Wet age-related macular degeneration (AMD) is caused by the growth of abnormal, leaky blood vessels under the central retina, leading to rapid central vision loss if untreated. It affects millions of older adults worldwide and is a leading cause of blindness in people over 50 in developed countries. Regular intravitreal injections that block VEGF have transformed outcomes, but the treatment burden of frequent injections is substantial.
What's actually going on in research
Anti-VEGF therapy — aflibercept, ranibizumab, and bevacizumab — has been the standard of care for over a decade, preserving or improving vision in most patients when initiated promptly. Faricimab, a dual inhibitor of VEGF and angiopoietin-2, is now approved and extends treatment intervals for many patients. The Port Delivery System (PDS) with ranibizumab enables continuous drug delivery through a refillable eye implant. Trials are evaluating gene therapy using AAV vectors to enable the eye to produce its own anti-VEGF protein continuously, potentially eliminating injections.
Gene therapy for continuous protection
AAV-based subretinal and suprachoroidal gene therapy to enable sustained anti-VEGF protein production by ocular cells is in phase 2/3 trials, with the potential to eliminate recurring injections.
Bispecific antibody therapy
Faricimab, targeting both VEGF-A and angiopoietin-2, is now approved and extends injection intervals to 12–16 weeks in many patients; follow-on bispecific agents are in trials.
Sustained delivery implants
The Port Delivery System and similar refillable ocular implants are being studied to maintain continuous therapeutic drug levels and reduce the frequency of office visits and injections.
What to know before you search
Eligibility typically requires confirmed wet AMD with active choroidal neovascularization, measurable vision loss, and often defined prior anti-VEGF treatment history.
What types of trials are currently open
- Gene therapy trials — AAV-delivered anti-VEGF gene constructs to enable sustained ocular protein production without injections.
- Extended-interval biologic trials — Testing new bispecific antibodies and formulations that maintain vision with less frequent dosing.
- Sustained delivery device trials — Evaluating refillable intraocular implants providing continuous ranibizumab or aflibercept exposure.
- Combination anti-VEGF trials — Studying multi-target anti-angiogenic drug combinations for patients with incomplete response to single-agent therapy.
- Neuroprotection trials — Testing agents to protect photoreceptors and retinal cells from damage beyond just blocking new vessel growth.
Recently added Wet Age-related Macular Degeneration trials
A Study of PRL3-zumab in Neovascular Age-related Macular Degeneration (nAMD)
Study Design This is a Single-center, Phase I/II placebo-controlled study to assess the safety and efficacy of PRL3-zumab in patients with Neovascular Age-related Macular Degeneration (nAMD). PRL3-zumab will be administered intravenously in 2-week interval for 3 doses. Normal saline (0.9% Sodium Chloride w/v) will be used in placebo treatment. The study will consist of 3 arms. Arm-1: PRL3-zumab 3mg/kg intravenously will be administered in 2 week interval followed by 20 weeks of monitoring (n=6) Arm-2: PRL3-zumab 6mg/kg intravenously will be administered in 2 week interval followed by 20 weeks of monitoring (n=6) Arm-3: Placebo (normal saline 0.9% sodium chloride w/v) intravenously will be administered in 2 week interval followed by 20 weeks of monitoring (n=3) Initial 3 arms will be conducted on patients who failed Standard-of-Care (SOC) therapy. Response assessment will be done at every 4 weeks from last dose of treatment till 24-week. Randomization: Randomization will be done in 2:2:1 manner on PRL3-zumab (Arm 1), 3mg/kg (n=6); PRL3-zumab (Arm 2), 6mg/kg (n=6); and placebo group (Arm 3) (n=3). Randomization can be achieved using random number table which will be prepared before the commencement of clinical trial. The allocation of participants will be done by Investigator and will be concealed from the participants. Blinding: Single blinding will be done for this trial in which all participants are unaware of their treatment assignment. No blinding will be done on Investigator. Primary Endpoints: 1. Safety: • Adverse Events: Frequency and severity of adverse events throughout the primary outcome assessment period will be assessed by the Investigator for severity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 or later 2. RP2D: • This study will confirm Recommended Phase 2 DOse (RP2D) established from Phase I Clinical Trial in Cancer patients conducted in National University Hospital Singapore (MC/03/0616). 3. Efficacy: * Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. Change in BCVA letter gain of 0-4 will be considered as primary end point. * Change From Baseline in Central Subfield Retinal Thickness (CST) measured by Optical Coherence Tomography (OCT). \[Assessment Time Frame: 4 weekly through 24 weeks\] Secondary endpoints: * Change in visual Acuity (Best Corrected Visual Acuity) of 5 or more letters. * Proportion of patients gaining ≥15, ≥10, ≥5, or ≥0 ETDRS letters in BCVA from baseline over time * Proportion of patients avoiding a loss of ≥15, ≥10, or ≥5 ETDRS letters in BCVA from baseline over time * Proportion of patients with absence of intraretinal fluid measured by OCT * Proportion of patients with absence of subretinal fluid measured by OCT \[Assessment Time Frame: 4 weekly through 24 weeks\] Criteria for additional Therapy: Once the treatment is stopped after the third dose, patients from all groups are eligible for additional therapy as open-label treatment if there is recurrence of disease activity, as defined by presence of any of the following criteria: 1. Decrease of ≥5 letters in BCVA compared with average BCVA value over the previous two scheduled visits, owing to nAMD disease activity (as determined by the investigator). 2. Increase of \>50 µm in OCT-measured CST compared with the average CST value over the previous two scheduled visits. 3. Recurrence of intra-retinal or sub-retinal fluid (if resolved previously) 4. New macular hemorrhage Patients in the placebo group will be given PRL3-zumab (6mg/kg) if they fulfil the criteria for additional therapy. Additional therapy will be continued in subsequent monitoring visit until the progression of disease, or end of the trial. If patients show clinical benefit from the treatment, additional doses could be given based on investigators' judgment. Criteria for progression of disease: 1. BCVA decreases by 15 letters or more from best recorded BCVA because of nAMD disease activity. 2. an increase in OCT central retinal thickness 150 µm or more from lowest recorded measurement after 2 consecutive additional therapy occurring 1 month apart.
A Clinical Trial of EYE201/MK-8748 in People With Macular Degeneration (MK-8748-003)
Researchers are looking for new ways to treat neovascular age-related macular degeneration (NVAMD). Available standard (usual) treatments for NVAMD, such as aflibercept, may not work for every person. Researchers want to learn if a trial medicine called tiespectus (also called MK-8748 or EYE201) can treat NVAMD. The goal of this trial is to learn if tiespectus works as well as aflibercept to treat NVAMD.
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