Viral KeratitisNCT04560790
Safety and Efficacy of CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy to Treat Refractory Viral Keratitis
A study testing BD111 Adult single group Dose in people with Viral Keratitis and Blindness Eye, run by Shanghai BDgene Co., Ltd. at 1 site in China.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of BD111 CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy administered via corneal injection in participants with refractory herpetic viral keratitis. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Viral Keratitis, Blindness Eye, Herpes Simplex Virus Infection
- What is being tested?
- BD111 Adult single group Dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteChina
- Study dates
- 4 Nov 2020to 5 Jul 2022
- Phase
- Interventional
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients (replase) with refractory keratitis caused by herpes virus type I who has had at least one time failed corneal transplant.
- Age between 18 to 70 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.
- Patients with refractory keratitis who are repeatedly infected with HSV-1 virus (more than three times per year) and resistant to topical or systemic anti-viral agents, with no response to regular immunosuppressive agents.
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- Patients who are obviously suffering from relapse HSV infections with corneal perforation, requiring corneal transplantation;
- No history of corneal trauma.
- 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, keratitis, sclerotitis, endophthalmitis) in target eye or contralateral eye within 30 days prior to enrollment.
- Ocular surface malignant tumor.
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- 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
Eye & Ent Hospital of Fudan University
Shanghai, Shanghai Municipality, 200000
About this study
Official title: CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy Assisted Corneal Transplantation in the Treatment of Refractory Viral Keratitis
The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of BD111 CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy administered via corneal injection in participants with refractory herpetic viral keratitis.
Read the detailed description
This is an open-label, single ascending dose study of BD111 in adult (ages 18 to 70) participants with refractory herpetic viral keratitis. Approximately 6 participants will be enrolled.BD111 is a novel gene editing product designed to clear Herpes simplex virus type I (HSV-1) that results in herpetic stromal keratitis in both acute and recurrent infection models which is the leading factor for infectious blindness.
The follow-up period was 360 days, and the patients will be followed up 3±1 days, 7±2 days, 30±7 days, 90±14 days, 180±21 days, and 360+31 days after treatment.
- Conditions
- Viral Keratitis, Blindness Eye, Herpes Simplex Virus Infection, Cornea
- Being tested
- BD111 Adult single group Dose
- Keywords
- Herpes simplex virus type 1 (HSV-1), CRISPR/Cas9 mRNA, instantaneous gene editing
- Medical subject headings
- Blindness, Herpes Simplex, Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BD111 Adult single group DoseDrug
3-6 Participants will receive a single group dose administered via corneal injection in the study eye.
| Study group | Role | What they receive |
|---|---|---|
| BD111 Adults single group Dose | Experimental | Administered by corneal injection surgery. Dosage form:injection solution. Dose:200uL. Frequency of administration: one time injection. Receives: Drug: BD111 Adult single group Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effective clearance of HSV-1 genome
Judge HSV-1 genome clearance effective according to DNA sequencing results by methods of Plaque assay,Elisa,PCR etc.
Measured: 12 months
Rate of reblindness in 3 participants with Refractory HSV Keratitis
180 days after corneal surgical, calculate rate of reblindness of treated eye in 3 participants.
Measured: 12 months
HSV-1 virus testing outcome of the intervention eye
Herpes virus content before and after treatment were determinated by methods of plaque assay, ELISA, PCR etc. Compare the viral content changes with baseline.
Measured: 12 months
Secondary outcomes (4)
Corneal graft survival time
Observe the survival time of grafted cornea in participants, whether the grafted cornea is transparency or opacity.
Measured: 12 months
Visual improvement compared with baseline
Judge the visual recovery progress according to visual examination results on day 3±1，7±2，30±7，90±14，180±21，360±31.
Measured: 12 months
Concentration of dose limiting toxicities
Observe and record AE,SAE incidence of dose limiting toxicities related with BD111 administration.
Measured: 12 months
Concentration of maximum tolerated dose
Observe and record AE,SAE at maximum tolerated dose when occurs dose limiting toxicities.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2020
- Study start4 Nov 2020
- Primary completion5 Jul 2022
- Study completion5 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Viral KeratitisStudies of the same condition, open and under way.
- 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group target value: Since there is no similar products approved on the market and there is no similar comparative treatment methods, the single group target value method is adopted
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai BDgene Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eye & ENT Hospital of Fudan University
- Responsible party
- Sponsor
- Investigators
- Yujia Cai, PhD, Principal investigator, Shanghai BDgene Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04560790
- Sponsor's protocol ID
- JYMS-CXL#02
- Status last verified
- Aug 2022
- First submitted
- 17 Sep 2020
- Last updated
- 24 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wei A, Yin D, Zhai Z, Ling S, Le H, Tian L, Xu J, Paludan SR, Cai Y, Hong J. In vivo CRISPR gene editing in patients with herpetic stromal keratitis. Mol Ther. 2023 Nov 1;31(11):3163-3175. doi: 10.1016/j.ymthe.2023.08.021. Epub 2023 Aug 31.
