Gene editing therapy for glaucoma patients with MYOC mutation

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

This study is testing a new gene editing therapy for glaucoma patients with a specific gene mutation to see if it can help lower eye pressure and improve their vision.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shanghai BDgene Co., Ltd. (industry)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06465537 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and preliminary efficacy of a CRISPR/Cas9 gene editing therapy (BD113 virus-like particle) in patients suffering from primary open-angle glaucoma (POAG) with elevated intraocular pressure and MYOC gene mutations. It is an open-label, single-dose, two-arm, non-randomized clinical study involving 6 to 9 participants divided into two groups based on specific criteria related to their visual acuity and MYOC mutation status. Each participant will receive a single intracameral injection of the therapy and will be monitored for safety and efficacy over a one-year follow-up period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with primary open-angle glaucoma, elevated intraocular pressure, and MYOC gene mutations.

Not a fit: Patients with secondary glaucoma or those who do not meet the specific inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option that effectively lowers intraocular pressure in glaucoma patients with MYOC mutations.

How similar studies have performed: While gene editing approaches are emerging, this specific application of CRISPR/Cas9 for treating POAG with MYOC mutations is novel and has not been extensively tested in prior studies.

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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tongren Hospital, Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Fujun Li, M.D.

Conditions: Primary Open Angle Glaucoma, primary open angle glaucoma, POAG, elevated intraocular pressure, MYOC gene mutation