility of using the REVEAL 475 system by obtaining surgeon perspective on illumination and ease of use.

A Part 2 Phase 3 safety and efficacy study to evaluate conspicuity of the identified nerve due to bevonescein through the use of the Visualization Scoring System (VSS).

Part 1 Phase 2: All patients will receive a single dose of bevonescein 500 mg via IV infusion 1-5 hours before undergoing parotidectomy, thyroidectomy, parathyroidectomy or neck dissection surgery. The REVEAL 475 system will be evaluated for its ability to visualize nerve-fluorescence following bevonescein administration.

Part 2 Phase 3: All patients receive a single dose of bevonescein 500mg via IV infusion 1-5 hours before undergoing parotidectomy, thyroidectomy, parathyroidectomy or neck dissection surgery. During the surgery the REVEAL 475 system will be used to assess through the use of the Visualization Scoring System (VSS).

INCLUSION CRITERIA

1. Must be a minimum of 16 years of age.
2. Must be planning to undergo surgery in the Head and Neck.
3. The study participant's primary surgical treatment is parotidectomy or thyroidectomy/ parathyroidectomy (unilateral or bilateral) or cervical neck dissection.
4. Willing and able to provide written assent as required and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
5. Willing and able to comply with all study procedures.
6. Sexually active patients must be willing to use an acceptable method of contraception (e.g., double barrier method) while participating in the study and for 30 days after receiving bevonescein.
7. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had bilateral tubal ligation at least 1 year prior to screening, or who have had total hysterectomy.

EXCLUSION CRITERIA

1. The patient has a history of prior surgery and/or radiation to the intended surgical site.

2. The patient has abnormal cardiac rhythm not controlled with medication.

3. The patient has moderate to severe renal impairment as indicated by a glomerular filtration rate (GFR) < 60 mL/min.

4. The patient has decreased hepatic function defined as aspartate aminotransferase (AST)/serum glutamic/oxaloacetic transaminase (SGOT) and alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) that is higher than 20% of the institution's normal laboratory limits, and/or the patient has elevated total bilirubin that is higher than 20% of the institution's normal laboratory limits.*

5. The patient has unresolved acute toxicity from prior anti-cancer therapy grade 2 or higher, as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Alopecia, neuropathy ≤ Grade 2, as well as other nonacute and stable anti-cancer therapy toxicities are acceptable.

6. The patient has a history of fluorescein allergy.

7. The patient has a history of drug-related anaphylactic or severe allergic reactions.

8. Presence or history of any hypersensitivity to bevonescein or its excipients that, in the judgment of the investigator, places the patient at increased risk for adverse effects.

9. Presence of a concurrent disease or condition that may interfere with study participation including recent (within 6 months of screening) NYHA Class III or IV heart failure, myocardial infarction (MI) or cerebrovascular accident (CVA).

10. Presence or history of any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

11. Pregnant or breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study.

12. Use of any Investigational Product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.

    • In patients with confirmed Gilbert Syndrome, total serum bilirubin may be elevated up to 3x the institution's normal laboratory limits.