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

Trial Summary

What is the purpose of this trial?

This trial tests ALM-488, a tool that helps doctors see nerves better, in patients having head and neck surgery. It highlights nerves in real-time to avoid nerve damage.

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.

What data supports the effectiveness of the treatment ALM-488 for nerve visualization during head and neck surgery?

Research on similar treatments, like the use of fluorescently labeled peptides, shows they can help identify and protect nerves during surgery, reducing the risk of nerve damage. This suggests that ALM-488, which is also a fluorescent agent, might be effective in helping surgeons see nerves better during head and neck surgeries. ^{1 2 3 4 5}

How is the drug ALM-488 unique for nerve visualization during head and neck surgery?

ALM-488 is unique because it is a fluorescently labeled peptide specifically designed to help surgeons see nerves more clearly during surgery, reducing the risk of accidental nerve damage. This is different from traditional methods that rely on white light or nerve monitoring devices, as it provides direct visual guidance. ^{3 4 6 7 8}

Research Team

Ryan Orosco, MD

Principal Investigator

University of New Mexico

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Facial nerve monitoring during parotidectomy: a systematic review and meta-analysis. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Intraoperative monitoring of marginal mandibular nerve during neck dissection. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Improved facial nerve identification during parotidectomy with fluorescently labeled peptide. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Systematic facial nerve monitoring in middle ear and mastoid surgeries: "surgical dehiscence" and "electrical dehiscence". [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Predicting postoperative facial nerve paralysis by using intraoperative nerve monitoring during parotid surgery. [2023]

6. Austria pubmed.ncbi.nlm.nih.gov

A newly designed nerve monitor for microneurosurgery: bipolar constant current nerve stimulator and movement detector with a pressure sensor. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

New methodology for facial nerve monitoring in extracranial surgeries of vascular malformations. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Facial Nerve Branching Patterns Vary With Vascular Anomalies. [2020]