Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy (Optic Nerve Conditions)

Browse trials for

• Glaucoma, Open-Angle 924
• Optic Nerve Diseases 61
• Retinal Diseases 333

Keywords

• Optic Neuropathy
• Retinal Diseases
• Aging/Cellular Aging
• Open-Angle Glaucoma
• Non-Arteritic Anterior Ischemic Optic Neuropathy
• Partial Epigenetic Reprogramming
• Epigenetic Therapy

Glaucoma, Open-Angle

924 studies on the registry are indexed under Glaucoma, Open-Angle; 117 are open to participants now.

This study's planned enrollment of 18 is below the median of 80 across 692 interventional studies indexed under Glaucoma, Open-Angle.

Lead sponsor

This is the only study on the registry with Life Biosciences Inc. as lead sponsor.

Study arms

• Experimental
  OAG - Low Dose ER-100 (2 x 10^11 vg/eye)

  Participants with Open Angle Glaucoma will receive a low dose of ER-100 administered to one eye. ER-100 is delivered via a modified adeno-associated virus (AAV) vector and activated by systemic doxycycline taken for 8 weeks (56 days). This dose level begins with a sentinel participant followed by additional participants after DSMB review.

  Genetic: ER-100 epigenetic therapy

• Experimental
  OAG - High Dose ER-100 (6 x 10^11 vg/eye)

  Participants with Open Angle Glaucoma will receive a higher dose of ER-100 administered to one eye. ER-100 is delivered via a modified AAV vector and activated by systemic doxycycline for 8 weeks. This dose level also begins with a sentinel participant and proceeds following DSMB review.

  Genetic: ER-100 epigenetic therapy

• Experimental
  NAION - Selected Dose ER-100

  Participants with Non-Arteritic Anterior Ischemic Optic Neuropathy will receive ER-100 at a dose selected based on safety and tolerability data from the OAG cohort. ER-100 is administered to one eye and activated by systemic doxycycline for 8 weeks. Initial enrollment is limited to three participants, with potential expansion to six following DSMB review.

  Genetic: ER-100 epigenetic therapy

Interventions

• GeneticER-100 epigenetic therapy

  ER-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.

  Also known as: OSK epigenetic therapy, Investigational epigenetic therapy for optic neuropathies

Primary outcomes

1. 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.

   Time frame: Baseline to Day 56, Day 112

2. 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.

   Time frame: Baseline to Day 56, Day 112

3. 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)

   Time frame: Baseline to Day 56, Day 112

4. 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)

   Time frame: Baseline to Day 56, Day 112

5. Change in Safety Laboratory Tests (Calcium, Glucose, Bilirubin, Creatinine, Blood Urea Nitrogen) During and Post-Doxycycline Activation Period

   These tests show how the body manages minerals, sugar, and waste. Calcium helps with bone and muscle function. Glucose shows blood sugar control. Bilirubin shows liver health. Creatinine and blood urea nitrogen (BUN) show kidney function. Compared to baseline, higher or lower levels can mean problems with the liver, kidneys, or metabolism. Unit of Measure: Milligrams per deciliter (mg/dL)

   Time frame: Baseline to Day 56, Day 112

6. Change in Safety Laboratory Tests (Electrolytes: Sodium, Potassium, Chloride) During and Post-Doxycycline Activation Period

   Electrolytes help keep the body's fluids and nerves working properly. Changes can mean dehydration or kidney problems. This outcome looks at how much sodium (Na), potassium (K), and chloride (Cl) levels change from baseline. Unit of Measure: Millimoles per liter (mmol/L)

   Time frame: Baseline to Day 56, Day 112

7. Change in Safety Laboratory Tests (Electrolytes: Bicarbonate and Magnesium) During and Post-Doxycycline Activation Period

   Bicarbonate helps control the body's acid balance. Magnesium is important for muscles and nerves. Changes can mean metabolic or kidney problems. This outcome looks at how much these levels change from baseline. Unit of Measure: Milliequivalents per liter (mEq/L)

   Time frame: Baseline to Day 56, Day 112

8. Change in Safety Laboratory Tests (Hemoglobin) During and Post-Doxycycline Activation Period

   Hemoglobin is a protein in red blood cells that carries oxygen. Lower levels can mean anemia, which is when the blood cannot carry enough oxygen. This outcome looks at how much hemoglobin changes from baseline. Unit of Measure: Grams per deciliter (g/dL)

