Primary Open-Angle Glaucoma (POAG)
Conditions
Keywords
glaucoma, gene therapy, rho gene, trabecular meshwork, dnRhoA, IOP reduction, AAV, scAAV
Brief summary
This is an investigator initiated, single center, open label, non-randomized, exploratory clinical study. The purpose is to assess the safety and preliminary efficacy of gene therapy GVB-2001 (ScAAV2-dnRhoA) delivered via intracameral injection to the anterior segment of the eye for the treatment of subjects with primary open-angle glaucoma. At least 6 primary open angle glaucoma (POAG) patients with high intraocular pressure (IOP) will be divided into two experimental groups. The first subject was given low-dose treatment, and the follow-up subjects were determined by the Safety Review Committee (SRC). Each experimental group was given low-dose and high-dose drug treatment respectively, and low-dose or high-dose treatment was given. The optimal dose will be selected based on the trial results for future development of GVB-2001. Safety Review Committee, SRC will be set up for safety assessment of the study. The study subjects included will be 18 to 75 years of age (inclusion) and are diagnosed with primary open-angle glaucoma (POAG) for 1 year or more. Only participants who provide informed consent prior to all screening procedures will be eligible for enrollment into the trial.
Detailed description
This research plans to recruit at least 6 high intraocular pressure of primary open-angle glaucoma (POAG) patients in one clinical center and divide into two groups. Three primary glaucoma (POAG) patients with elevated intraocular pressure and no vision in the target eye will be enrolled in trial group 1. They will be divided into two dose groups: low-dose group (n = 1) and high-dose group (n = 2). The safety review committee (SRC) will determine whether to enter the high- dose group after the last subject in the low-dose group has completed the Dose limited toxicity (DLT) assessment. In group 2, 3 primary open-angle (POAG) patients with normal visual acuity and high intraocular pressure will be enrolled. The safety review committee (SRC) will determine whether to enter the low-dose group of trial group 2, and whether to enter the high-dose group of trial group 2, after the completion of the evaluation of DLT in the low-dose group of trial group 1. During the study of trial group 2, the safety review committee (SRC) will determine whether to add another optimized dose group to trial group 2, and determine the optimized therapeutic dose and the number of subjects in the optimized dose group.
Interventions
DRUGGVB-2001-high dose
GVB-2001 is a self-complementary adeno-associated viral vector (scAAV) injection to deliver human dnRhoA gene to trabecular meshwork cells in patients with primary open angle glaucoma. A single dose of high dose GVB-2001 will be injected intracamerally to the target interventional eye.
DRUGGVB-2001-low dose
GVB-2001 is a self-complementary adeno-associated viral vector (scAAV) injection to deliver human dnRhoA gene to trabecular meshwork cells in patients with primary open angle glaucoma. A single dose of low dose GVB-2001 will be injected intracamerally to the target interventional eye.
Sponsors
IVIEW Therapeutics Inc.
The First Affiliated Hospital of Soochow University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subjects volunteered to participate in the clinical study and signed written informed consent; 2. Aged 18 to 75 years old (inclusive), men and women; 3. Primary open angle glaucoma (POAG) with a history of diagnosis ≥1 year; 4. Participants in good general health and have no clinically significant systemic disease, as determined by medical history, physical examination, and screening laboratory evaluation. 5. To comply with the requirements, willing to accept all the diagnosis and treatment plan, laboratory tests and other specified testing, etc.; 6. Consent is obtained for an extended safety visit after 1 year. Special eligibility criteria for trial group 1: 1. no vision in the target eye; 2. The intraocular pressure (IOP) of the target eye was ≤50mmHg and \> 21 mmHg after combined treatment with 2 or more IOP-lowering drugs. Special inclusion criteria for trial group 2: 1. The intraocular pressure (IOP) of the target intervention eye was no more than 40mmHg, and the IOP was more than 21 mmHg after receiving combination therapy of 2 or more IOP-lowering drugs; 2. The Shaffer gonioscopy scores of the target intervention eyes were all greater than 3. 3. The best corrected distance visual acuity of the target intervention eyes was at least 0.3 (logMAR4.5) and above.
