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Herpes Simplex Virus Type I Stromal KeratitisPhase 1NCT06474416

A Study of the Safety, Tolerability and Prelinminary Efficacy of BD111 in Herpes Simplex Virus Type I Stromal Keratitis

A Phase 1 study testing BD111 Injection (Investigative New Drug) and Triple-drugs therapy of HSV-1 stromal keratitis in people with Herpes Simplex Virus Type I Stromal Keratitis, run by Shanghai BDgene Co., Ltd. at 3 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This Phase I study is intended to evaluate the safety, tolerability, PK/PD profiles and preliminary efficacy via corneal intrastromal administration in patients with herpes simplex virus-1 stromal keratitis (HSK), with a dose exploration of four ascending doses of BD111 (investigative drug product). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
BD111 Injection (Investigative New Drug) and Triple-drugs therapy of HSV-1 stromal keratitis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
3 sitesChina
Study dates
4 Sep 2023to 13 Mar 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

Inclusion Criteria: Participants must meet all of the following inclusion criteria to be enrolled in this study

  1. Aged 18 to 70 years old;
  2. Clinically diagnosed patients with recurrent herpes simplex virus type I stromal keratitis (HSK). Definition of recurrence: the patient had been diagnosed with HSK and received "local antiviral eye drugs and oral antiviral drugs + local glucocorticoid eye drops" for 3 weeks with successful clinical efficacy. Before enrollment, the clinical recurrence of HSK occurred again with symptoms including tearing, photophobia, pain, blurred vision and foreign body sensation, and signs as recurrence of active inflammatory lesions examined by slit lamp;
  3. HSV-1 nucleic acid test (qPCR method) positive;
  4. No use of other systemic antiviral drugs or corticosteroids within 48 hours before enrollment;
  5. No systemic immune diseases;
  6. Good eyelid structure and blinking function;
  7. Eye structure and function assessment showing potential for visual recovery;
  8. No retinal detachment;
  9. No history of corneal trauma;
  10. The best visual acuity in the fellow eye (BCVA) ≥ 38 (ETDRS);
  11. Fertile males or females must use highly effective contraceptive methods, such as, oral contraceptives, intrauterine devices, abstinence, or barrier contraception combined with spermicides, during the trial and continue contraception for 12 months after administration;
  12. Participants voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up visits.

Exclusion Criteria: Patients with any of the following conditions cannot be enrolled in this study

  1. Active ocular infection caused by other pathogens in the target eye or the fellow eye within 30 days before enrollment, including but not limited to infectious conjunctivitis, keratitis, scleritis, and endophthalmitis;
  2. Patients with bilateral viral keratitis
  3. Previous corneal transplant surgery in the study eye;
  4. Any medicine or food allergic history;
  5. Absence of tear film and blinking function;
  6. Severe dry eye disease;
  7. Ocular surface tumor;
  8. Glaucoma;
  9. Patients with systemic autoimmune diseases;
  10. Signs of systemic infection before enrollment, including fever and receiving antibiotic treatment (systemic infection in this trial is defined as abnormal values in white blood cells, lymphocytes, and neutrophils in routine blood tests);
  11. Severe diseases in the major organs including but not limited to cardiovascular, lung, liver, kidney, or other uncontrolled diseases;
  12. HIV infection;
  13. Pregnant and lactating women (pregnancy in this trial is defined as a positive urine or blood pregnancy test);
  14. Participation in other drug or medical device clinical trials at present;
  15. Alcohol or drug abuse;
  16. Lack of compliance with the trial or the ability to sign an informed consent form;
  17. Other situations deemed unsuitable for participation in the trial by the investigator.

Trial locations and contacts

3 sites in 1 country.

China3 sites

  • The Second Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310009

  • Huashan Hospital, Fudan University

    Shanghai, Shanghai City, 200000

  • Eye Hospital of Wenzhou Medical University

    Wenzhou, Zhejiang, 310009

Other trials in China

About this study

Official title: A Multicenter, Open-label, Single Dose, Phase Ⅰ Trial to Evaluate the Safety, Tolerability and Prelinminary Efficacy of BD111 in Patients With Herpes Simplex Virus Type I Stromal Keratitis in China

This Phase I study is intended to evaluate the safety, tolerability, PK/PD profiles and preliminary efficacy via corneal intrastromal administration in patients with herpes simplex virus-1 stromal keratitis (HSK), with a dose exploration of four ascending doses of BD111 (investigative drug product).

