Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis

Early Phase 1

Recruiting

• Conditions: Bacterial Keratitis; Antibiotic-resistant Bacteria; Infections, Bacterial; Corneal Diseases; Eye Diseases; Vision Disorders; Sensation Disorders; Blindness; Antisense Peptide Nucleic Acid; Antibacterial Therapy
• Interventions: Drug: ASO

• Registration Number: NCT06451172
• Lead Sponsor: Eye & ENT Hospital of Fudan University

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of GP-asPNA for in vivo treatment of severe antibiotic resistant bacterial keratitis.

Detailed Description

This is a study of antisense oligonucleotides (ASOs) in adult (ages 18 to 70) participants with severe antibiotic resistant bacterial keratitis. Approximately 20 participants will be enrolled.

Infectious keratitis or endophthalmitis, mainly caused by the trauma or intraocular surgical operation, has posed a grave threat to human vision health. Among them, infectious keratitis is the most common blinding keratopathy in developing countries. We develop a novel kind of Trojan strategy to specifically deliver ASOs into diverse bacteria rather than mammalian cells through the bacterial-specific ATP-binding cassette (ABC) sugar transporter. Compared with their cell-penetrating peptide counterparts, the antisense peptide nucleic acid modified with glucose polymer can be selectively internalized into human-derived multidrug- resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate.

The follow-up period was 90 days, and the patients will be followed up 1 days, 3±1 days, 7±1 days, 14±2 days, 30±2 days, and 90±5 days after treatment.

Study Timeline

• Study Start: 2023-10-11
• Study First Submitted: 2024-05-28
• Status Verified: 2024-06
• Study First Submitted QC: 2024-06-08
• Last Update Submitted: 2024-06-08
• Study First Posted: 2024-06-11
• Last Update Posted: 2024-06-11
• Primary Completion: 2024-10-01
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• The results of antimicrobial susceptibility testing in patients with bacterial keratitis showed multidrug-resistant bacterial infections, and the existing commercial antibiotics could not effectively control the disease.
• Age over 18 years.
• No systemic immune eye disease.
• Good eyelid structure and blink function.
• Exists the potential of visual recovery by evaluation of ocular structure and function.
• Subjects or their legal guardians voluntarily participate in this study, sign informed consent, good compliance and cooperation with follow-up visits.

Exclusion Criteria

• Lacrimal coating and blink function loss.
• Schirmer's test result is less than 2mm for severe dry eye disease.
• Pregnant and lactating women (pregnancy defined in this study as positive urine pregnancy test).
• Currently is involved in clinical trials of other drugs or medical devices.
• Active eye infection (including but not limited to: blepharitis, infectious conjunctivitis, sclerotitis, endophthalmitis) in target eye or contralateral eye within 30 days prior to enrollment.
• Ocular surface malignant tumor.
• A history of allergic reaction or allergy to sodium luciferin, allergy to protein products used for treatment or diagnosis, allergy to ≥ 2 drugs or non-drug factors, or current allergic disease.
• current in an infectious disease requiring oral, intramuscular or intravenous administration.
• Patients with systemic immune diseases.
• Any uncontrolled clinical problems (such as severe mental, neurological, cardiovascular, respiratory and other systemic diseases and malignant neoplasms).
• Not effective contraception.
• In uncontrolled hypertension, systolic is no less than 160 mmhg, diastolic is no less than 100 mmhg.
• In uncontrolled diabetes, fasting glucose is no less than 10.0umol/L.
• Renal insufficiency, serum creatinine is more than 133umol/L.
• Arrhythmia, myocardial ischemia, myocardial infarction (diagnosed by electrocardiogram).
• Liver dysfunction, al ANINE aminotransferase and aspartate aminotransferase levels are higher than 80 IU/L.
• Platelet level is below 100,000 /uL or above 450,000 /uL.
• Hemoglobin level is below 10.0g/dL (male) or 9.0g/dL (female).
• No anticoagulant was used, prothrombin time is higher than 16s, and thrombin time of activated part is higher than 50s.
• HIV infection (HIV-positive).
• Subjects lack compliance with the study or the ability to sign informed consent.
• There are currently signs of systemic infection, including fever and ongoing antibiotic treatment (in this study, systemic infection was defined as deviation from normal values of white blood cells, lymphocytes, and neutrophils on routine blood tests).
• Administration of Glucocorticoids and other systemic immunosuppressive drugs.
• The investigator judges other conditions unsuitable for the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ASO Single Group	ASO	ASO eye drops are used through the local administration. Dosage form: eye drop solution. Dose:20uL. Frequency of administration: 3 times per day.

Primary Outcome Measures

Name	Time	Method
Ophthalmic therapeutic effect of ASO eye drops	90 Days	Measure the decrease in size, depth and infiltrate of the ulcer in millimeters by slit lamp biomicroscopy.
Bacteria testing outcome of the intervention eye	90 Days	Assess the efficacy of bacteria clearance based on RNA sequencing data using techniques such as ELISA and PCR. For instance, real-time polymerase chain reaction (PCR) is utilized to identify 16S rRNA in corneal biopsy samples.

Secondary Outcome Measures

Name	Time	Method
Visual improvement compared with baseline	90 Days	Judge the visual recovery progress according to visual examination results on day 1，3±1，7±1，14±2，30±2，90±5.

Trial Locations

Locations (1)

Eye & ENT Hospital of Fudan University; 🇨🇳 Shanghai, Shanghai, China