A Phase Ⅱa Study of the Safety, Tolerability and Efficacy of BD111 in Herpes Simplex Virus Type I Stromal Keratitis
NCT Number: NCT06474442
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Herpes Simplex Virus Type I Stromal Keratitis
Interventions: GENETIC: BD111 Injection (investigational new drug)|COMBINATION_PRODUCT: Triple-drugs therapy of HSV-1 stromal keratitis
Sponsor: Shanghai BDgene Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2026-12
Locations: Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

Summary:
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.

Primary Outcome Measures: 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., 12 months
Secondary Outcome Measures: 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, 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|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"., 12 months|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., 12 months|Score change of corneal inflammation scale post-administration, From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration., 12 months|The improvement in best corrected visual acuity (BCVA), 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, From baseline to Day 70, D11ay 2, Day 180, and Day 365 post-administration., 12 months|Anti-p24 antibody in blood, At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration., 12 months|Anti-Cas9 antibody in blood, At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration., 12 months|Anti-BD111 antibody in blood, At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration., 12 months|Vector RNA copy number in tear fluid, 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, Vector persistence times: circular DNA copy number in blood at Day 112, Day 180, and Day 365 post-administration., 12 months|Off-target Detection, 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), AEs and SAEs are recorded and evaluated (type, incidance, severity etc.), including ocular and systemic AEs/SAEs post-administration., 12 months