GVB-2001 gene therapy injected into the front of the eye for primary open-angle glaucoma

Proof of Concept Clinical Trial of Gene Therapy GVB-2001 Delivered Via Intracameral Injection for the Treatment of Primary Open Angle Glaucoma

This will try a gene therapy (GVB-2001) given by intracameral injection to lower high eye pressure in adults with primary open-angle glaucoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: IVIEW Therapeutics Inc. (Industry-sponsored)
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT06921317 on ClinicalTrials.gov

What this trial studies

This investigator-initiated, single-center, open-label Phase 1/2 exploratory trial will enroll at least six adults with primary open-angle glaucoma and persistently high intraocular pressure. Participants are assigned to two experimental cohorts (one with no vision in the target eye and one with preserved visual acuity) and will receive either a low or high dose of GVB-2001 (ScAAV2-dnRhoA) delivered via intracameral injection. Dose escalation and progression to higher doses are guided by a Safety Review Committee after dose-limiting toxicity assessment. The study's primary focus is safety and tolerability, with preliminary intraocular pressure measures used to inform optimal dosing for future development.

Who should consider this trial

Good fit: Adults aged 18–75 with a diagnosis of primary open-angle glaucoma for at least one year and persistently high intraocular pressure despite treatment with two or more IOP-lowering medications are the intended participants, including separate cohorts for eyes without vision and eyes with preserved visual acuity.

Not a fit: Patients with well-controlled intraocular pressure, other glaucoma subtypes, significant systemic illness, or contraindications to intraocular viral-vector injection are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, GVB-2001 could offer a longer-lasting treatment to lower intraocular pressure and reduce dependence on daily eye drops or repeated surgeries.

How similar studies have performed: AAV-based ocular gene therapies have succeeded in some retinal diseases and preclinical glaucoma models show promise, but intracameral gene therapy targeting the trabecular meshwork is early-stage and not yet proven in humans.

Eligibility criteria

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 Exclusion Criteria for trial group 1:

1\) The serum Anti-AAV2 neutralizing antibody titer was \> 1:200 at the time of screening.

Special Exclusion Criteria for trial group 2:

1. Retinal diseases that might have interfering with the study: quadrantinal blindness of unknown cause, wet age-related macular degeneration, retinal vein occlusion, cystoid macular edema, macular hole, maculopathy with neovascularization, and central serous retinopathy;
2. Narrow anterior chamber Angle, congenital Angle closure glaucoma or room, clinically significant peripheral anterior chamber adhesion or anterior chamber Angle surgery/laser treatment cause extensive catarrhal adhesion of history;
3. The central corneal thickness was less than 480μm or more than 620μm.
4. Presence of severe visual field impairment (e.g., mean deviation less than -12 dB or mean visual field defect greater than 2 dB/ year, as assessed by a perimetry analyzer)
5. The target eye had undergone intraocular anti-glaucoma surgery or anti- glaucoma laser surgery;
6. The serum Anti-AAV2 neutralizing antibody titer was \> 1:400 at the time of screening.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Principal investigator: Peirong Lu, MD — The First Affiliated Hospital of Soochow University
• Study coordinator: Zuliang Yao, MD

Conditions Primary Open-Angle Glaucoma; glaucoma; gene therapy; rho gene; trabecular meshwork; dnRhoA; IOP reduction; AAV