   Time frame: Baseline to Day 56, Day 112

9. Change in Safety Laboratory Tests (Hematocrit) During and Post-Doxycycline Activation Period

   Hematocrit shows the percentage of blood made up of red blood cells. Compared to baseline, lower levels can mean anemia, which is when the blood cannot carry enough oxygen. Unit of Measure: Percent (%)

   Time frame: Baseline to Day 56, Day 112

10. Change in Safety Laboratory Tests (White Blood Cell and Platelet Counts) During and Post-Doxycycline Activation Period

    White blood cells help fight infection. Platelets help blood clot. Compared to baseline, changes can mean infection, immune problems, or bleeding risk. Unit of Measure: Billion cells per liter (x10\^9/L)

    Time frame: Baseline to Day 56, Day 112

11. Change in Safety Laboratory Tests (Red Blood Cell Count) During and Post-Doxycycline Activation Period

    Red blood cells carry oxygen throughout the body. Compared to baseline, lower levels can mean anemia, which is when the blood cannot carry enough oxygen. Unit of Measure: Trillion cells per liter (x10\^12/L)

    Time frame: Baseline to Day 56, Day 112

12. Change in Safety Laboratory Tests (Erythrocyte Sedimentation Rate) During and Post-Doxycycline Activation Period

    This test shows inflammation in the body. Compared to baseline, higher values can mean infection or other inflammatory conditions. Unit of Measure: Millimeters per hour (mm/hr)

    Time frame: Baseline to Day 56, Day 112

13. Change in Safety Laboratory Tests (C-Reactive Protein) During and Post-Doxycycline Activation Period

    C-reactive protein shows inflammation in the body. Compared to baseline, higher values can mean infection or other inflammatory conditions. Unit of Measure: Milligrams per liter (mg/L)

    Time frame: Baseline to Day 56, Day 112

14. Change in Safety Laboratory Tests (Urine Test Results) During and Post-Doxycycline Activation Period

    Urine tests check for blood, protein, sugar, and other substances. Compared to baseline, changes can mean kidney or urinary tract problems. Unit of Measure: Presence or absence

    Time frame: Baseline to Day 56, Day 112

15. Change from Baseline in the Intraocular Pressure (IOP) in the Treated Eye During and Post-Doxycycline Activation Period - Safety

    This outcome measures changes 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. Depending on their values, higher or lower pressures compared to the participant's baseline may indicate safety concerns related to the treatment.

    Time frame: Baseline to Day 56, Day 112

16. Change from Baseline in the Best Corrected Visual Acuity (BCVA) Letter Score in the Treated Eye During and Post-Doxycycline Activation 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 while participants are receiving and completed 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. A drop in score from the 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.

    Time frame: Baseline to Day 56, Day 112

17. Change from Baseline in Humphrey Visual Field (HVF) Test Results During and Post-Doxycycline Activation Period - Safety

    This outcome measures the change in central and peripheral (side) field of vision while participants are receiving and completed oral doxycycline. The field of vision is assessed using the Humphrey Visual Field (HVF) test, which checks how well a person can see lights that flash in different areas of their visual field while they focus on a central point. Results are reported as a Mean Deviation (MD) score in decibels (dB). For participants with open-angle glaucoma (OAG), the test uses the SITA Standard 24-2 protocol. For participants with non-arteritic anterior ischemic optic neuropathy (NAION), a larger light stimulus (size V) is used. Compared to baseline, a more negative MD score means more vision loss, and a significant worsening in MD may suggest a safety concern.

    Time frame: Baseline to Day 56, Day 112

18. Change from Baseline in Pattern Electroretinogram (pERG) During and Post-Doxycycline Activation Period - Safety

    This outcome measures the change in retinal function while participants are receiving and completed oral doxycycline. The pERG is a test that checks how well the retina responds to visual patterns like black and white stripes. It helps evaluate the health of retinal ganglion cells, which are important for sending visual signals to the brain. The test provides two types of results: * Amplitude (measured in microvolts, µV): This shows the strength of the retina's response. * Peak time (measured in milliseconds, ms): This shows how quickly the retina responds. Lower amplitudes or slower response times than those recorded at baseline may indicate worsening retinal function. A significant decline in these results may suggest a safety concern related to disease progression or if there are signs that the treatment is causing effects.

