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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
BD111: intrastromally injection, single-dosing 10E6 TU/eye, specified injection volume is 0.15mL.
Triple-drugs therapy: "Ganciclovir Eye gel+Valacilovir Tablets+Prednisolone Acetate Eye Drops" for 3 weeks.
Eye Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China
RECRUITINGClinical 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.
Time frame: 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
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".
Time frame: 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".
Time frame: 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.
Time frame: 12 months
Score change of corneal inflammation scale post-administration
From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration.
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Time frame: 12 months
The improvement in best corrected visual acuity (BCVA)
From baseline to Day 70, Day 112, Day 180, and Day 365 post-administration.
Time frame: 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.
Time frame: 12 months
Anti-p24 antibody in blood
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
Time frame: 12 months
Anti-Cas9 antibody in blood
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
Time frame: 12 months
Anti-BD111 antibody in blood
At Day 14, Day 28, Day 112, Day 180, and Day 365 post-administration.
Time frame: 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.
Time frame: 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.
Time frame: 12 months
Off-target Detection
BD111 off-target detection (DNA deep sequencing) in eye swabs at Day 14 and Day 180 post-administration
Time frame: 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.
Time frame: 12 months