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

June 8, 2024 updated by: Eye & ENT Hospital of Fudan University
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

20

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200031
        • Recruiting
        • Eye & ENT Hospital of Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: ASO
Anticipated 20 Participants will receive a single group administered via eye drops in the study eye.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
90 Days
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.
90 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual improvement compared with baseline
Time Frame: 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.
90 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eye & ENT Hospital of Fudan University

Collaborators

Soochow University

Investigators

  • Study Director: Jiaxu Hong, M.D., Ph.D, Eye, and ENT Hospital,Shanghai Medical College, Fudan University,Shanghai, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2023

Primary Completion (Estimated)

October 1, 2024

Study Completion (Estimated)

October 31, 2026

Study Registration Dates

First Submitted

May 28, 2024

First Submitted That Met QC Criteria

June 8, 2024

First Posted (Actual)

June 11, 2024

Study Record Updates

Last Update Posted (Actual)

June 11, 2024

Last Update Submitted That Met QC Criteria

June 8, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202301V1
  • Fudan Eye and ENT Hospital (Other Identifier: 202301V1)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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