Stopping progression and reducing retinal lesions in VEGF-resistant AMD

Phase I/IIa Clinical Study of PAL-222 Targeting Patients With Neovascular Age-related Macular Degeneration (AMD) That Shows no Response to Existing Therapy

This will try a subretinal implant called PAL-222 placed during vitrectomy to see if it is safe and helpful for people with neovascular AMD who haven't responded to anti‑VEGF treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: PharmaBio Corporation (Industry-sponsored)
• Locations: 1 site (Ube, Ymaguchi)
• Trial ID: NCT07005323 on ClinicalTrials.gov

What this trial studies

This interventional study implants a single sheet of PAL-222 into the subretinal space via pars plana vitrectomy in patients with neovascular age-related macular degeneration who have not responded to standard anti‑VEGF therapy. Participants are monitored before and after implantation for adverse events and for changes in clinical testing data, vital signs, intraocular pressure, and anterior segment findings in the treated eye. Entry requires corrected letter vision between 20 and 59 and specific retinal findings such as foveal RPE defects, macular atrophy reaching the fovea, choroidal thinning with persistent subretinal fluid, or cystoid macular degeneration with photoreceptor loss. Procedures and follow-up occur at a single center and outcomes are compared to each participant's baseline rather than to a randomized control arm.

Who should consider this trial

Good fit: Ideal candidates are people aged 50–85 with neovascular AMD unresponsive to standard treatments, corrected vision within the trial's entry range (20 to <60 letters), and specific retinal damage such as foveal RPE tears, foveal macular atrophy, choroidal thinning with persistent subretinal fluid, or cystoid macular degeneration without hard exudates or subretinal hemorrhage.

Not a fit: Patients who are responding well to anti‑VEGF therapy, have active hard exudates or subretinal hemorrhage, fall outside the vision or age ranges, or who cannot undergo vitrectomy are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the PAL-222 implant could slow disease progression and reduce damaging retinal tissue, helping preserve or improve vision in patients who no longer respond to anti‑VEGF therapy.

How similar studies have performed: Subretinal implant approaches have been tried in small early-phase studies with mixed safety and limited efficacy data, so this application remains relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

1. Patients aged between 50 and 85 years at the time of consent acquisition
2. Patients diagnosed neovascular AMD in one or both eyes
3. Patients with corrected letter vision in the subject eye of 20 letters or more (equivalent to decimal vision of 0.05) and less than 60 letters (equivalent to decimal vision of 0.32)
4. Patients who apply to one or more of the followings:

   ① RPE defect site in the RPE tear includes the Fovea

   ② The Macular atrophy confirmed by low fundus autofluorescence extends to the fovea

   ③ Patients with choroidal thinning (150 micrometer and less), subretinal fluid resistant to standard treatment, and high activity, but without hard exudated or subretinal hemorrhage which are indicators of the high risk of visual impairment.

   ④ Patients with cystoid macular degeneration with photoreceptor cell loss and intraretinal fluid above fibrovascular pigment epithelial detachment, but without hard exudates or subretinal hemorrhage.
5. Patients who had little improvement in exudative changes and no improvement, or deterioration of vision in recent two treatment with VEGF inhibitor therapy (two consecutive administration at 4-8-week intervals), after existing therapy

Exclusion Criteria:

1. Patients with fibrovascular pigment epithelial detachment (thickness 50 µm or more) in the subfoveal area in the subject eye.
2. Patients with hard exudates in the subretinal or intraretinal area in the subject eye.
3. Patients with eye infections
4. Patients with a history of retinal vascular disease other than neovascular AMD, retinal degenerative disease, rhegmatogenous retinal detachment, macular hole, premacular membrane with retinal wall, uveitis, or other ocular inflammatory disease in the subject eye.
5. Patients with optic nerve atrophy in the subject eye
6. Patients with progressive glaucoma in the subject eye (in whom intraocular pressure is not controlled, or visual field loss is progressive or has already spread to the macula)
7. Patients with severe myopia in the subject eye (axial length of 26.5 mm or more, or spherical equivalent of -7.0 D or less in phakic eyes)
8. Patients who have undergone intraocular surgery in the subject eye. (In the case of cataract surgery, patients may be enrolled if they have had no endophthalmitis or other complications, have progressed well, and more than 3 months have passed since the surgery)
9. Patients with corrected visual acuity of the non-subject eye 0.1 or less
10. Patients who are currently receiving or will receive VEGF inhibitor treatment in the non-subject eye during the study period
11. Patients with abnormal findings that pose a problem in clinical trial participation in screening tests.
12. Patients with positive HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody, syphilis serum reaction
13. Patients with allergies to human serum albumin antibiotics, trypsin
14. Patients with severe blood disorders, heart failure, liver disorders, and renal disorders
15. Patients diagnosed with malignant tumor within 5 years or patients requiring treatment
16. Pregnant women, lactating women, patients wishing to become pregnant during the trial period
17. Patients who cannot discontinue anticoagulants or antiplatelet drugs before the trial
18. Patients with drug addiction or alcoholism

Where this trial is running

Ube, Ymaguchi

• Yamaguchi University Hospital — Ube, Ymaguchi, Japan (Recruiting)

Study contacts

• Study coordinator: Hitoshi Hitoshi Kusano, M.D.

Conditions Neovascular Age-related Macular Degeneration