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

NCT ID: NCT06474416

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-04
• Study Completion Date: 2026-03-13

Brief 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).

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.

Conditions

Herpes Simplex Virus Type I Stromal Keratitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BD111 dose 1 group

1.25E+06 TU/eye

Group Type: EXPERIMENTAL

BD111 Injection (Investigative New Drug)

Intervention Type: GENETIC

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).

BD111 dose 2 group

2.5E+06 TU/eye

Group Type: EXPERIMENTAL

BD111 Injection (Investigative New Drug)

Intervention Type: GENETIC

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).

BD111 dose 3 group

5.0E+06TU/eye

Group Type: EXPERIMENTAL

BD111 Injection (Investigative New Drug)

Intervention Type: GENETIC

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).

BD111 dose 4 group

10E+06 TU/eye

Group Type: EXPERIMENTAL

BD111 Injection (Investigative New Drug)

Intervention Type: GENETIC

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).

Positive control group

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

Group Type: ACTIVE_COMPARATOR

Triple-drugs therapy of HSV-1 stromal keratitis

Intervention Type: COMBINATION_PRODUCT

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

Interventions

BD111 Injection (Investigative New Drug)

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).

Intervention Type: GENETIC

Triple-drugs therapy of HSV-1 stromal keratitis

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

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

BD111 Lentivirus-like particles; HSV-1-erasing lentiviral particles; HELP; Ganciclovir Ophthalmic Gel; Valacyclovir Hydrochloride Tablets; Prednisolone Acetate Ophthalmic Suspension

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai BDgene Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

No. 270, West Academy Road, Wenzhou, Zhejiang, China

Locations

Huashan Hospital, Fudan University

Shanghai, Shanghai City, China

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Eye Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Countries

China

Other Identifiers

BD-HSK-111002-Ⅰ

Identifier Type: -

Identifier Source: org_study_id