CRISPR/Cas9 Instantaneous Gene Editing Therapy to Intraocular Hypertensive POAG With MYOC Mutation

Launched by SHANGHAI BDGENE CO., LTD. · Jun 13, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called CRISPR/Cas9 Instantaneous Gene Editing Therapy for people with primary open-angle glaucoma (POAG), a condition that can increase pressure inside the eye and potentially lead to vision loss. Specifically, the trial focuses on patients who have a mutation in the MYOC gene, which is linked to this type of glaucoma. The goal is to see if this new therapy is safe and if it can effectively lower eye pressure in these patients.

To participate in this trial, individuals must be between 18 and 65 years old, have been diagnosed with POAG for at least a year, and have elevated eye pressure that hasn’t been well controlled with standard treatments. Participants will receive the gene-editing therapy and will be closely monitored for safety and how well the treatment works. It’s also important to note that the study will require a long-term follow-up after one year to check on any potential side effects. If you or someone you know might be interested, discussing this with a healthcare provider can help determine if it’s a suitable option.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Signed ICF;
• • 2. Aged 18 to 65 years old;
• • 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 willing to comply with the visit schedule, laboratory tests and other specified test etc. per protocol;
• • 6. Agreeing to accept a long-term safety follow-up after 1 year of study.
• Special Inclusion Criteria for Group 1:
• • Target intervenning eye is no visual acuity;
• • 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 nucleated cells ;
• • 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 intervenning eye has severe xerophthalmia or clinically significant active corneal disease;
• • 4. Any condition no accepting the measure 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 (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. Any severe psychiatric disorders;
• • 11. Participating in another clinical study of a drug or device, or administrated 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 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/laser therapy in the anterior chamber angle;
• • The central corneal thickness is less than 480 μm or more than 620 μm.