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

NCT06465537 | Recruiting

• 1 other identifier: BD-MMG-113001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Open Angle Glaucoma

Keywords

primary open angle glaucoma; POAG; elevated intraocular pressure; MYOC gene mutation

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  12 months

Secondary Outcomes (9)

• Systemic adverse events (AEs): The type, number and incidence of AEs and serious adverse events (SAEs)

  12 months

• Number and percentage of participants whose IOP decrease by ≥ 20% from baseline

  12 months

• Any ocular maligancies related to BD113vVLP

  12 months

• Changes in BCVA from baseline

  12 months

• Changes in visual fields from baseline

  12 months

Study Arms (2)

Group 1: POAG without vision for interventional eye

EXPERIMENTAL

Interventional eye of participants with POAG has no vision, with mutated or unmutated MYOC gene. Single dose of BD113vVLP will be administrated intracamerally for target interventional eye.

Genetic: BD113vVLP

Group 2: POAG with vision for interventional eye

EXPERIMENTAL

Interventional eye of participants with POAG has vision acuity, and MYOC gene mutation test is positive. Single dose of BD113vVLP will be administrated intracamerally for target interventional eye.

Genetic: BD113vVLP

Interventions

BD113vVLP GENETIC

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.

Also known as: BD113 virus-like particle, CRISPR/Cas9 mRNA instantaneous gene editing technology

Group 1: POAG without vision for interventional eye; Group 2: POAG with vision for interventional eye

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed ICF;
• Aged 18 to 65 years old;
• Primary open Angle glaucoma (POAG) with elevated intraocular pressure (IOP) was diagnosed with ≥1 year medical history record ;
• Good function level of organs;
• Good compliance and willing to comply with the visit schedule, laboratory tests and other specified test etc. per protocol;
• Agreeing to accept a long-term safety follow-up after 1 year of study.
• 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.
• 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.

You may not qualify if:

• Secondary glaucoma;
• Any active or recurrent intraocular infection or inflammation, including but not limited to uveitis;
• The target intervenning eye has severe xerophthalmia or clinically significant active corneal disease;
• Any condition no accepting the measure of IOP;
• 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;
• 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;
• Severe active bacterial, viral, fungal, malaria or parasitic systemic infection;
• Any past or present malignancy, myeloproliferative or immunodeficient disease;
• History of major organ diseases or abnormalities in laboratory tests, including:
• 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);
• Cardiovascular and cerebrovascular diseases, including uncontrolled hypertension, myocardial infarction, myocarditis, arrhythmia, stroke, etc.;
• Kidney disease, or creatinine ≥ 1.5ULN and creatinine clearance \< 30% normal level (using the Cockcroft-Gault equation);
• Endocrine disorders, such as insulin-dependent diabetes mellitus, hyperthyroidism or hypothyroidism;
• Severe pulmonary hypertension, chronic obstructive pulmonary disease, interstitial pneumonia;
• Any severe psychiatric disorders;

Sponsors & Collaborators

• Shanghai BDgene Co., Ltd.: lead
• Beijing Tongren Hospital: collaborator

Study Sites (1)

Beijing Tongren Hospital, Capital Medical University

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Glaucoma, Open-Angle; Ocular Hypertension

Condition Hierarchy (Ancestors)

Glaucoma; Eye Diseases

Study Officials

• Yufei Teng, M.D.

  Beijing Tongren Hospital

  STUDY DIRECTOR

Central Study Contacts

Fujun Li, M.D.

CONTACT

086-191 2131 1061; fujun.li@bdgene.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 20, 2024
• Study Start: June 10, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 24, 2024

Record last verified: 2024-06

Locations

CN (1)