Bevonescein for Surgery

Overseen By Barbara Stephens

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alume Biosciences, Inc.

Disqualifiers: Prior surgery, Cardiac rhythm, Renal impairment, 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

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have an abnormal heart rhythm not controlled by medication, you may not be eligible to participate.

What data supports the effectiveness of the drug Bevonescein for surgery?

Research on similar peptide-dye conjugates shows they can effectively target specific receptors on tumors, making them useful for imaging and potentially improving surgical outcomes by highlighting tumor areas. ^{1 2 3 4 5}

How is the treatment Bevonescein unique compared to other treatments for surgery?

Bevonescein is unique because it is a peptide-dye conjugate, which may offer a novel mechanism of action by potentially enhancing visualization during surgery, unlike traditional surgical adhesives or glues that primarily focus on bonding tissues. ^{6 7 8 9 10}

What is the purpose of this trial?

Feasibility study of Bevonescein to highlight Nerves and Ureter in patients undergoing Minimally Invasive Surgery

Eligibility Criteria

This trial is for patients who are about to have minimally invasive surgery in the abdominopelvic area. The study aims to include those who could benefit from better visualization of nerves and ureters during their procedure.

Inclusion Criteria

Willing to provide informed consent

I am planning to have surgery.

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

Exclusion Criteria

Patient has a history of fluorescein allergy

Presence of a concurrent disease or condition that may interfere with study participation

Patient has a history of drug-related anaphylactic

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Defining

A dose defining phase for each surgical setting to determine the appropriate dose of Bevonescein

4 weeks

Dose Expansion

A dose expansion phase to further evaluate the safety, tolerability, and efficacy of Bevonescein

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bevonescein

Trial Overview The trial is testing Bevonescein, a substance used during surgery to make nerves and the ureter more visible. This may help surgeons avoid damaging these structures while operating.

Participant Groups

Group I: Dose Expansion Experimental Treatment 1 Intervention

A dose expansion phase for each surgical setting.

Group II: Dose Defining Experimental Treatment 1 Intervention

A dose defining phase for each surgical setting.

Who Is Running the Clinical Trial?

Alume Biosciences, Inc.

Lead Sponsor

Trials

4

Recruited

390+

Findings from Research

The study developed two peptide conjugates that effectively bind to the α(v)β(3) integrin, showing selective tumor targeting in U87MG tumor-bearing mice, which is crucial for cancer imaging and therapy.

The choice of linker between the peptide and the radiotracer significantly influenced the clearance rate from the bloodstream, while the peptides demonstrated metabolic stability, indicating potential for effective use in targeted cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and in vivo evaluation of Tc-99m-labeled cyclic CisoDGRC peptide conjugates for targeting αvβ3 integrin expression. Pathuri, G., Sahoo, K., Awasthi, V., et al.[2019]

A new antibody-drug conjugate (ADC) using a stable tripeptide linker and a sulfur-bearing maytansinoid showed enhanced cytotoxicity and bystander killing effects in targeted cancer cells, indicating its potential as an effective treatment.

In vivo studies in mice demonstrated that these ADCs had improved efficacy compared to earlier maytansinoid conjugates, suggesting that the design of the linker and side chain can significantly influence therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing. Costoplus, JA., Veale, KH., Qiu, Q., et al.[2020]

Protein and peptide conjugates are crucial in medicine for enhancing the pharmacokinetics of therapeutic and diagnostic agents, allowing for better delivery and effectiveness.

Different types of conjugates—peptide, non-targeted protein, and targeted protein—serve specific purposes, such as improving imaging contrast, increasing the half-life of drugs, and enhancing delivery to specific sites like tumors or inflamed tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of protein and peptide conjugates. Bumbaca, B., Li, Z., Shah, DK.[2023]

Novel small peptide-dye conjugates were developed that effectively target over-expressed receptors on tumors, retaining both receptor affinity and dye fluorescence properties, which is advantageous for tumor imaging.

In vivo evaluations in rat tumor models demonstrated successful specific targeting of tumors using these peptide-dye conjugates, indicating their potential as effective optical contrast agents for tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. Bugaj, JE., Achilefu, S., Dorshow, RB., et al.[2019]

Human serum albumin (HSA) can be used to create targeted bionanoparticles by forming non-covalent complexes with near-infrared (NIR) dye-labeled peptides, which can enhance imaging for surgical guidance, particularly in identifying tumor-draining lymph nodes.

