ER-100 treatment for open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy

A Phase 1 Single Dose Study to Evaluate the Safety and Tolerability of ER-100 in Optic Neuropathies [Open Angle Glaucoma (OAG) and Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)]

This trial will test a single dose of ER-100 gene therapy in adults with open-angle glaucoma or NAION to see if it is safe and what side effects occur.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 40 Years to 85 Years
• Sex: All
• Sponsor: Life Biosciences Inc. (Industry-sponsored)
• Locations: 4 sites (Glendale, California and 3 other locations)
• Trial ID: NCT07290244 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1 trial gives a single dose of ER-100, an AAV-based delivery of OSK proteins, to adults with open-angle glaucoma or NAION to test safety and tolerability. Systemic doxycycline is given for eight weeks to activate OSK expression and participants undergo detailed eye exams, laboratory testing, and body fluid sampling (tears, saliva, feces, urine). The study enrolls a dose-escalation cohort in OAG followed by a dose-expansion cohort in NAION and includes patient-reported quality-of-life questionnaires. Participants are followed for up to five years to monitor short- and long-term safety and vision outcomes.

Who should consider this trial

Good fit: Adults aged 40–85 with documented open-angle glaucoma with moderate-to-advanced visual field loss or with NAION, who can have pupil dilation, follow study visits and procedures, and comply with contraception requirements are the intended candidates.

Not a fit: People with mild disease, uncontrolled intraocular pressure, recent or planned eye surgery, inability to have pupils dilated, or who cannot comply with follow-up and contraception requirements are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, ER-100 could slow or reverse cellular aging in retinal cells and help protect or improve vision in people with OAG or NAION.

How similar studies have performed: Epigenetic reprogramming approaches delivering OSK have shown promising results in animal models, but this is the first human trial of an OSK-delivering AAV therapy for optic neuropathies.

Eligibility criteria

Inclusion Criteria:

* 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).
* If only one eye is affected, there must be a difference in pupil response between the two eyes.
* Have vision in the affected eye between 20/40 and 2/500 on a standard eye chart.

Exclusion Criteria:

* 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.
* Have previously received any gene therapy using adeno-associated virus (AAV).

Additional Exclusion Criteria for Participants with Open-Angle Glaucoma (OAG):

\- Diagnosed with glaucoma before age 40.

Additional Exclusion Criteria for Participants with NAION:

* Show signs of giant cell arteritis (a type of blood vessel inflammation), based on abnormal blood tests.
* Had NAION start in both eyes at the same time.

Where this trial is running

Glendale, California and 3 other locations

• Global Research Management, Inc. — Glendale, California, United States (Recruiting)
• Mass Eye and Ear — Boston, Massachusetts, United States (Not_yet_recruiting)
• Columbia University Irving Medical Center/Edward S. Harkness Eye Institute — New York, New York, United States (Not_yet_recruiting)
• Charleston Neuroscience Institute — Charleston, South Carolina, United States (Recruiting)

Study contacts

• Study coordinator: Life Biosciences

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