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

May 14, 2025 updated by: Shanghai BDgene Co., Ltd.

A Multicenter, Single-blind, Single-dose, Randomized, Phase Ⅱa Trial to Evaluate the Safety, Tolerability and Efficacy of Intrastromal BD111 Gene Editing Therapy in Adults With HSV-1 Stromal Keratitis

This study aims to compare the clinical efficacy and safety of BD111 injection in combination with standard therapy vs. standard therapy in herpes simplex virus type I stromal keratitis (HSK), providing preliminary confirmation of the clinical effectiveness of BD111 in combination with standard therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase Ⅱa, single-blind, single-dose, randomized, positively controlled clinical trial of BD111 in patients with herpes simplex virus type I stromal keratitis (HSK) aged 18 to 70 years. Forty eligible participants will be recruited in the trial. BD111 is investigational new biologics (Injection)--a type of lentiviral-like particle that can simultaneously deliver SpCas9 and gRNA targeting the HSV-1 virus gene, also known as HSV-1-erasing lentiviral particles (HELP). The total follow-up duration was 12 months, the safe endpoints and efficacy endpoints will be used to assess the efficacy, safety and tolerability profiles in patients with HSK.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

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 Contact Backup

Study Locations

  • China
    • Zhejiang
      • Wenzhou, Zhejiang, China
        • Recruiting
        • Eye Hospital of Wenzhou Medical University
        • Contact:
        • 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: 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 with herpes simplex virus stromal keratitis;
  3. Tear swab HSV-1 nucleic acid test (qPCR method) positive;
  4. No use of systemic antiviral drugs or corticosteroids within 48 hours before enrollment;
  5. No systemic immune eye diseases;
  6. Good eyelid structure and blinking function;
  7. Eye structure and function assessment showing potential for visual recovery;
  8. No retinal detachment, with generally normal visual function;
  9. No history of corneal trauma;
  10. Visual acuity in the fellow eye is better than 20/200;
  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 blepharitis, infectious conjunctivitis, keratitis, scleritis, and endophthalmitis;
  2. Patients with bilateral viral keratitis
  3. Previous corneal transplant surgery in the study eye;
  4. A history of adverse reactions or allergies to corticosteroids and sodium fluorescein, allergies to therapeutic or diagnostic protein products, allergies to ≥ two drugs or non-drug factors, or having an ongoing allergic disease;
  5. Absence of tear film and blinking function;
  6. Severe dry eye disease;
  7. Malignant ocular surface tumor;
  8. Glaucoma;
  9. Patients with systemic autoimmune diseases;
  10. Signs of systemic infection before enrollment, including fever and receiving antibiotic treatment (abnormal elevating values in white blood cells, lymphocytes, and neutrophils in routine blood tests);

  11. Abnormal major organ function or other uncontrolled clinical problems, mainly including but not limited to the following:

    • Severe kidney disease history, serum creatinine ≥ 133μmol/L;
    • Liver dysfunction, transaminase level ≥ 80 IU/L;
    • Uncontrolled hypertension, systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg;
    • Uncontrolled diabetes, fasting blood glucose greater than or equal to 8.0 μmol/L;
    • Cardiovascular disease history, with arrhythmia, myocardial ischemia, and myocardial infarction (diagnosed by electrocardiogram examination);
    • Platelet level ≤ 100×10^9/μL or ≥ 450×10^9/μL due to any cause, hemoglobin level lower than 10.0g/dL (male) or 9.0g/dL (female).
  12. HIV infection;
  13. Pregnant and lactating women (pregnancy in this trial is defined as a positive urine pregnancy test);
  14. Participation in other drug or medical device clinical trials;
  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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
BD111 combining triple-drugs therapy Group.
Combination product: Triple-drugs therapy of HSV-1 stromal keratitis
Triple-drugs therapy: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.
Other Names:
  • Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops
Genetic: BD111 Injection (investigational new drug)
BD111: intrastromally injection, single-dosing 10E6 TU/eye, specified injection volume is 0.15mL.
Other Names:
  • BD111 Lentivirus-like particles, also called HSV-1-erasing lentiviral particles (HELP)
Active Comparator: Group 2
BD111 sham injection combining triple-drugs therapy group.
Combination product: Triple-drugs therapy of HSV-1 stromal keratitis
Triple-drugs therapy: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.
Other Names:
  • Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical cure rate of HSK at Day 70 and Day112 post-administration
Time Frame: 12 months
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 12 months
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".
12 months
The percentage of participants with HSK recurrence at Day 180, and Day 365 post-administration
Time Frame: 12 months
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.
12 months
The improvement in best corrected visual acuity (BCVA)
Time Frame: 12 months
From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration.
12 months
The improvement in corrected distance visual acuity (CDVA) post-administration
Time Frame: 12 months
From baseline to Day 70, D11ay 2, Day 180, and Day 365 post-administration.
12 months
The percentage of participants with successful clearance of HSV-1 viral genome in tears at Day 14, Day 28, Day 70, Day 112, Day 180, and Day 365 post-administration
Time Frame: 12 months

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".
12 months
Score change of corneal inflammation scale post-administration
Time Frame: 12 months
From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration.
12 months
Anti-p24 antibody in blood
Time Frame: 12 months
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
12 months
Anti-Cas9 antibody in blood
Time Frame: 12 months
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
12 months
Anti-BD111 antibody in blood
Time Frame: 12 months
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
12 months
Vector RNA copy number in tear fluid
Time Frame: 12 months
Vector persistence times: Tear fluid vector RNA copy number at Day 112, Day 180, and Day 365 post-administration.
12 months
Circular DNA copy number in blood
Time Frame: 12 months
Vector persistence times: circular DNA copy number in blood at Day 112, Day 180, and Day 365 post-administration.
12 months
Off-target Detection
Time Frame: 6 months
BD111 off-target detection (DNA deep sequencing) in eye swabs at Day 14 and Day 180 post-administration
6 months
The characteristics of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 12 months
AEs and SAEs are recorded and evaluated (type, incidance, severity etc.), including ocular and systemic AEs/SAEs post-administration.
12 months

Collaborators and Investigators

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

Sponsor

Shanghai BDgene Co., Ltd.

Investigators

  • Study Director: Fujun Li, M.D., Shanghai BDgene Co., Ltd.

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)

April 28, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

June 13, 2024

First Submitted That Met QC Criteria

June 19, 2024

First Posted (Actual)

June 25, 2024

Study Record Updates

Last Update Posted (Actual)

May 18, 2025

Last Update Submitted That Met QC Criteria

May 14, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BD-HSK-111002-Ⅱa

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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