The goal of this clinical trial is to evaluate the safety and tolerability of a single dose of ER-100 in adults with optic nerve conditions, specifically Open Angle Glaucoma (OAG) and Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION). The main questions it aims to answer are:
* Is ER-100 safe when given as a single dose to people with OAG or NAION * What side effects may occur, if any, after taking ER-100?
Participants will:
* Receive a single dose of ER-100 * Undergo safety assessments including detailed eye examination and laboratory tests * Provide body fluid samples (tears, saliva, feces, urine) to help researchers understand how the drug is processed and cleared from the body * Complete questionnaires about their quality of life * Be followed for up to 5 years to monitor long-term health and vision outcomes
Have clear eye structures and be able to have your pupils safely dilated so the doctor can examine the back of your eye.
Able to understand the study and sign a consent form.
Be between 40 and 85 years old.
Willing and able to follow the study schedule, including all visits and tests, and speak a language for which the study materials are available.
History of optic neuritis (inflammation of the optic nerve) or repeated episodes of eye inflammation (uveitis) not caused by injury or surgery.
Allergic reactions to tetracycline antibiotics or steroid medications.
Moderate to severe cataracts, macular problems, or corneal issues that could interfere with eye testing.
Unable to keep your eyes focused on a target during testing.
Sequential
ER-100 epigenetic therapy
GeneticER-100 is an investigational AAV-based epigenetic therapy administered via intravitreal injection to one eye. It uses a modified adeno-associated virus (AAV) vector to deliver instructions for producing three transcription factors-OCT4, SOX2, and KLF4 (collectively referred to as OSK)-intended to reverse age-related epigenetic changes in retinal cells. Systemic doxycycline is administered for 8 weeks (56 days) to activate OSK expression. ER-100 does not alter the participant's existing genes, and the AAV vector has been engineered to eliminate its ability to cause infectious disease.
Incidence of Treatment-Emergent Adverse Events (TEAEs) During and Post-Doxycycline Activation Period
This outcome tracks any new or worsening health problems that occur while participants are receiving and completed oral doxycycline. These health problems are called treatment-emergent adverse events (TEAEs). Researchers record how often these events happen as well as their nature and seriousness. This helps determine whether ER-100 causes any short-term side effects during this phase.
Incidence of Dose-Limiting Toxicities During and Post-Doxycycline Activation Period
This outcome measures how often participants experience dose-limiting toxicities, which are side effects serious enough to prevent increasing the dose, while receiving and completed oral doxycycline. These toxicities are defined by the study protocol and may differ for participants with open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION). This helps identify the highest dose that can be given safely during treatment.
Change in Safety Laboratory Tests (Liver Function Tests - LFTs) During and Post-Doxycycline Activation Period
Liver function tests (LFTs) measure specific enzymes and proteins in a blood sample to check how well the liver is working. These include alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH). When liver cells are injured, these enzymes leak into the bloodstream, and higher levels on a blood test can signal a problem. Compared to baseline, higher levels can mean the liver is under stress or injured. Unit of Measure: Units per liter (U/L)
Change in Safety Laboratory Tests (Blood Protein Levels) During and Post-Doxycycline Activation Period
Blood proteins such as albumin and total protein help show nutritional status and how well the liver is making proteins. Compared to baseline, lower levels can mean poor nutrition or liver problems. Unit of Measure: Grams per deciliter (g/dL)
Change from Baseline in the Intraocular Pressure (IOP) in the Treated Eye During and Post-Doxycycline Activation Period - Efficacy
This outcome measures the change in pressure inside the treated eye while participants are receiving and completed oral doxycycline. Eye pressure is measured in millimeters of mercury (mmHg). On Day 1, pressure is measured using an instrument named Goldmann Applanation Tonometry (GAT), which is the gold standard. This instrument will gently touch the eye with a probe after applying numbing drops. After Day 1, pressure is measured using another, non-contact method, which uses a puff of air. If pressure increases significantly, GAT may be repeated to confirm. Lower pressures compared to baseline may indicate disease improvement.
Change from Baseline in the Intraocular Pressure (IOP) in the Treated Eye - Long-term Follow-up Period - Safety
This outcome measures changes in pressure inside the treated eye after participants stop taking oral doxycycline during the long-term follow-up period. Eye pressure is measured in millimeters of mercury (mmHg). On Day 1, pressure is measured using Goldmann Applanation Tonometry (GAT), which gently touches the eye with a probe after applying numbing drops. After Day 1, pressure is measured using non-contact tonometry, which uses a puff of air. If pressure increases significantly, GAT may be repeated to confirm. Depending on their values, higher or significantly lower pressures compared to the participant's baseline may indicate progression or need for further safety monitoring.
Change from Baseline in the Best Corrected Visual Acuity (BCVA) Letter Score in the Treated Eye During and Post-Doxycycline Activation Period - Efficacy
This outcome measures the change in visual clarity (corrected with glasses or contact lenses for refractive errors like nearsightedness, farsightedness, or astigmatism) in the treated eye while participants are receiving and completed oral doxycycline. This outcome measures whether visual clarity improves in the treated eye while participants are receiving oral doxycycline. BCVA is assessed using a special chart called the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The number of letters read correctly is recorded as a letter score, ranging from 0 to 100. An increase in score from the baseline may suggest the treatment is helping improve how well someone sees. Trial frames with the lens prescription determined at screening will be used for these assessments.
Change from Baseline in the Best Corrected Visual Acuity (BCVA) Letter Score in the Treated Eye - Long-term Follow-up Period - Safety
This outcome measures the change in visual clarity (corrected with glasses or contact lenses for refractive errors like nearsightedness, farsightedness, or astigmatism) in the treated eye after participants stop taking oral doxycycline during the long-term follow-up period. BCVA is assessed using a special chart called Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The number of letters read correctly is recorded as a letter score, ranging from 0 to 100. A drop in score from baseline may indicate a safety issue affecting vision, while stable or improved scores suggest no adverse impact. Trial frames with the lens prescription determined at screening will be used for these assessments.
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