A Clinical Study on CRISPR/Cas9 Instantaneous Gene Editing Therapy to Primary Open-angle Glaucoma With Elevated Intraocular Pressure and MYOC Gene Mutation

BD-MMG-113001

This study will be intented to evaluate the safety and tolerability of CRISPR/Cas9 Instantaneous Gene Editing Therapy (BD113 virus-like particle, also BD113vLVP) in patients with primary open-angle glaucoma (POAG) with elevated intraocular pressure and MYOC gene mutation. The main objectives to evaluate the safety and tolerability BD113vLVP) in POAG patients with intraocular hypertension and MYOC mutation, and secondary objectives is to explore the preliminary efficacy and the preliminary metabolism characteristics of BD113vLVP in participants.

2024-06-10

2025-12-01

2025-12-01

Recruiting

9

Inclusion Criteria: 1. Signed ICF; 2. Aged 18 to 65 years old, male or female; 3. Primary open Angle glaucoma (POAG) with elevated intraocular pressure (IOP) was diagnosed with ≥1 year medical history record ; 4. Good function level of organs; 5. Good compliance and be willing to comply with the visit schedule, laboratory tests and other specified test etc. per protocol; 6. Agree to accept a long-term safety follow-up after 1 year of study. Special Inclusion Criteria for Group 1: * Target eye is no visual; * The intraocular pressure (IOP) was ≤35 mmHg and \> 21 mmHg after receiving a combination therapy of 2 or more drugs lowering IOP. Special Inclusion Criteria for Group 2: * MYOC gene mutation was detected in peripheral blood; * The intraocular pressure (IOP) was ≤30 mmHg and \> 21 mmHg after receiving a combination therapy of 2 or more drugs lowering IOP; * Both eyes have a Shaffer Angle mirror rating greater than 3. Exclusion Criteria: 1. Secondary glaucoma; 2. Any active or recurrent intraocular infection or inflammation, including but not limited to uveitis; 3. The target eye has severe dry eye or clinically significant active corneal disease; 4. Any condition not accepting the determination of IOP; 5. Any positive of human immunodeficiency virus type 1/2 (HIV-1/HIV-2) antibody, treponema pallidum (TP) specific antibody, human T-lymphotropic virus type 1 or 2 (HTLV-1/HTLV-2) antibody, or vesicular stomatitis virus G (VSV-G) antibody; 6. Any of hepatitis B virus (HBV) HbsAg or HBV-DNA, hepatitis C virus (HCV) HCAb, or epstein-barr virus (EBV), or cytomegalovirus (CMV) nucleic acid test is positive; 7. Severe active bacterial, viral, fungal, malaria or parasitic systemic infection; 8. Any past or present malignancy, myeloproliferative or immunodeficient disease; 9. History of major organ diseases or abnormalities in laboratory tests, including: 1. Liver cirrhosis, liver fibrosis or active hepatitis, and/or abnormal liver function tests (serum total bilirubin (TBIL) ≥1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥2.5×ULN; Alkaline phosphatase ≥2.5 × ULN); 2. cardiovascular and cerebrovascular diseases, including uncontrolled hypertension, myocardial infarction, myocarditis, arrhythmia, stroke, etc.; 3. kidney disease, or creatinine ≥ 1.5ULN and creatinine clearance \< 30% normal level (measured or calculated using the Cockcroft-Gault equation); 4. endocrine disorders, such as insulin-dependent diabetes mellitus, hyperthyroidism or hypothyroidism; 5. severe pulmonary hypertension, chronic obstructive pulmonary disease, interstitial pneumonia; 10. Suffering from a severe psychiatric disorders; 11. Participating in another clinical study of a drug or device, or has received the investigational drug within 42 days prior to the screening visit; 12. Pregnant or lactating women; 13. Refusing to accept any contraception measures; 14. Allergic to clinical investigational drugs or their excipients; 15. Other conditions assessed by the investigator as unsuitable for participation in this clinical study. Special Exclusion Criteria for Group 2: * Retinal diseases: complicated with unexplained quadrant blindness, neovascularization age-related macular degeneration, retinal branch vein obstruction, central retinal vein obstruction, cystoid macular edema, macular hiatal hole and central serous retinopathy; * A history of anterior chamber angle stenosis, congenital glaucoma, or angle closure, clinically significant anterior peripheral adhesion, or extensive cicatricial adhesion caused by surgery in the anterior chamber angle; * The central corneal thickness is less than 480 μm or more than 620 μm.

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ESTIMATED'}}

2024-06-19