PubMed 37658603
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy Assisted Corneal Transplantation in the Treatment of Refractory Viral Keratitis
- ClinicalTrials.gov ID
- NCT04560790
- Acronym / sponsor ID
- JYMS-CXL#02
- Conditions
- Viral Keratitis, Blindness Eye, Herpes Simplex Virus Infection, Cornea
- Keywords
- Herpes simplex virus type 1 (HSV-1), CRISPR/Cas9 mRNA, instantaneous gene editing
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Shanghai BDgene Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Eye & ENT Hospital of Fudan University
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 5 Jul 2022 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 23 Sep 2020 (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, tolerability and efficacy of a single escalating doses of BD111 CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy administered via corneal injection in participants with refractory herpetic viral keratitis.
Detailed description
This is an open-label, single ascending dose study of BD111 in adult (ages 18 to 70) participants with refractory herpetic viral keratitis. Approximately 6 participants will be enrolled.BD111 is a novel gene editing product designed to clear Herpes simplex virus type I (HSV-1) that results in herpetic stromal keratitis in both acute and recurrent infection models which is the leading factor for infectious blindness.
The follow-up period was 360 days, and the patients will be followed up 3±1 days, 7±2 days, 30±7 days, 90±14 days, 180±21 days, and 360+31 days after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group target value: Since there is no similar products approved on the market and there is no similar comparative treatment methods, the single group target value method is adopted
| Arm | Type | Receives |
|---|---|---|
| BD111 Adults single group Dose | Experimental | Drug: BD111 Adult single group DoseAdministered by corneal injection surgery. Dosage form:injection solution. Dose:200uL. Frequency of administration: one time injection. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients (replase) with refractory keratitis caused by herpes virus type I who has had at least one time failed corneal transplant.
- Age between 18 to 70 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, keratitis, 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 |
|---|---|---|
| BD111 Adult single group Dose3-6 Participants will receive a single group dose administered via corneal injection in the study eye. | Drug | BD111 Adults single group Dose |
Primary outcome
Effective clearance of HSV-1 genome
Time frame: 12 months
Judge HSV-1 genome clearance effective according to DNA sequencing results by methods of Plaque assay,Elisa,PCR etc.
Rate of reblindness in 3 participants with Refractory HSV Keratitis
Time frame: 12 months
180 days after corneal surgical, calculate rate of reblindness of treated eye in 3 participants.
HSV-1 virus testing outcome of the intervention eye
Time frame: 12 months
Herpes virus content before and after treatment were determinated by methods of plaque assay, ELISA, PCR etc. Compare the viral content changes with baseline.
4 secondary outcomes
Corneal graft survival time
Time frame: 12 months
Visual improvement compared with baseline
Time frame: 12 months
Concentration of dose limiting toxicities
Time frame: 12 months
Concentration of maximum tolerated dose
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
- Derived from this study: PubMed 37658603Wei A, Yin D, Zhai Z, Ling S, Le H, Tian L, Xu J, Paludan SR, Cai Y, Hong J. In vivo CRISPR gene editing in patients with herpetic stromal keratitis. Mol Ther. 2023 Nov 1;31(11):3163-3175. doi: 10.1016/j.ymthe.2023.08.021. Epub 2023 Aug 31.
- Individual participant dataSharing planned: No
Related trials for Viral Keratitis
RecruitingPhase 1/2
Clinical Study of Intrastromal Anti-VEGF Injection for Corneal Neovascularization.
Herpes Simplex Keratitis, Corneal Neovascularization
Active, not recruitingPhase 1
A Study of the Safety, Tolerability and Prelinminary Efficacy of BD111 in Herpes Simplex Virus Type I Stromal Keratitis
Herpes Simplex Virus Type I Stromal Keratitis
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.
Yujia Cai, PhD principal investigator
Shanghai BDgene Co., Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BD111 Adult single group Dose in people with Viral Keratitis and Blindness Eye, run by Shanghai BDgene Co., Ltd. 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 9 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: finished, as of the sponsor's last update on 24 Aug 2022. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effective clearance of HSV-1 genome (time frame: 12 months). The study lists 3 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 NCT04560790, which also lists 1 linked publication.
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 24 Aug 2022.