ALM-488 for Nerve Visualization during Head and Neck Surgery

Recruiting at 6 trial locations

Overseen By Barbara Stephens

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alume Biosciences, Inc.

Disqualifiers: Radiation, Cardiac rhythm, Renal impairment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Duration: During surgery

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called ALM-488, which enhances nerve visibility during head and neck surgeries. The aim is to improve nerve identification, potentially making surgeries like parotidectomy (removal of a salivary gland) or thyroidectomy (removal of the thyroid) safer. Participants are grouped based on their cancer diagnosis, with each group receiving ALM-488 in different surgical settings. Individuals planning to undergo these specific surgeries and who can adhere to the study's guidelines might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Do I need to stop my current medications to join the trial?

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

Is there any evidence suggesting that ALM-488 is likely to be safe for humans?

Research shows that ALM-488, a special dye used to visualize nerves, is safe for patients. In earlier studies, patients who received ALM-488 did not experience serious side effects. This dye enhances nerve visibility during surgery, helping to prevent accidental nerve damage. As a fluorescent dye, ALM-488 illuminates nerves for better visibility. It is administered through an IV before surgery. The current study evaluates its safety and effectiveness for head and neck cancer surgeries. Based on past research and ongoing evaluations, it appears safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ALM-488 for nerve visualization during head and neck surgery because it offers a new way to see nerves more clearly during operations. Unlike traditional methods that rely on the surgeon's skill and experience to avoid nerve damage, ALM-488 uses a special fluorescent dye to highlight nerves, making them easier to identify. This could reduce the risk of accidental nerve damage during surgery, potentially leading to better outcomes for patients. By enhancing visibility with a fluorescent overlay, this approach may improve surgical precision and safety.

What evidence suggests that ALM-488 is effective for nerve visualization during head and neck surgery?

Research shows that ALM-488 helps surgeons see nerves during operations. Studies have found that this drug, known as bevonescein, can illuminate nerves, making them easier to identify. This is crucial in surgeries to prevent accidental nerve damage. Early results suggest that ALM-488 is safe for patients, as it does not cause harmful side effects. By highlighting nerves, ALM-488 aims to reduce the risk of nerve injury during surgery, potentially leading to better outcomes for patients. Participants in this trial will receive ALM-488, with some undergoing intraoperative nerve visualization using WLR only, while others will have WLR with FL Overlay. ^{1 2 3 6 7}

Who Is on the Research Team?

Ryan Orosco, MD

Principal Investigator

University of New Mexico

Are You a Good Fit for This Trial?

This trial is for individuals at least 16 years old who are scheduled for head and neck surgery, specifically parotidectomy, thyroidectomy, or cervical neck dissection. Participants must be able to follow the study procedures and provide consent. They should use contraception during the study if sexually active. Exclusions include allergy to fluorescein or ALM-488, prior radiation/surgery in the area, uncontrolled heart rhythm issues, severe kidney impairment, unresolved high-grade toxicity from cancer therapy, severe allergies or conditions affecting study participation.

Inclusion Criteria

I can become pregnant and agree to regular pregnancy tests during the study.

My main surgery was on my salivary gland, thyroid, or neck.

Willing and able to comply with all study procedures

Exclusion Criteria

I have had surgery or radiation on the area to be operated on.

I have side effects from cancer treatment that are not severe, except for hair loss or mild nerve pain.

I haven't had severe heart failure, a heart attack, or stroke in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALM-488 infusion for intraoperative nerve visualization during head and neck surgery

During surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALM-488

Trial Overview The trial is testing ALM-488's ability to help surgeons see nerves more clearly during head and neck surgeries by comparing two methods: using a combination of white light reflectance with fluorescence overlay versus standard white light reflectance alone.

How Is the Trial Designed?

Group I: ALM-488-002b WLR with FL Overlay Experimental Treatment 2 Interventions

Patients without a preoperative diagnosis of malignancy will be assigned to study ALM-488-002b. All patients will receive ALM-488 infusion. Intraoperative nerve visualization will be performed using WLR with FL Overlay.

Group II: ALM-488-002b WLR only Experimental Treatment 2 Interventions

Patients without a preoperative diagnosis of malignancy will be assigned to study ALM-488-002b. All patients will receive ALM-488 infusion. Intraoperative nerve visualization will be performed using WLR only.

Group III: ALM-488-002a WLR with FL Overlay Experimental Treatment 2 Interventions

Patients with a preoperative diagnosis of malignancy will be assigned to study ALM-488-002a. All patients will receive ALM-488 infusion. Intraoperative nerve visualization will be performed using WLR with FL Overlay.

Group IV: ALM-488-002a WLR only Experimental Treatment 2 Interventions

Patients with a preoperative diagnosis of malignancy will be assigned to study ALM-488-002a. All patients will receive ALM-488 infusion. Intraoperative nerve visualization will be performed using WLR only.

