Bevonescein for Nerve Visualization in Head and Neck Surgery

Recruiting at 6 trial locations

Overseen By Kim Potter

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Alume Biosciences, Inc.

Disqualifiers: Renal impairment, Hepatic dysfunction, Cardiac issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new tool called the REVEAL 475 system, which uses bevonescein (a peptide-dye conjugate) to enhance nerve visibility during head and neck surgeries. The primary goal is to determine the tool's practicality and effectiveness for surgeries such as parotidectomy (removal of a salivary gland) or thyroidectomy (removal of the thyroid gland). Individuals planning to undergo these specific surgeries, who have not had previous surgery or radiation in the same area, might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in surgical precision.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team or your doctor for guidance.

What prior data suggests that the REVEAL 475 system is safe for nerve visualization?

Research has shown that bevonescein, administered through an IV, is generally well tolerated by patients. Early results from a first-in-human study indicated that it safely aids doctors in visualizing nerves during surgery. These studies reported no serious side effects. Thus far, patients have responded well to this treatment, suggesting it is safe for use in surgeries. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Bevonescein is unique because it enhances nerve visualization during head and neck surgery. Unlike traditional methods that rely on the surgeon's visual skills and anatomical knowledge alone, bevonescein, used with the REVEAL 475 system, illuminates nerves, potentially reducing the risk of nerve damage. This fluorescence-guided technique offers real-time visibility, which can make surgeries safer and more precise, exciting researchers and surgeons alike.

What evidence suggests that the REVEAL 475 system is effective for nerve visualization in head and neck surgery?

Research has shown that bevonescein, a substance used to highlight nerves, is safe for pre-surgery use. In this trial, all participants will receive a single administration of bevonescein. It helps facial nerves glow, which is crucial during operations. Studies have found that bevonescein can mark damaged nerves, making them easier to see and avoid. Additionally, the REVEAL 475 system, used alongside bevonescein in this trial, enhances nerve visibility, reducing the chance of nerve damage. Together, these tools improve nerve visualization and enhance surgical outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Brett Berman, MD

Principal Investigator

Chief Medical Officer

Are You a Good Fit for This Trial?

This trial is for patients undergoing head and neck surgery who may benefit from enhanced nerve visualization. Specific eligibility criteria are not provided, but typically participants would need to be suitable candidates for the surgical procedure and the investigational imaging system.

Inclusion Criteria

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

I am able to become pregnant and will take pregnancy tests during the study.

I agree to use birth control during and for 30 days after the study.

Exclusion Criteria

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

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

I have mild side effects from cancer treatment, but they are stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Pre-Surgery Preparation

Participants receive a single dose of bevonescein 500 mg via IV infusion 1-5 hours before surgery

1 day

Surgery

The REVEAL 475 system is used for nerve visualization during parotidectomy, thyroidectomy, or neck dissection surgery

1 day

Follow-up

Participants are monitored for plasma concentration of bevonescein and surgeon feedback is collected

0-12 hours after surgery

What Are the Treatments Tested in This Trial?

Interventions

• Bevonescein
• REVEAL 475 System

Trial Overview The study is testing the REVEAL 475 system used with bevonescein, a dye that helps surgeons see nerves more clearly during operations. The goal is to assess how well this technology works in making surgeries safer by improving nerve visibility.

How Is the Trial Designed?

Group I: Single Arm (Bevonescein) Experimental Treatment 2 Interventions

All patients will receive a single administration of bevonescein 500mg via IV infusion and the REVEAL 475 system will be used on all patients.

REVEAL 475 System is already approved in United States for the following indications:

Approved in United States as REVEAL 475 System for:

• Nerve visualization during head and neck surgery

Who Is Running the Clinical Trial?

Alume Biosciences, Inc.

Lead Sponsor

Trials

4

Recruited

390+

Ergomed

Industry Sponsor

Trials

11

Recruited

3,300+

Published Research Related to This Trial

The novel near-infrared (NIR) nerve-specific fluorophore, LGW01-08, significantly enhances nerve identification during surgery, allowing for the visualization of nerves buried under approximately 3 mm of tissue, which traditional white light imaging cannot achieve.

