Bacterial KeratitisEarly Phase 1ASOTARINCT06451172
Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis
A Early Phase 1 study testing ASO in people with Bacterial Keratitis and Antibiotic-resistant Bacteria, run by Eye & ENT Hospital of Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Keratitis, Antibiotic-resistant Bacteria, Infections, Bacterial
- What is being tested?
- ASO
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 11 Oct 2023to 31 Oct 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Eye & ENT Hospital of Fudan University
Shanghai, Shanghai Municipality, 200031
Jiaxu Hong, M.D.,Ph.D, +86-021-64377134, chengmingruicmr@163.com
About this study
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.
Read the 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.
- Conditions
- Bacterial Keratitis, Antibiotic-resistant Bacteria, Infections, Bacterial, Corneal Diseases, Eye Diseases, Vision Disorders
- Being tested
- ASO
- Keywords
- Bacterial Keratitis, Infections, Bacterial, Corneal Diseases, Eye Diseases
- Medical subject headings
- Bacterial Infections, Corneal Diseases, Eye Diseases, Vision Disorders, Sensation Disorders, Blindness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASODrug
Anticipated 20 Participants will receive a single group administered via eye drops in the study eye.
| Study group | Role | What they receive |
|---|---|---|
| ASO Single Group | Experimental | ASO eye drops are used through the local administration. Dosage form: eye drop solution. Dose:20uL. Frequency of administration: 3 times per day. Receives: Drug: ASO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bacteria testing outcome of the intervention eye
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.
Measured: 90 Days
Ophthalmic therapeutic effect of ASO eye drops
Measure the decrease in size, depth and infiltrate of the ulcer in millimeters by slit lamp biomicroscopy.
Measured: 90 Days
Secondary outcomes (1)
Visual improvement compared with baseline
Judge the visual recovery progress according to visual examination results on day 1，3±1，7±1，14±2，30±2，90±5.
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2024
- Study start11 Oct 2023
- Primary completion1 Oct 2024 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bacterial KeratitisStudies of the same condition, open and under way.
- More trials run by Eye & ENT Hospital of Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eye & ENT Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Soochow University
- Responsible party
- Sponsor
- Investigators
- Jiaxu Hong, M.D., Ph.D, Study director, Eye, and ENT Hospital,Shanghai Medical College, Fudan University,Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06451172
- Sponsor's protocol ID
- 202301V1
- Other IDs
- Fudan Eye and ENT Hospital
- Acronym
- ASOTARI
- Status last verified
- Jun 2024
- First submitted
- 28 May 2024
- Last updated
- 11 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Austin A, Lietman T, Rose-Nussbaumer J. Update on the Management of Infectious Keratitis. Ophthalmology. 2017 Nov;124(11):1678-1689. doi: 10.1016/j.ophtha.2017.05.012. Epub 2017 Sep 21.
PubMed 28942073Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature. 2016 Jan 21;529(7586):336-43. doi: 10.1038/nature17042.
PubMed 26791724Liu M, Chu B, Sun R, Ding J, Ye H, Yang Y, Wu Y, Shi H, Song B, He Y, Wang H, Hong J. Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter. Adv Mater. 2023 Jul;35(28):e2300477. doi: 10.1002/adma.202300477. Epub 2023 May 26.
PubMed 37002615Zhang Q, Song B, Xu Y, Yang Y, Ji J, Cao W, Lu J, Ding J, Cao H, Chu B, Hong J, Wang H, He Y. In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter. Nat Commun. 2023 Apr 22;14(1):2331. doi: 10.1038/s41467-023-37827-9.
PubMed 37087540
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis
- ClinicalTrials.gov ID
- NCT06451172
- Acronym / sponsor ID
- ASOTARI / 202301V1
- Conditions
- Bacterial Keratitis, Antibiotic-resistant Bacteria, Infections, Bacterial, Corneal Diseases, Eye Diseases, Vision Disorders
- Keywords
- Bacterial Keratitis, Infections, Bacterial, Corneal Diseases, Eye Diseases
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Eye & ENT Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- Soochow University
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 1 Oct 2024 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 11 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASO Single Group | Experimental | Drug: ASOASO eye drops are used through the local administration. Dosage form: eye drop solution. Dose:20uL. Frequency of administration: 3 times per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASOAnticipated 20 Participants will receive a single group administered via eye drops in the study eye. | Drug | ASO Single Group |
Primary outcome
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.
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.
1 secondary outcome
Visual improvement compared with baseline
Time frame: 90 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Results publication: PubMed 28942073Austin A, Lietman T, Rose-Nussbaumer J. Update on the Management of Infectious Keratitis. Ophthalmology. 2017 Nov;124(11):1678-1689. doi: 10.1016/j.ophtha.2017.05.012. Epub 2017 Sep 21.
- Results publication: PubMed 26791724Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature. 2016 Jan 21;529(7586):336-43. doi: 10.1038/nature17042.
- Results publication: PubMed 37002615Liu M, Chu B, Sun R, Ding J, Ye H, Yang Y, Wu Y, Shi H, Song B, He Y, Wang H, Hong J. Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter. Adv Mater. 2023 Jul;35(28):e2300477. doi: 10.1002/adma.202300477. Epub 2023 May 26.
- Results publication: PubMed 37087540Zhang Q, Song B, Xu Y, Yang Y, Ji J, Cao W, Lu J, Ding J, Cao H, Chu B, Hong J, Wang H, He Y. In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter. Nat Commun. 2023 Apr 22;14(1):2331. doi: 10.1038/s41467-023-37827-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiaxu Hong, M.D., Ph.D study director
Eye, and ENT Hospital,Shanghai Medical College, Fudan University,Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ASO in people with Bacterial Keratitis and Antibiotic-resistant Bacteria, run by Eye & ENT Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jiaxu Hong, M.D., Ph.D (+86-021-64377134, chengmingruicmr@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bacteria testing outcome of the intervention eye (time frame: 90 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06451172, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024.