ALM-488 is already approved in United States for the following indications:

Approved in United States as ALM-488 for:

• Intra-operative nerve visualization in 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

Intraoperative facial nerve monitoring (FNM) significantly reduces the incidence of immediate postoperative facial nerve weakness in patients undergoing primary parotidectomy, with a decrease from 34.9% in unmonitored cases to 22.5% in monitored cases.

However, FNM does not significantly affect the long-term risk of permanent facial nerve weakness, as the rates were similar between monitored (3.9%) and unmonitored (7.1%) groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial nerve monitoring during parotidectomy: a systematic review and meta-analysis. Sood, AJ., Houlton, JJ., Nguyen, SA., et al.[2021]

Intraoperative nerve integrity monitoring (NIM) significantly reduced the incidence of marginal mandibular nerve injuries during neck dissection, with a lower paralysis rate in the NIM-assisted group (P = .021) compared to the control group.

The use of NIM did not significantly increase the duration of the surgical procedure and only resulted in a limited increase in cost, making it a valuable and efficient tool for enhancing patient safety during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative monitoring of marginal mandibular nerve during neck dissection. Tirelli, G., Bergamini, PR., Scardoni, A., et al.[2019]

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]

In a study of 100 patients undergoing middle ear and mastoid surgeries, intraoperative facial nerve monitoring (IOFNM) revealed that 43% of cases showed surgical dehiscence, indicating potential risk to the facial nerve during surgery.

The study established that an electrical stimulation threshold of 0.7 mA is effective for initial screening, while 0.4 mA is recommended for further exploration, ensuring better identification and protection of the facial nerve during these procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic facial nerve monitoring in middle ear and mastoid surgeries: "surgical dehiscence" and "electrical dehiscence". Choung, YH., Park, K., Cho, MJ., et al.[2019]

The newly designed nerve monitor allows for safe and reliable monitoring of various nerves during microneurosurgical procedures, including the facial nerve and spinal nerves, enhancing surgical precision.

This portable system, weighing only 1.8 kg, enables continuous monitoring without interrupting surgery, providing both quantitative and qualitative feedback through a display and auditory signals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A newly designed nerve monitor for microneurosurgery: bipolar constant current nerve stimulator and movement detector with a pressure sensor. Shibuya, M., Mutsuga, N., Suzuki, Y., et al.[2019]

In a study of 67 patients undergoing vascular anomaly surgeries, facial nerve (FN) branching patterns were found to differ significantly from traditional anatomical descriptions, highlighting the importance of in vivo mapping during surgery.

The study revealed that FN branches were typically adherent to hemangiomas and venous malformations, while they traveled differently through lymphatic malformations, suggesting that these conditions may alter normal nerve patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial Nerve Branching Patterns Vary With Vascular Anomalies. Adidharma, L., Bly, RA., Theeuwen, HA., et al.[2020]

Intraoperative nerve monitoring (IONM) during parotid surgery can effectively predict postoperative facial nerve paralysis (POFNP), with a high accuracy of 96.8% when using the amplitude response ratio (ARR) as a diagnostic tool.

An ARR cutoff value of 0.55 was identified, where values below this threshold indicated a significant risk of POFNP, demonstrating the method's potential for improving surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting postoperative facial nerve paralysis by using intraoperative nerve monitoring during parotid surgery. Higashino, M., Kinoshita, I., Jinnin, T., et al.[2023]

A new methodology for monitoring the facial nerve during vascular malformation surgeries significantly reduced the rate of complete facial nerve trunk injuries to only 1.5% in a study of 201 surgeries.

This approach involves preoperative mapping, continuous intraoperative monitoring of muscle responses via compound muscle action potential (CMAP), and intraoperative mapping of nerve branches, providing a reliable way to prevent nerve damage during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New methodology for facial nerve monitoring in extracranial surgeries of vascular malformations. Ulkatan, S., Waner, M., Arranz-Arranz, B., et al.[2018]

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/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 ...

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. biospace.com biospace.com/press-releases/alume-biosciences-announces-publication-of-data-examining-first-in-human-use-of-bevonescein-to-illuminate-nerves-in-nature-communications

Alume Biosciences Announces Publication of Data ... Bevonescein is a novel fluorescent visualization drug designed to selectively illuminate nerves during surgery, helping to prevent inadvertent nerve injury.

6. firstwordpharma.com firstwordpharma.com/story/5977736

Alume Biosciences Announces Publication of Data ... Bevonescein is a novel fluorescent visualization drug designed to selectively illuminate nerves during surgery, helping to prevent inadvertent ...

7. medchemexpress.com medchemexpress.com/bevonescein.html?srsltid=AfmBOopbHycFKhW8hw0lvbmua5OP60jSyHiwVCe8rSig7ubDPIZZ6Vlu

Bevonescein (ALM-488) | Peptide-Linked Tracer Bevonescein (ALM-488) is a novel, intravenously-administrated fluorescein-conjugated peptide that binds nerve-associated connective tissue, labels peripheral ...