Read the detailed description

Herpes simplex keratitis is an infectious diseases of the cornea that is primarily caused by Herpes Simplex Virus 1 (HSV-1). The stromal type, also known as HSV-1 stromal keratitis (HSK), is characterized by recurrent or chronic inflammation attributed to residual virus-triggered antigen-antibody-complement cascade reactions. BD111 is a lentivirus-like particle that is an active drug substance delivering gRNA-expressing cassettes and SpCas9 mRNA.The mechanism of action (MOA) is based on CRISPR/Cas9 gene editing technology.

This is a multicenter, open-label, dose-escalation, Phase I trial to evaluate the safety, tolerability, PK/PD profiles and preliminary efficacy of BD111 in patients with herpes simplex virus-1 stromal keratitis (HSK) in China. About 16 patients will be enrolled, dividing into open-label, four dose groups and one positive control (triple-drugs therapy) group. A rapid titration dose group combined with "3+3" dose escalation is designed for dose exploration.

Being tested
BD111 Injection (Investigative New Drug), Triple-drugs therapy of HSV-1 stromal keratitis
Keywords
Herpes simplex keratitis, Herpes Simplex Virus Type I, Stromal Keratitis
Medical subject headings
Keratitis, Herpetic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BD111 Injection (Investigative New Drug)Genetic

    Also called BD111 Lentivirus-like particles, HSV-1-erasing lentiviral particles, HELP

    BD111 Injection (Investigative New Drug) is a type of lentiviral-like particle, which can simultaneously deliver SpCas9 and gRNA targeting the HSV-1 virus gene, also known as HSV-1-erasing lentiviral particles (HELP).

  • Triple-drugs therapy of HSV-1 stromal keratitisCombination product

    Also called Ganciclovir Ophthalmic Gel, Valacyclovir Hydrochloride Tablets, Prednisolone Acetate Ophthalmic Suspension

    Triple-drugs therapy: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.

Study groups in NCT06474416
Study groupRoleWhat they receive
BD111 dose 1 groupExperimental1.25E+06 TU/eye
Receives: Genetic: BD111 Injection (Investigative New Drug)
BD111 dose 2 groupExperimental2.5E+06 TU/eye
Receives: Genetic: BD111 Injection (Investigative New Drug)
BD111 dose 3 groupExperimental5.0E+06TU/eye
Receives: Genetic: BD111 Injection (Investigative New Drug)
BD111 dose 4 groupExperimental10E+06 TU/eye
Receives: Genetic: BD111 Injection (Investigative New Drug)
Positive control groupActive comparatorTriple-drugs therapy group: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.
Receives: Combination Product: Triple-drugs therapy of HSV-1 stromal keratitis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    DLT is defined as toxicity related to BD111 observed by the investigator and sponsor during the treatment period, specifically: a) Endophthalmitis; b) Corneal perforation; c) Hypopyon; d) Other toxicities that are significantly worse than baseline or defined as ≥ Grade 4 ocular toxicity and persist for 14 days or longer, which require trial termination after discussion with the investigator and sponsor; e) Any non-ocular Grade ≥ 3 abnormality that persists for more than 1 week or requires hospitalization for medical intervention; f) death.

    Measured: 12 months

  2. Maximum tolerated dose (MTD)

    The highest dose at which ≤1/3 of the subjects experience DLT during the DLT observation period. The MTD dose must be confirmed in at least 6 subjects.

    Measured: 12 months

  3. Recommended Phase 2 dose (RP2D)

    The RP2D is determined by integrating safety, pharmacokinetic, and efficacy data from the comprehensive dose escalation. Typically, the MTD (DLT incidence ≤ 1/3) is used as the RP2D when it is confirmed, or a dose lower than the MTD is selected as the RP2D based on comprehensive data.

    Measured: 12 months

  4. Incidence and characteristics of adverse events (AE) and serious adverse events (SAE) during the study

    AE and SAE are recorded and evaluated, including eye-related AEs after treatment, such as AE at the corneal injection site.

    Measured: 12 months

Secondary outcomes (14)

  1. Tear fluid vector RNA

    Tear fluid vector RNA copy numbers detected by real-time qPCR test, is one of Pharmacokinetics indicators of main components of BD111, and analysizing results will be used to evaluated the PK profile of tear fluid vector RNA and dose-response relationship of BD111.

