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

NCT06474416 | Active Not Recruiting Phase 1

• 1 other identifier: BD-HSK-111002-Ⅰ
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

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).

Conditions

Herpes Simplex Virus Type I Stromal Keratitis

Keywords

Herpes simplex keratitis; Herpes Simplex Virus Type I; Stromal Keratitis

Outcome Measures

Primary Outcomes (4)

• 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.

  12 months

• 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.

  12 months

• 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.

  12 months

• 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.

  12 months

Secondary Outcomes (14)

• Tear fluid vector RNA

  12 months

• Tear fluid vector circular DNA

  12 months

• Blood vector circular DNA

  12 months

• Blood p24 protein

  12 months

• Blood Cas9 protein

  12 months

Other Outcomes (3)

• Anti-p24 antibody in blood

  12 months

• Anti-Cas9 antibody in blood

  12 months

• Anti-BD111 antibody in blood

  12 months

Study Arms (5)

BD111 dose 1 group

EXPERIMENTAL

1.25E+06 TU/eye

Genetic: BD111 Injection (Investigative New Drug)

BD111 dose 2 group

EXPERIMENTAL

2.5E+06 TU/eye

Genetic: BD111 Injection (Investigative New Drug)

BD111 dose 3 group

EXPERIMENTAL

5.0E+06TU/eye

Genetic: BD111 Injection (Investigative New Drug)

BD111 dose 4 group

EXPERIMENTAL

10E+06 TU/eye

Genetic: BD111 Injection (Investigative New Drug)

Positive control group

ACTIVE COMPARATOR

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

Combination Product: Triple-drugs therapy of HSV-1 stromal keratitis

Interventions

BD111 Injection (Investigative New Drug) 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).

Also known as: BD111 Lentivirus-like particles, HSV-1-erasing lentiviral particles, HELP

BD111 dose 1 group; BD111 dose 2 group; BD111 dose 3 group; BD111 dose 4 group

Triple-drugs therapy of HSV-1 stromal keratitis COMBINATION_PRODUCT

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

Also known as: Ganciclovir Ophthalmic Gel, Valacyclovir Hydrochloride Tablets, Prednisolone Acetate Ophthalmic Suspension

Positive control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years old;
• 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;
• HSV-1 nucleic acid test (qPCR method) positive;
• No use of other systemic antiviral drugs or corticosteroids within 48 hours before enrollment;
• No systemic immune diseases;
• Good eyelid structure and blinking function;
• Eye structure and function assessment showing potential for visual recovery;
• No retinal detachment;
• No history of corneal trauma;
• The best visual acuity in the fellow eye (BCVA) ≥ 38 (ETDRS);
• 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;
• Participants voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up visits.

You may not qualify if:

• 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;
• Patients with bilateral viral keratitis
• Previous corneal transplant surgery in the study eye;
• Any medicine or food allergic history;
• Absence of tear film and blinking function;
• Severe dry eye disease;
• Ocular surface tumor;
• Glaucoma;
• Patients with systemic autoimmune diseases;
• 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);
• Severe diseases in the major organs including but not limited to cardiovascular, lung, liver, kidney, or other uncontrolled diseases;
• HIV infection;
• Pregnant and lactating women (pregnancy in this trial is defined as a positive urine or blood pregnancy test);
• Participation in other drug or medical device clinical trials at present;
• Alcohol or drug abuse;

Sponsors & Collaborators

• Shanghai BDgene Co., Ltd.: lead

Study Sites (3)

Huashan Hospital, Fudan University

Shanghai, Shanghai City, 200000, China

Location

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

Location

Eye Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Keratitis, Herpetic

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Eye Infections, Viral; Eye Infections; Infections; Herpes Simplex; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Keratitis; Corneal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Wei Chen, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 25, 2024
• Study Start: September 4, 2023
• Primary Completion: October 1, 2025
• Study Completion: March 13, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

CN (3)