Primary Open Angle Glaucoma
Conditions
Keywords
primary open angle glaucoma, POAG, elevated intraocular pressure, MYOC gene mutation
Brief summary
This study is intented to evaluate the safety, tolerability and preliminary efficacy 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 metabolism characteristics of BD113vLVP in participants.
Detailed description
This is an open, single-dose, two-arm, non-randomised clinical study. A total of 6 to 9 POAG patients with high intraocular pressure were enrolled and divided into two test groups. Test Group 1 recruits 3 POAG patients, who have elevated IOP and positive or negative MYOC mutation and target interventing eye is no vision. Test Group 2 will recruit 3 to 6 POAG patients with MYOC mutations and visual acuity. In order to better verify the lowering IOP effectiveness of BD113vVLP, another 2 or 3 participants will be recruied in Group 2 on-demand. Each participant will receive single dosing BD113vVLP (4µg p24) by intracameral injection in the interventing eye, then conduct the evaluations of the safety and efficacy according to visit schedule in 1 year follow-up。
Interventions
GENETICBD113vVLP
CRISPR/Cas9 gene editing technology, called BD113vVLP (also BD113 virus-like particle) which is a developing product of gene therapy from modified third-generation integrated defective lentivirus, can deliver gRNA/Cas9 ribonucleoprotein complex (RNP). It works to knock out or knock down the mutated MYOC gene. The BD113vVLP is administrated by intracamerally injecton (sigle-dose: 4ug/p24) for each target interventional eye.
Sponsors
Shanghai BDgene Co., Ltd.
Beijing Tongren Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ocular adverse events (AEs) | 12 months | The charactaristics of ocular adverse events include endophthalmitis, hypopyon, hyphaema and corneal injection site reaction etc. will be evaluated at Week 1, Week 2, Week 3, Week 4, Month 6 and Month 12 after BD113vVLP administration. |
| Number and percentage of participants whose IOP decrease ≤21 mmHg | 12 months | at Month 1, Month 2, Month 3, Month 6 and Month 12 after BD113vVLP administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic adverse events (AEs): The type, number and incidence of AEs and serious adverse events (SAEs) | 12 months | Systemic adverse events (AEs): The type, number and incidence of AEs and serious adverse events (SAEs) will be analysized within 12 months after BD113vVLP administration. |
| Number and percentage of participants whose IOP decrease by ≥ 20% from baseline | 12 months | at Month 1, Month 2, Month 3, Month 6 and Month 12 after BD113vVLP administration |
| Any ocular maligancies related to BD113vVLP | 12 months | after BD113vVLP administration |
| Changes in BCVA from baseline | 12 months | at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1. |
| Changes in visual fields from baseline | 12 months | at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1. |
| Changes in RNFL from baseline | 12 months | at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1. |
| P24 and Cas9 proteins concentration in aqueous humor | 1 months | at hour 0 and Month 1 after BD113vVLP administration |
| P24 and Cas9 proteins concentration in blood | 7 days | at hour 0 and Day 7 after BD113vVLP administration |
| Blood antibodies of anti-p24 protein and anti-Cas9 proteins | 12 months | at Month 6 and Month 12 after BD113vVLP administration |
Countries
China
Contacts
STUDY_DIRECTORYufei Teng, M.D.
Beijing Tongren Hospital
Outcome results
None listed