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

NCT07290244 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LB100-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Open Angle Glaucoma (OAG); NAION( Non-arteritic Anterior Ischemic Optic Neuropathy)

Keywords

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

Outcome Measures

Primary Outcomes (22)

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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 (%)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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)

  Baseline to Day 56, Day 112

• 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

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

• 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.

  Baseline to Day 56, Day 112

Secondary Outcomes (21)

• Change from Baseline in the Intraocular Pressure (IOP) in the Treated Eye During and Post-Doxycycline Activation Period - Efficacy

  Baseline to Day 56, Day 112

• Change from Baseline in the Intraocular Pressure (IOP) in the Treated Eye - Long-term Follow-up Period - Safety

  Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

• Change from Baseline in the Best Corrected Visual Acuity (BCVA) Letter Score in the Treated Eye During and Post-Doxycycline Activation Period - Efficacy

  Baseline to Day 56, Day 112

• Change from Baseline in the Best Corrected Visual Acuity (BCVA) Letter Score in the Treated Eye - Long-term Follow-up Period - Safety

  Baseline to Month 6, Year 1, Year 2, Year 3, Year 4, Year 5

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

  Baseline to Day 56, Day 112

Study Arms (3)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

NAION - Selected Dose ER-100

EXPERIMENTAL

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

ER-100 epigenetic therapy GENETIC

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

NAION - Selected Dose ER-100; OAG - High Dose ER-100 (6 x 10^11 vg/eye); OAG - Low Dose ER-100 (2 x 10^11 vg/eye)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• If a participant can become pregnant, must agree to use a condom and one highly effective form of birth control during sex for at least 4 months after receiving the study drug (ER-100).
• For participants with open-angle glaucoma (OAG):
• Diagnosis of open-angle glaucoma in the study eye.
• Eye pressure must be less than 30 mmHg, measured with a standard test.
• Visual field test must show moderate to advanced vision loss (MD score between -6 and -20 dB).
• Not expected to need glaucoma surgery in the study eye within 2 months after receiving ER-100.
• Have reasonably good vision in the study eye (at least 20/80 on a standard eye chart).
• For participants with NAION (non-arteritic anterior ischemic optic neuropathy):
• Had a sudden, painless loss of vision in one eye within 14 days before receiving ER-100, confirmed by a specialist. Having had NAION in the other eye is okay.
• The affected eye must show swelling of the optic nerve.
• Visual field test must show vision loss consistent with optic nerve damage (MD worse than -3.0 dB).

You may not qualify if:

• 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.
• Had cataract surgery or other eye surgery (including laser procedures) within 3 months before receiving the study drug.
• Had cancer (except for basal cell skin cancer) within the past 5 years.
• Have Type 1 diabetes, or poorly controlled Type 2 diabetes (A1c greater than 7 despite treatment).
• Have memory or thinking problems that prevent you from understanding the study or completing the required tests.
• Pregnant or breastfeeding.
• Have a weakened immune system, including a history of organ transplant, or test positive for HIV, hepatitis B or C, or tuberculosis.
• Have any other condition that, in the opinion of the study doctor, could increase your risk from the study drug or procedures, affect the study results, or make it hard for you to complete the study.
• Have macular disease, advanced diabetic eye disease, or other eye conditions that limit vision in the study eye.
• Eye pressure at screening is 30 mmHg or higher.
• Taking certain medications (warfarin, dilantin, carbamazepine, or barbiturates) within 14 days before starting the study or during the first 8 weeks.
• Have any other eye or vision problem that, in the opinion of the study doctor, could affect safety or interfere with vision testing.

Sponsors & Collaborators

• Life Biosciences Inc.: lead

Study Sites (4)

Global Research Management, Inc.

Glendale, California, 91204, United States

RECRUITING

Mass Eye and Ear

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Columbia University Irving Medical Center/Edward S. Harkness Eye Institute

New York, New York, 10032, United States

NOT YET RECRUITING

Charleston Neuroscience Institute

Charleston, South Carolina, 29414, United States

RECRUITING

MeSH Terms

Conditions

Glaucoma, Open-Angle; Optic Nerve Diseases; Retinal Diseases

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases; Cranial Nerve Diseases; Nervous System Diseases

Study Officials

• Sharon Rosenzweig-Lipson, PhD

  Life Biosciences Inc.

  STUDY CHAIR

Central Study Contacts

Life Biosciences

CONTACT

(857) 400-9245; ER100trial@lifebiosciences.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study uses a sequential cohort design. Participants with Open Angle Glaucoma (OAG) are enrolled first in a dose escalation phase to evaluate safety and tolerability at multiple dose levels. Each dose level begins with a sentinel participant followed by additional participants after Safety Review Committee (SRC) evaluation. Upon completion of the OAG cohort, a dose is selected for the Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) cohort. NAION participants are enrolled in a dose expansion phase, beginning with limited enrollment and DSMB review prior to cohort expansion.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 18, 2025
• Study Start: March 2, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): March 1, 2032
• Last Updated: May 1, 2026

Record last verified: 2026-03

Locations

US (4)