PRL3-zumab for neovascular (wet) age-related macular degeneration
Phase I/II Study to Assess Safety and Efficacy of PRL3-zumab in Patients With Neovascular Age-related Macular Degeneration (nAMD)
This trial tests whether three intravenous doses of PRL3-zumab given every two weeks can help people with neovascular (wet) age-related macular degeneration who have not responded to at least two standard intravitreal treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Intra-IMMUSG Pte Ltd Industry-sponsored |
| Drugs / interventions | Ranibizumab, Faricimab, Bevacizumab, zumab |
| Locations | 1 site (Singapore) |
| Trial ID | NCT07547228 on ClinicalTrials.gov |
What this trial studies
This is a single-center, randomized, placebo-controlled Phase 1/2 study at the National University Hospital, Singapore, enrolling patients with nAMD who failed at least two standard-of-care intravitreal therapies. Participants are randomized to receive PRL3-zumab 3 mg/kg, PRL3-zumab 6 mg/kg, or placebo (normal saline) intravenously every two weeks for three doses, followed by approximately 20 weeks of monitoring. Safety monitoring includes ocular and systemic adverse event surveillance using CTCAE v5, physical exams, vitals, and laboratory testing, with ocular exams at each dosing visit and every 4 weeks thereafter. Efficacy and response assessments are performed at regular intervals through week 24 post-treatment.
Who should consider this trial
Good fit: Ideal participants are adults with neovascular AMD who have failed at least two standard intravitreal therapies, are on treatment intervals of ≤8 weeks, can complete a required washout period, and can attend the Singapore study site for infusions and follow-up.
Not a fit: Patients newly responsive to standard anti-VEGF intravitreal therapy, those unable to stop current intravitreal treatment for the required washout, or those with contraindications to systemic antibody infusions are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, PRL3-zumab could stabilize or improve disease activity in patients with refractory nAMD and potentially reduce the need for frequent intravitreal injections.
How similar studies have performed: This mechanism is novel for nAMD and there are no large published trials of PRL3-zumab in nAMD, although local anti-angiogenic therapies have proven effective in this disease.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Patients with Neovascular Age-related Macular Degeneration (nAMD). 2. Willing to provide written informed consent for the study. 3. Patients undergoing intravitreal treatment having failed at least two Standard-of care treatments and be receiving ongoing intravitreal treatment at intervals of ≤ 8 weeks including Ranibizumab, Aflibercept, or Faricimab. 4. Participants receiving intravitreal treatment at screening must complete a wash-out period before enrolment. This wash-out period should be calculated based on five half-lives of the specific intravitreal treatment the participant is receiving. Below is the washing out period for some standard of care treatments. 1. Ranibizumab (half-life: 9 days) requires a wash-out period of 45 days (7 weeks) 2. Aflibercept (half-life: 11 days) requires a wash-out period of 55 days (8 weeks) 3. Faricimab (half-life: 7.5 days) requires a wash-out period of 37.5 days (5 weeks) 4. Bevacizumab (half-life: 6 days) requires a wash-out period of 30 days (4weeks) 5. Subfoveal CNV or juxtafoveal/extrafoveal CNV with a subfoveal component related to the CNV activity identified by FFA or OCT (where CNV activity is defined as showing evidence of subretinal fluid, subretinal hyperreflective material, or leakage). 6. BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye. 7. Decrease in BCVA determined to be primarily the result of nAMD or DR/DME in the study eye. 8. Presence of pigment epithelium detachment (PED), intraretinal fluid (IRF) and/or subretinal fluid (SRF) affecting the central subfield of the study eye on OCT. 9. Adequate organ (liver and renal) and hematological functions as evidenced by the laboratory results obtained within 7 days of treatment which are within the normal range for the study population, or with abnormalities deemed not clinically significant by the investigators. Exclusion Criteria: 1. Scar, fibrosis, atrophy, or retinal pigment epithelial tears involving the central fovea in the study eye. 2. Uncontrolled glaucoma (defined as IOP \>25 mmHg despite treatment with antiglaucoma medication) in the study eye. 3. History of idiopathic or autoimmune uveitis in the study eye. 4. Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery. 5. Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization. 6. Uncontrolled blood pressure (defined as systolic \>160 mmHg or diastolic \>95 mmHg). 7. Patient is receiving systemic glucocorticoids (only if higher than 10mg or equivalent of prednisolone daily) or other immunosuppressive treatment for autoimmune disease or any other medical condition.
Where this trial is running
Singapore
- NUHS Department of Ophthalmology — Singapore, Singapore (Recruiting)
Study contacts
- Study coordinator: Dr Koon Hwee Ang (David)
- Email: ang.koonhwee@intra-immusg.com
- Phone: +65 65869661
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.