Exclusion criteria
1. Secondary glaucoma; 2. Any active or recurrent intraocular infection or inflammation, including but not limited to uveitis; 3. Severe dry eye or clinically significant active keratopathy in the target eye; 4. No intraocular pressure measurement was performed under any circumstances; 5. Allergies to drugs or their excipient to be used in clinical studies; 6. Ocular trauma in either eye within 6 months before screening, or eye surgery or nonrefractive laser therapy within 3 months before screening; 7. A clinically significant history of herpes simplex or herpes zoster keratitis; 8. A positive test for hepatitis B virus (HBV) HBsAg or HBV-DNA, hepatitis C virus (HCV) HCAb, or Epstein-Barr virus, or cytomegalovirus (CMV); 9. Syphilis antibody and HIV antibody were positive. 10. Severe active systemic bacterial, viral, fungal, malaria, or parasitic infections; 11. Any past or present malignant tumor, myeloproliferative disorder or immunodeficiency disease; 12. May interfere with the clinical significance of this study of systemic disease (including, active hepatitis, liver cirrhosis, liver fibrosis uncontrolled hypertension, myocardial infarction and myocarditis, arrhythmia, stroke, acute or chronic renal insufficiency, uncontrolled endocrine system diseases such as diabetes, thyroid function hyperfunction, Severe pulmonary hypertension, chronic obstructive pulmonary disease (copd), interstitial pneumonia, etc.); 13. Any serious mental illness; 14. Have participated in other clinical trials and received a medication or medical device intervention within 1 month before screening; 15. And women of childbearing age who are pregnant, breastfeeding, planning to become pregnant, or who are not using a medically acceptable form of birth control. Excludes women of childbearing age who have been sterilized for 1 year after menopause or 3 months after surgery; 16. Other subjects judged by the clinical investigator to be ineligible for inclusion. Special
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number and proportion of subjects with IOP ≤21mmHg | Day 28, Day 60, Day 90, 6-Month, and 12-Month after GVB-2001 administration. |
| The number and proportion of subjects whose IOP decreased by ≥20% from baseline | Day 28, Day 60, Day 90, 6-Month, and 12-Month after GVB-2001 administration. |
| Ocular adverse events (AEs) : the characteristics of AES, including endophthalmitis, eyelid edema, and corneal injection site reaction | Day 1, Day 3, Day 7, Day 14, Day 28, Day 60, Day 90, 6-Month and 12--Month after GVB-2001 administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Type, number, and incidence of systemic adverse events and serious adverse events | Adverse events (AEs): The type, number and incidence of AEs and serious adverse events (SAEs) will be analysized within 12 months after GVB-2001 administration. | — |
| The number of ocular malignancies related to GVB-2001 injection occurred after treatment | After GVB-2001 Administration up to 5 years. | — |
| RhoA protein concentration in blood | Day 7, Day 28, and 12-Month after GVB-2001 administration | — |
| RhoA protein concentration in urine | Day 7, Day 28, and 12-Month after GVB-2001 administration | — |
| RhoA protein concentration in tears | Day 7, Day 28, and 12-Month after GVB-2001 administration | — |
| AAV2 Virus Shedding in blood | Day 7, Day 28, and Month 12 after GVB-2001 administration | — |
| AAV2 Virus Shedding in urine | Day 7, Day 28, and 12-Month after GVB-2001 administration | — |
| AAV2 Virus Shedding in tears | Day 7, Day 28, and 12-Month after GVB-2001 administration | — |
| Humoral immunity response | Day 7, Day 28, and 12-Month after GVB-2001 administration | Humoral immunity response is evaluated by comprehensive judgements of IgG, IgM, IgA, complements and Light chains in blood. It's applied to assess safety. |
| Cellular immunity response | Day 7, Day 28, and 12-Month after GVB-2001 administration | Cellular immunity response is evaluated by comprehensive judgements of CD3 CD4 CD8 in blood. It's applied to assess safety. |
| AAV2 antibody titer level in blood | Day 7, Day 28, and 12-Month after GVB-2001 administration. | Compare antibody level to baseline. It's applied to assess safety. |
| Occurance of Dose limiting toxicity (DLT) as determined by the Safety Monitoring Committee (SRC) | Day 28 after GVB-2001 administration. | — |
Countries
China
Contacts
CONTACTZuliang Yao, MD
CONTACTJun Gao, MD
PRINCIPAL_INVESTIGATORPeirong Lu, MD
The First Affiliated Hospital of Soochow University
Outcome results
None listed