    Measured: 12 months

  2. Tear fluid vector circular DNA

    Tear fluid vector circular DNA copy numbers detected by real-time qPCR test, is another Pharmacokinetics indicator of main components of BD111, and analysizing results will be used to evaluated the PK profile of tear fluid vector RNA and dose-response relationship of BD111.

    Measured: 12 months

  3. Blood vector circular DNA

    Real-time qPCR test will be used to detect copy number of vector circular DNA in blood, analysizing the PK profile of blood vector circular DNA and dose-response relationship of BD111.

    Measured: 12 months

  4. Blood p24 protein

    P24 protein concentration in blood will be assayed using ELISA p24 kit at preseted timepoints, analysizing the PK profile of Blood p24 protein.

    Measured: 12 months

  5. Blood Cas9 protein

    Cas9 protein concentration in blood will be assayed using ELISA p24 kit at preseted timepoints, analysizing the PK profile of Blood p24 protein.

    Measured: 12 months

  6. Off-target Detection (Not applicable to comparison group)

    BD111 off-target test of eye swabs samples will be conducted by DNA deep sequencing at Day 0, Day6 and Day 180 post-administration.

    Measured: 12 months

  7. Antibodies to BD111-related ingredients (anti-drug antibodies, no applicable to comparison group)

    Including: a) Anti-p24 antibody in the participants' blood samples at Day 0, Day 14, Day 28, Day 180 and Day 365; b) Anti-Cas9 antibody in the participants' blood samples at Day 0, Day 14, Day 28, Day 180 and Day 365; c) Anti-BD111 antibody in the participants' blood samples at Day 0, Day 14, Day 28, Day 180 and Day 365.

    Measured: 12 months

  8. The percentage of participants with successful clearance of HSV-1 viral genome in tear at Day 14, Day 28, Day 70, Day 112, Day 180, and Day 365 post-administration

    The definition of successful HSV-1 clearance: negative results in tear swab HSV-1 nucleic acid tests on two consecutive samplings (interval ≥14 days).

    The definition of a negative result in tear swab HSV-1 nucleic acid test: single qPCR Ct value = 40 or "undetected", or Ct value of the first qPCR test "36 < Ct value < 40", and the Ct value of repetitive qPCR test is 40 or "undetected".

    Measured: 12 months

  9. The percentage of participants with failed clearance of HSV-1 viral genome in tears at Day 14, Day 28, Day 70, Day 112, Day 180, and Day 365 post-administration

    The failure of HSV-1 viral genome clearance is determinated by HSV-1 positive results of qPCR test. HSV-1 positive definition of qPCR test: qPCR Ct value ≤ 36, or qPCR Ct value is "36 < Ct value < 40" and the Ct value of repetitive qPCR test is ≤ 36, or results of both qPCR tests are "36 < Ct value < 40".

    Measured: 12 months

  10. Clinical cure rate of HSK at Day 70 and Day112 post-administration

    Definition of HSK clinical cure: disappearance of the subject's clinical symptoms, disappearance of active inflammatory lesions on ophthalmologic examinations, and successful clearance of the HSV-1 viral genome.

    Measured: 12 months

  11. The percentage of participants with HSK recurrence at Day 180, and Day 365 post-administration

    Definition of HSK recurrence: HSV-1 nucleic acid qPCR test is positive, and clinical symptoms presents again, and ophthalmic examinations find active inflammatory lesions on interventional eye.

    Measured: 12 months

  12. The score change of corneal inflammation scale post-administration

    The score changes of corneal inflammation scale will be essessed at Day 70, Day 112, Day 180, and Day 365 post-administration.

    Measured: 12 months

  13. The improvement in best corrected visual acuity (BCVA)

    From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration.

    Measured: 12 months

  14. The improvement in corrected distance visual acuity (CDVA) post-administration

    From baseline to Day 70, D11ay 2, Day 180, and Day 365 post-administration.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2024
  2. Study start4 Sep 2023
  3. Primary completionOct 2025 (estimated)
  4. Study completion13 Mar 2026 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06474416
Sponsor's protocol ID
BD-HSK-111002-Ⅰ
Status last verified
May 2025
First submitted
13 Jun 2024
Last updated
18 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BD111 Injection (Investigative New Drug) and Triple-drugs therapy of HSV-1 stromal keratitis in people with Herpes Simplex Virus Type I Stromal Keratitis, run by Shanghai BDgene Co., Ltd. at 3 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: under way, not looking for participants, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Dose-limiting toxicity (DLT) (time frame: 12 months). The study lists 4 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 NCT06474416.

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 18 May 2025.

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