    Time frame: Baseline to Day 56, Day 112

19. Change from Baseline in Quantitative Contrast Sensitivity Function (qCSF) During and Post-Doxycycline Activation Period - Safety

    This outcome measures the change in contrast sensitivity while participants are receiving and completed oral doxycycline. The quantitative Contrast Sensitivity Function (qCSF), also called quick CSF, is a computerized test that evaluates how well a person can detect differences in contrast, for example, the ability to discern subtle differences in shading or light and dark between an object and its background. Lower scores than those recorded at baseline may indicate worsening visual function, and a significant decline in one or more parameters may suggest a safety concern. Changes in these scores are monitored to detect potential trea

    Time frame: Baseline to Day 56, Day 112

20. Change from Baseline in Optical Coherence Tomography (OCT): Ganglion Cell Layer (GCL) Thickness During and Post-Doxycycline Activation Period - Safety

    This outcome measures the change in the thickness of the ganglion cell layer (GCL) while participants are receiving and completed oral doxycycline. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using an instrument called the Heidelberg Spectralis system. The GCL contains the cell bodies of retinal ganglion cells, which are critical for transmitting visual information from the retina to the brain. GCL thickness is measured in micrometers (µm). A significant decrease in GCL thickness from baseline may suggest a safety concern related to disease progression or if there are signs that the treatment is causing effects.

    Time frame: Baseline to Day 56, Day 112

21. Change from Baseline in Optical Coherence Tomography (OCT): Retinal Nerve Fiber Layer (RNFL) Thickness During and Post-Doxycycline Activation Period - Safety

    This outcome measures the change in the thickness of the retinal nerve fiber layer (RNFL) while participants are receiving and completed oral doxycycline. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using the Heidelberg Spectralis system. The RNFL contains nerve fibers that help carry visual signals from the eye to the brain. RNFL thickness is measured in micrometers (µm). A significant decrease in RNFL thickness from baseline may suggest a safety concern related to disease progression or if there are signs that the treatment is causing effects.

    Time frame: Baseline to Day 56, Day 112

22. Change from Baseline in Slit Lamp Exam Results During and Post-Doxycycline Activation Period - Safety

    This outcome measures changes in the health of the front structures of the eye while participants are receiving and completed oral doxycycline. A slit lamp exam is a routine eye test that uses a bright light and microscope to closely examine the front parts of the eye, including the cornea, iris, lens, and the white part of the eye. The exam helps detect signs of irritation, inflammation, infection, or other possible damage. Changes from baseline observed during the slit lamp exam might be signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Day 56, Day 112

Secondary outcomes

1. 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.

   Time frame: Baseline to Day 56, Day 112

2. 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.

   Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

3. 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.

   Time frame: Baseline to Day 56, Day 112

4. 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.

   Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

5. Change from Baseline in Humphrey Visual Field (HVF) Test Results During and Post-Doxycycline Activation Period - Efficacy

   This outcome measures the change in central and peripheral (side) field of vision while participants are receiving and completed oral doxycycline. The field of vision is assessed using the Humphrey Visual Field (HVF) test, which checks how well a person can see lights that flash in different areas of their visual field while they focus on a central point. Results are reported as a Mean Deviation (MD) score in decibels (dB). For participants with open-angle glaucoma (OAG), the test uses the SITA Standard 24-2 protocol. For participants with non-arteritic anterior ischemic optic neuropathy (NAION), a larger light stimulus (size V) is used. Compared to baseline, a more negative MD score means more vision loss, while scores closer to zero suggest better or more normal vision. Improvements in MD from baseline may suggest a positive effect of the treatment.

   Time frame: Baseline to Day 56, Day 112

6. Change from Baseline in Humphrey Visual Field (HVF) Test Results - Long-term Follow-up Period - Safety

   This outcome measures the change in peripheral (side) field of vision after participants stop taking oral doxycycline during the long-term follow-up period. Peripheral field of vision vision is assessed using the Humphrey Visual Field (HVF) test, which checks how well a person can see lights that flash in different areas of their visual field while they focus on a central point. Results are reported as a Mean Deviation (MD) score in decibels (dB). For participants with open-angle glaucoma (OAG), the test uses the SITA Standard 24-2 protocol.For participants with non-arteritic anterior ischemic optic neuropathy (NAION), a larger light stimulus (size V) is used. A more negative MD score comparing to baseline means more vision loss, and a significant worsening in MD may suggest a safety concern.

   Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

7. Change from Baseline in Quantitative Contrast Sensitivity Function (qCSF) During and Post-Doxycycline Activation Period - Efficacy

   This outcome measures the change in contrast sensitivity while participants are receiving and completed oral doxycycline. The quantitative Contrast Sensitivity Function (qCSF), also called quick CSF, is a computerized test that evaluates how well a person can detect differences in contrast - for example, the ability to discern subtle differences in shading or light and dark between an object and its background. Higher scores suggest better visual function, while lower scores may indicate difficulty seeing in low-contrast or low-light conditions. Changes in these scores from baseline may reflect signs that the treatment is causing effects.

