Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis
Overview
- Phase
- Early Phase 1
- Intervention
- ASO
- Conditions
- Bacterial Keratitis
- Sponsor
- Eye & ENT Hospital of Fudan University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Ophthalmic therapeutic effect of ASO eye drops
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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).
Arms & Interventions
ASO Single Group
ASO eye drops are used through the local administration. Dosage form: eye drop solution. Dose:20uL. Frequency of administration: 3 times per day.
Intervention: ASO
Outcomes
Primary Outcomes
Ophthalmic therapeutic effect of ASO eye drops
Time Frame: 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
Time Frame: 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 Outcomes
- Visual improvement compared with baseline(90 Days)