The study demonstrated the effectiveness of CXCR4-targeted bionanoparticles in vivo, showcasing their potential for use in sentinel lymph node procedures, leveraging the already clinically approved HSA scaffold for rapid clinical translation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted non-covalent self-assembled nanoparticles based on human serum albumin. Bunschoten, A., Buckle, T., Kuil, J., et al.[2021]

Inappropriate use of N-butyl-2-cyanoacrylate medical glue (MG) can lead to serious postoperative complications, as demonstrated in three cases involving abdominal pain, intestinal obstruction, and foreign body formation.

Careful evaluation of the indications, dosage, and application technique of MG is crucial to prevent complications, highlighting the need for awareness and reporting of such incidents in surgical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious postoperative complications induced by medical glue: three case reports. Li, W., Xiao, M., Chen, Y., et al.[2020]

Glubran2, a cyanoacrylate glue, demonstrates superior adhesive properties and tensile strength compared to traditional fibrin glues, making it highly effective for bonding biological tissues in surgical and endoscopic procedures.

The study confirms that Glubran2 rapidly polymerizes upon contact with living tissues, creating a strong bond that is particularly beneficial in wet environments, enhancing its practical application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glubran2 surgical glue: in vitro evaluation of adhesive and mechanical properties. Kull, S., Martinelli, I., Briganti, E., et al.[2014]

The use of a modified cyanoacrylate surgical glue (NBCA+MS) for occluding the great and small saphenous veins in 90 patients showed a high effectiveness, with complete occlusion maintained in 97.8% of patients after one year.

The procedure was safe, with no cases of post-surgical thrombosis or significant side effects, and allowed patients to return to normal activities within a week, highlighting its low invasiveness and minimal pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occlusion of the Great and Small Saphenous Vein Using Copolymeric Glue Based on N-Butyl Cyanoacrylate and Methacryloxy Sulfolane. Claudio, P., Pier Luca, BA., Miriam, F.[2023]

The new light-activated surgical adhesives demonstrated significantly higher intraluminal bursting pressures (>300 mmHg) compared to traditional sutures (<150 mmHg), indicating superior strength and effectiveness in vascular tissue fusion.

Histological analysis revealed negligible thermal damage to surrounding tissues, suggesting that the laser-assisted adhesive method is safe and minimizes collateral damage, making it a promising alternative to conventional suturing techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved vascular tissue fusion using new light-activated surgical adhesive on a canine model. McNally, KM., Sorg, BS., Hammer, DX., et al.[2019]

A pilot study using a proprietary cyanoacrylate (CA) for closing superficial veins in swine models showed that the treated veins were completely occluded 30 days after the procedure, with no signs of recanalization or migration.

Histological analysis indicated that the CA caused significant changes in the vein structure, suggesting that this method is effective for vein closure and warrants further investigation into its safety and effects on surrounding tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel vein closure procedure using a proprietary cyanoacrylate adhesive: 30-day swine model results. Min, RJ., Almeida, JI., McLean, DJ., et al.[2016]

References

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

Synthesis and in vivo evaluation of Tc-99m-labeled cyclic CisoDGRC peptide conjugates for targeting αvβ3 integrin expression. [2019]

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

Peptide-Cleavable Self-immolative Maytansinoid Antibody-Drug Conjugates Designed To Provide Improved Bystander Killing. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of protein and peptide conjugates. [2023]

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

Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted non-covalent self-assembled nanoparticles based on human serum albumin. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Serious postoperative complications induced by medical glue: three case reports. [2020]

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

Glubran2 surgical glue: in vitro evaluation of adhesive and mechanical properties. [2014]

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

Occlusion of the Great and Small Saphenous Vein Using Copolymeric Glue Based on N-Butyl Cyanoacrylate and Methacryloxy Sulfolane. [2023]

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

Improved vascular tissue fusion using new light-activated surgical adhesive on a canine model. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Novel vein closure procedure using a proprietary cyanoacrylate adhesive: 30-day swine model results. [2016]