Bevonescein for Nerve Visualization in Head and Neck Surgery
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alume Biosciences, Inc.
No Placebo Group
Prior Safety Data
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing a special tool called the REVEAL 475 system that helps surgeons see nerves better during certain neck surgeries. Patients will receive a dye called bevonescein that makes their nerves glow under this tool. This can help surgeons avoid damaging important nerves.
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 data supports the effectiveness of the treatment Bevonescein for nerve visualization in head and neck surgery?
Research on similar treatments shows that using near-infrared (NIR) fluorophores can help surgeons see nerves more clearly during surgery, reducing the risk of accidental nerve damage. Studies have demonstrated that these fluorophores improve nerve visibility, even when nerves are hidden under tissue, which could lead to better surgical outcomes.
12345Is Bevonescein safe for use in humans?
The research articles provided do not contain specific safety data for Bevonescein or its related names in humans.
12356How is the REVEAL 475 System treatment different from other treatments for nerve visualization in head and neck surgery?
The REVEAL 475 System is unique because it uses a fluorescent labeling technique to enhance the visibility of nerves during surgery, which can help prevent accidental nerve damage. This system provides real-time visualization of nerves, even those buried beneath tissue, which is not possible with traditional white light imaging.
13456Eligibility Criteria
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
I am at least 16 years old.
I am scheduled for surgery in my head or neck area.
My main surgery was on my salivary gland, thyroid, or neck.
Exclusion Criteria
My kidney function is reduced with a GFR less than 60 mL/min.
I have had surgery or radiation on the area where another surgery is planned.
My liver tests are slightly above normal.
My heart rhythm is irregular and not controlled by medication.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Single Arm (Bevonescein)Experimental Treatment2 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Henry Ford Health SystemDetroit, MI
University of New MexicoAlbuquerque, NM
MUSC- Hollings Cancer CenterCharleston, SC
University of PennsylvaniaPhiladelphia, PA
More Trial Locations
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Who is running the clinical trial?
Alume Biosciences, Inc.Lead Sponsor
ErgomedIndustry Sponsor
References
Clinically translatable formulation strategies for systemic administration of nerve-specific probes. [2023]Nerves are extremely difficult to identify and are often accidently damaged during surgery, leaving patients with lasting pain and numbness. Herein, a novel near-infrared (NIR) nerve-specific fluorophore, LGW01-08, was utilized for enhanced nerve identification using fluorescence guided surgery (FGS), formulated using clinical translatable strategies. Formulated LGW01-08 was examined for toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) parameters in preparation for future clinical translation. Optimal LGW01-08 imaging doses were identified in each formulation resulting in a 10x difference between the toxicity to imaging dose window. Laparoscopic swine surgery completed using the da Vinci surgical robot (Intuitive Surgical) demonstrated the efficacy of formulated LGW01-08 for enhanced nerve identification. NIR fluorescence imaging enabled clear identification of nerves buried beneath ~3 mm of tissue that were unidentifiable by white light imaging. These studies provide a strong basis for future clinical translation of NIR nerve-specific fluorophores for utility during FGS to improve patient outcomes.
First demonstration of a novel nerve-targeting fluorophore in a cohort of ex vivo human tissues. [2023]Iatrogenic nerve injury is a common complication across all surgical specialties. Better nerve visualization and identification during surgery will improve outcomes and reduce nerve injuries. The Gibbs Laboratory at Oregon Health and Science University has developed a library of near-infrared, nerve-specific fluorophores to highlight nerves intraoperatively and aid surgeons in nerve identification and visualization; the current lead agent is LGW16-03. Prior to this study, testing of LGW16-03 was restricted to animal models; therefore, it was unknown how LGW16-03 performs in human tissue. To advance LGW16-03 to clinic, we sought to test this current lead agent in ex vivo human tissues from a cohort of patients and determine if the route of administration affects LGW16-03 fluorescence contrast between nerves and adjacent background tissues (muscle and adipose). LGW16-03 was applied to ex vivo human tissue from lower limb amputations via two strategies: (1) systemic administration of the fluorophore using our first-in-kind model for fluorophore testing, and (2) topical application of the fluorophore. Results showed no statistical difference between topical and systemic administration. However, in vivo human validation of these findings is required.
Near-infrared nerve-binding fluorophores for buried nerve tissue imaging. [2021]Nerve-binding fluorophores with near-infrared (NIR; 650 to 900 nm) emission could reduce iatrogenic nerve injury rates by providing surgeons precise, real-time visualization of the peripheral nervous system. Unfortunately, current systemically administered nerve contrast agents predominantly emit at visible wavelengths and show nonspecific uptake in surrounding tissues such as adipose, muscle, and facia, thus limiting detection to surgically exposed surface-level nerves. Here, a focused NIR fluorophore library was synthesized and screened through multi-tiered optical and pharmacological assays to identify nerve-binding fluorophore candidates for clinical translation. NIR nerve probes enabled micrometer-scale nerve visualization at the greatest reported tissue depths (~2 to 3 mm), a feat unachievable with previous visibly emissive contrast agents. Laparoscopic fluorescent surgical navigation delineated deep lumbar and iliac nerves in swine, most of which were invisible in conventional white-light endoscopy. Critically, NIR oxazines generated contrast against all key surgical tissue classes (muscle, adipose, vasculature, and fascia) with nerve signal-to-background ratios ranging from ~2 (2- to 3-mm depth) to 25 (exposed nerve). Clinical translation of NIR nerve-specific agents will substantially reduce comorbidities associated with surgical nerve damage.
Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging. [2020]The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.
Improved facial nerve identification during parotidectomy with fluorescently labeled peptide. [2018]Additional intraoperative guidance could reduce the risk of iatrogenic injury during parotid gland cancer surgery. We evaluated the intraoperative use of fluorescently labeled nerve binding peptide NP41 to aid facial nerve identification and preservation during parotidectomy in an orthotopic model of murine parotid gland cancer. We also quantified the accuracy of intraoperative nerve detection for surface and buried nerves in the head and neck with NP41 versus white light (WL) alone.
Nerve-targeted probes for fluorescence-guided intraoperative imaging. [2019]A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes. Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate. Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate. Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury.