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.
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。
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
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.
Beijing Tongren Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Ocular adverse events (AEs)
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.
Time frame: 12 months
Number and percentage of participants whose IOP decrease ≤21 mmHg
at Month 1, Month 2, Month 3, Month 6 and Month 12 after BD113vVLP administration
Time frame: 12 months
Systemic adverse events (AEs): The type, number and incidence of AEs and serious adverse events (SAEs)
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.
Time frame: 12 months
Number and percentage of participants whose IOP decrease by ≥ 20% from baseline
at Month 1, Month 2, Month 3, Month 6 and Month 12 after BD113vVLP administration
Time frame: 12 months
Any ocular maligancies related to BD113vVLP
after BD113vVLP administration
Time frame: 12 months
Changes in BCVA from baseline
at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1.
Time frame: 12 months
Changes in visual fields from baseline
at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1.
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Time frame: 12 months
Changes in RNFL from baseline
at Month 3, Month 6 and Month 12 after BD113 vVLP administration, not applicable to group 1.
Time frame: 12 months
P24 and Cas9 proteins concentration in aqueous humor
at hour 0 and Month 1 after BD113vVLP administration
Time frame: 1 months
P24 and Cas9 proteins concentration in blood
at hour 0 and Day 7 after BD113vVLP administration
Time frame: 7 days
Blood antibodies of anti-p24 protein and anti-Cas9 proteins
at Month 6 and Month 12 after BD113vVLP administration
Time frame: 12 months