Phase I/II Clinical Trial of NP41 for Cranial Nerve Fluorescence Imaging

Study Overview
=================
Brief Summary
-----------------
Preclinical evidence has shown that NP41 is a novel nerve-binding peptide with safe pharmacokinetics. Fluorescently labeled NP41 is effective for the intraoperative visualization of cranial nerves during neurosurgery. This Phase I/II clinical trial is aimed to investigate the safety and validity of FAM-NP41 for the fluorescence imaging of cranial nerves. In the Phase I trial, biological safety and adverse events will be evaluated, and pharmacokinetic parameters will be measured. In the Phase II trial, the sensitivity and specificity of FAM-NP41 for the fluorescence imaging of cranial nerves will be investigated, and the signal-to-background ratio will be calculated.

Official Title
-----------------
Phase I/II Clinical Trial of NP41 Molecular Targeted Fluorescence Imaging for Cranial Nerve Visualization During Neurosurgery

Conditions
-----------------
Cranial Nerve Injuries

Intervention / Treatment
-----------------
* Drug: FAM-NP41


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Enhanced brain MRI with or without cranial CT confirms a diagnosis of tumor in the anterior skull base, the middle cranial fossa, or the posterior cranial fossa. Structural images, DTI sequences and 3D-CISS sequences confirm that the tumor is adjacent to the cranial nerve or the cranial nerve will be exposed during the neurological surgery. The body weight is within ±20% of standard body weight [0.7×(height cm-80)]kg; The preoperative laboratory examination parameters of heart, lung, liver, kidney and blood are all in the normal range; Be able to understand the potential risks and benefits of the clinical trial, and sign a written informed consent. Exclusion Criteria: Preoperative hepatorenal insufficiency: ALT or AST increased ≥ 2 times than the upper limit of normal range; serum creatinine > 2.0 mg/ dL (177 μmol/L) or glomerular filtration rate > 30 ml/min×1.73 m2; Positive reaction in the allergy test, or allergic constitution (such as allergic to two or more foods/drugs, or known to be allergic to protein or to this polypeptide); Preoperative imaging data (enhanced MRI) are incomplete; Serious primary diseases involving important organs; Mentally or physically disabled patients; Alcohol abuse or long-term medication may affect the drug metabolism; According to the judgment of the investigator, the potential intolerance to the drug (such as weak or severe malnutrition); Primary or secondary cranial nerve dysfunction, such as facial paralysis, hearing loss caused by otitis media, etc. Female patients undergoing neurosurgery during pregnancy or lactation.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FAM-NP41 Fluorescence Imaging<br>The patients will be injected with FAM-NP41 preoperatively, and fluorescence imaging of cranial nerves will be evaluated after the craniotomy. | Drug: FAM-NP41<br>* The patients will be injected with FAM-NP41 in one dose intravenously 2 hours prior to the dural incision.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters | Half-life for distribution, half-life for elimination | 0 24 hours after the drug administration | 
| Hepatorenal functions | ALT, AST, BUN, Cr, GFR | 0 72 hours after the drug administration | 
| Effectiveness for cranial nerve imaging | Sensitivity, specificity, signal-to-background ratio | Intraoperative period with cranial nerve exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Allergic reaction, changes in vital signs | 0 72 hours after the drug administration | 
| Functions of cranial nerves | Physical examination of cranial nerves | 0 1 week after the drug administration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cranial Nerve, Neurosurgery, Fluorescence Imaging, Molecular Probe, NP41