   Time frame: Baseline to Day 56, Day 112

8. Change from Baseline in Quantitative Contrast Sensitivity Function (qCSF) - Long-term Follow-up Period - Safety

   This outcome measures the change in contrast sensitivity after participants stop taking oral doxycycline during the long-term follow-up period. The quantitative Contrast Sensitivity Function (qCSF), also called quick CSF, is a computerized test that evaluates how well a person can detect differences in contrast - for example, for example, the ability to discern subtle differences in shading or light and dark between an object and its background. Lower scores than the baseline values may indicate worsening visual function, and a significant decline in one or more parameters may suggest a safety concern. Changes in these scores from baseline are monitored to see if there are signs that the treatment is causing effects or that the disease is getting worse.

   Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

9. Change from Baseline in Pattern Electroretinogram (pERG) During and Post-Doxycycline Activation Period - Efficacy

   This outcome measures the change in retinal function while participants are receiving and completed oral doxycycline. The pERG is a test that checks how well the retina responds to visual patterns like black and white stripes. It helps evaluate the health of retinal ganglion cells, which are important for sending visual signals to the brain. The test provides two types of results: * Amplitude (measured in microvolts, µV): This shows the strength of the retina's response. * Peak time (measured in milliseconds, ms): This shows how quickly the retina responds. Higher numbers mean the retina is responding well. Lower numbers or slower response times may suggest that the retina is not working as well as it should. Changes in these results from baseline values may show whether the condition is improving or getting worse during treatment.

   Time frame: Baseline to Day 56, Day 112

10. Change from Baseline in Pattern Electroretinogram (pERG) - Long-term Follow-up Period - Safety

    This outcome measures the change in retinal function after participants stop taking oral doxycycline during the long-term follow-up period. The pERG is a test that checks how well the retina responds to visual patterns like black and white stripes. It helps evaluate the health of retinal ganglion cells, which are important for sending visual signals to the brain. The test provides two types of results: * Amplitude (measured in microvolts, µV): This shows the strength of the retina's response. * Peak time (measured in milliseconds, ms): This shows how quickly the retina responds. Lower amplitudes or slower response times than baseline values may indicate worsening retinal function. A significant decline in these results may suggest a safety concern related to signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

11. Change from Baseline in Optical Coherence Tomography (OCT): Ganglion Cell Layer (GCL) Thickness During and Post-Doxycycline Activation Period - Efficacy

    This outcome measures the change in the thickness of the ganglion cell layer (GCL) while participants are receiving and completed oral doxycycline. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using the Heidelberg Spectralis system. The GCL contains the cell bodies of retinal ganglion cells, which are critical for transmitting visual information from the retina to the brain. GCL thickness is measured in micrometers (µm). Changes in GCL thickness from baseline values may reflect there are signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Day 56, Day 112

12. Change from Baseline in Optical Coherence Tomography (OCT): Ganglion Cell Layer (GCL) Thickness - Long-term Follow-up Period - Safety

    This outcome measures the change in the thickness of the ganglion cell layer (GCL) after participants stop taking oral doxycycline during the long-term follow-up period. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using the Heidelberg Spectralis system. The GCL contains the cell bodies of retinal ganglion cells, which are critical for transmitting visual information from the retina to the brain. GCL thickness is measured in micrometers (µm). A significant decrease in GCL thickness from baseline values may suggest a safety concern related to signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

13. Change from Baseline in Optical Coherence Tomography (OCT): Retinal Nerve Fiber Layer (RNFL) Thickness During and Post-Doxycycline Activation Period - Efficacy

    This outcome measures the change in the thickness of the retinal nerve fiber layer (RNFL) while participants are receiving and completed oral doxycycline. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using the Heidelberg Spectralis system. The RNFL contains nerve fibers that help carry visual signals from the eye to the brain. RNFL thickness is measured in micrometers (µm). Changes in RNFL thickness from baseline values may reflect signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Day 56, Day 112

14. Change from Baseline in Optical Coherence Tomography (OCT): Retinal Nerve Fiber Layer (RNFL) Thickness - Long-term Follow-up Period - Safety

    This outcome measures the change in the thickness of the retinal nerve fiber layer (RNFL) after participants stop taking oral doxycycline during the long-term follow-up period. Optical Coherence Tomography (OCT) is a non-invasive imaging test that uses light waves to take detailed cross-sectional pictures of the retina. OCT will be conducted using the Heidelberg Spectralis system. The RNFL contains nerve fibers that help carry visual signals from the eye to the brain. RNFL thickness is measured in micrometers (µm). A significant decrease in RNFL thickness from baseline values may suggest a safety concern related to signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