In laparoscopic swine surgeries using the da Vinci surgical robot, LGW01-08 demonstrated a favorable safety profile with a 10x difference between toxicity and effective imaging doses, supporting its potential for clinical use in fluorescence guided surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically translatable formulation strategies for systemic administration of nerve-specific probes. Barth, CW., Shah, VM., Wang, LG., et al.[2023]

The use of fluorescently labeled nerve binding peptide NP41 during parotid gland cancer surgery in mice improved the identification and preservation of facial nerves compared to traditional white light methods.

Postoperative assessments indicated that facial nerve function was better preserved with fluorescent guidance, suggesting that NP41 can enhance surgical outcomes by reducing the risk of nerve injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved facial nerve identification during parotidectomy with fluorescently labeled peptide. Hussain, T., Nguyen, LT., Whitney, M., et al.[2018]

The new small molecule fluorophore GE3126 significantly improves nerve visualization during surgery, especially in minimally invasive procedures, by enhancing the contrast of small diameter nerves against surrounding tissues.

In preclinical studies, GE3126 showed no major adverse reactions in rats and provided clear nerve imaging in a porcine model within 5 to 10 minutes of injection, maintaining visibility for up to 80 minutes, suggesting it could help prevent nerve damage during operations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging. Cotero, VE., Kimm, SY., Siclovan, TM., et al.[2020]

A novel peptide, FAM-HNP401, was identified through phage display that selectively binds to human nerves, showing a significant increase in fluorescence intensity compared to previous peptides, which could enhance nerve visibility during surgery.

The use of FAM-HNP401 in both fresh human tissue and rodent models demonstrated its potential for improving intraoperative nerve identification, which may help reduce the risk of nerve injury and associated complications during surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nerve-targeted probes for fluorescence-guided intraoperative imaging. Hingorani, DV., Whitney, MA., Friedman, B., et al.[2019]

The study tested LGW16-03, a nerve-specific fluorophore, on ex vivo human tissues to improve nerve visualization during surgery, showing no significant difference in fluorescence contrast between topical and systemic administration methods.

This research is a crucial step towards clinical application, as it aims to enhance surgical outcomes by reducing iatrogenic nerve injuries through better nerve identification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First demonstration of a novel nerve-targeting fluorophore in a cohort of ex vivo human tissues. Hebert, KA., Bateman, L., Parker, D., et al.[2023]

A new library of near-infrared (NIR) nerve-binding fluorophores was developed, allowing for precise visualization of peripheral nerves at depths of 2 to 3 mm, which is significantly deeper than what current visible light contrast agents can achieve.

In swine models, these NIR probes successfully highlighted deep lumbar and iliac nerves during laparoscopic surgery, improving the ability to avoid nerve damage and potentially reducing complications associated with surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near-infrared nerve-binding fluorophores for buried nerve tissue imaging. Wang, LG., Barth, CW., Kitts, CH., et al.[2021]

Citations

1. nature.com nature.com/articles/s41467-025-60737-x

Intraoperative nerve-specific fluorescence visualization in ... Here, we present data of a nerve imaging agent showing that preoperative intravenous infusion of bevonescein is well tolerated.

2. reporter.nih.gov reporter.nih.gov/project-details/10699258

Development of ALM-488 for nerve and ureter visualization ... Critically, ALM-488 has recently completed clinical testing for nerve delineation in open head and neck surgeries, which demonstrated that ALM-488 is safe and ...

3. journals.lww.com journals.lww.com/plasreconsurg/abstract/9900/intraoperative_real_time_fluorescence_labeling_of.2612.aspx

Intraoperative Real-Time Fluorescence Labeling of... This study demonstrates the utility of bevonescein, a fluorescein-conjugated nerve-binding peptide, in the identification of degenerated facial nerves.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05377554

NCT05377554 | Bevonescein for Intra-Operative Nerve ... This protocol describes prospective, open-label, blinded, randomized controlled, multicenter pivotal studies to evaluate ALM-488, a visualization adjunct for ...

5. firstwordpharma.com firstwordpharma.com/story/5977736

Alume Biosciences Announces Publication of Data ... “Bevonescein represents a paradigm shift in how we identify nerves during surgery, and ultimately how we improve patient outcomes.” Study ...

6. reporter.nih.gov reporter.nih.gov/project-details/10701737

Commercialization of ALM-488 for Highlighting Nerves ... ALM-488 is currently being evaluated in a clinical trial in head and neck cancer surgery patients to establish safety and efficacy for clinical use. In this ...