15. Change in Neutralizing Antibodies (NAbs) to AAV2 During and Post-Doxycycline Activation Period

    This outcome measures changes in the body's immune response to the AAV2 virus while participants are receiving and completed oral doxycycline. Specifically, it looks at neutralizing antibodies, which are proteins made by the immune system that can block the virus from working. Blood samples are tested to see how much antibody is present. The results are reported as a number called a "titer," which shows how strong the response is. * A higher titer means the body is making more antibodies that can block the virus. * A lower titer or no detectable antibodies means the virus is less likely to be blocked. These results help researchers understand how the body reacts to the treatment and whether the immune system might affect how well the therapy works.

    Time frame: Baseline to Day 56, Day 112

16. Change in Cellular Immune Response to ER-100 Peptides via ELISpot During and Post-Doxycycline Activation Period

    This outcome measures how the immune system's T cells respond to parts of the ER-100 treatment while participants are receiving and completed oral doxycycline. A lab test called ELISpot is used to count how many immune cells release a signal when they recognize parts of the treatment. Each signal shows up as a spot in the test - more spots mean a stronger immune response, and fewer spots mean a weaker response. This helps researchers understand how active the immune system is and whether it might affect how well the treatment works or how the body tolerates it.

    Time frame: Baseline to Day 56, Day 112

17. Change in ER-100 Viral Shedding via qPCR to During and Post-Doxycycline Activation Period

    This outcome measures whether any part of the ER-100 treatment is released from the body while participants are receiving and completed oral doxycycline. Samples are collected from tears, nasal swab, saliva, blood, urine, and feces. A lab test called qPCR is used to detect tiny amounts of ER-100 DNA in these fluids. If ER-100 DNA is found, it means the treatment is leaving the body through these fluids - this is called viral shedding. If no ER-100 DNA is found, it means the treatment is staying inside the body. More shedding may suggest the body is clearing the treatment faster, while less or no shedding may mean the treatment is staying localized or being retained longer. This helps researchers understand how the treatment moves through the body and whether it could be passed to others.

    Time frame: Baseline to Day 56, Day 112

18. Change in Biodistribution of ER-100 Vector DNA in Aqueous Humor During Doxycycline Activation Period

    This outcome measures whether any part of the ER-100 treatment is found in the fluid inside the eye (called aqueous humor) while participants are receiving oral doxycycline. This test is only done in participants with open-angle glaucoma (OAG). A lab test called qPCR is used to detect tiny amounts of ER-100 DNA in the eye fluid. * If ER-100 DNA is found, it means the treatment has reached the inside of the eye. * If no ER-100 DNA is found, it means the treatment has not entered that part of the eye. This helps researchers understand where the treatment travels in the body and whether it stays in the intended area.

    Time frame: Baseline to Day 56

19. Change from Baseline in Slit Lamp Exam Results - Long-term Follow-up Period - Safety

    This outcome measures changes in the health of the front structures of the eye after participants stop taking oral doxycycline during the long-term follow-up period. A slit lamp exam is a routine eye test that uses a bright light and microscope to closely examine the front parts of the eye, including the cornea, iris, lens, and the white part of the eye. The exam helps detect signs of irritation, inflammation, infection, or other damage. Changes from baseline observed during the slit lamp exam might be signs that the treatment is causing effects or that the disease is getting worse.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

20. Incidence of Treatment-Emergent Adverse Events (TEAEs) - Long-term Follow-up Period

    This outcome tracks any new or worsening health problems that occur after participants stop taking oral doxycycline during the long-term follow-up period. These health problems are called treatment-emergent adverse events (TEAEs). Researchers record how often these events happen, what kind they are (such as headaches, infections, or changes in lab tests), and how serious they are. This helps determine whether the ER-100 treatment causes any long-term side effects or health concerns, even months or years after the initial treatment.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

21. Change in Safety Laboratory Test Results - Long-term Follow-up Period

    This outcome measures changes in routine lab test results after participants stop taking oral doxycycline, during the long-term follow-up period. These tests check things like liver and kidney function, blood counts, and other indicators of general health. If lab values change over time, it may show how the body is responding to the ER-100 treatment in the long term. This helps researchers monitor for any delayed side effects or health concerns.

    Time frame: Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

Individual participant data

Plan to share: Undecided — The decision to share individual participant data (IPD) has not yet been finalized. Data sharing may be considered after study completion, depending on regulatory guidance, publication requirements, and available resources to support secure access.