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

NCT ID: NCT07290244

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2032-03-31

Brief Summary

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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

Detailed Description

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This first-in-human (FIH), Phase 1 clinical trial is designed to evaluate the safety and tolerability of ER-100, an investigational epigenetic therapy candidate intended for age-related optic neuropathies, such as Open Angle Glaucoma (OAG) and Non Arteritic Anterior Ischemic Optic Neuropathy(NAION) Over time, factors such as age, disease, injury, and lifestyle can leave marks on cells that affect how genes function. These marks, known as epigenetic changes, may contribute to cellular decline. ER-100 is designed to address cellular aging through epigenetic reprogramming. It works by delivering genetic instructions for producing three proteins-collectively referred to as OSK-that may help reverse these changes and restore cells to a more youthful state.

The therapy deployed in this trial uses a modified adeno-associated virus (AAV) vector to deliver OSK to retinal cells. The AAV has been engineered to remove its ability to cause infectious disease. Systemic doxycycline is administered for 8 weeks (56 days) to activate OSK expression. ER-100 does not alter the participant's existing genes.

The study includes two sequential cohorts: a dose escalation phase in participants with OAG, followed by a dose expansion phase in participants with NAION. In OAG, optic nerve damage is caused by increased intraocular pressure; in NAION, it results from sudden loss of blood flow. Both conditions lead to retinal cell damage and vision loss. ER-100 is intended to reduce this damage by reprogramming affected cells, potentially preserving or restoring vision.

At least two dose levels will be evaluated in the OAG cohort. The first ("sentinel") participant at each new dose level will receive ER-100 and be monitored for 28 days with review of data by a Safety Review Committee (SRC) prior to granting administration of ER-100 to 2 additional participants at that dose level. Dose escalation/reduction will proceed for subsequent participants in accordance with safety data and oversight from the SRC.

Once the dose escalation in OAG is complete, a dose will be selected for NAION after a consultation between the SRC and Sponsor. Initially only up to 3 NAION participants will be enrolled at the selected dose. After at least one NAION participant has completed 28 days of follow-up, the SRC will review safety data. All participants' data available at that time will be provided to the SRC for the review. Upon recommendation from the SRC, NAION enrollment may then continue up to a total of 6 NAION participants.

Up to 18 participants are planned for enrollment: 12 with OAG and 6 with NAION. A total of 14 clinic visits is planned for the study: 9 in the first 6 months, then one visit per year through Year 5. Additionally, there will be approximately 3 remote (telephone) visits.

This study represents the first administration of ER-100 in humans, following preclinical evaluation in laboratory models.

In this study, results are compared to baseline, which refers to assessments and study procedures at the first study visit and prior to ER-100 administration.

Conditions

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

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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 SRC review prior to cohort expansion.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 SRC review.

Group Type EXPERIMENTAL

ER-100 epigenetic therapy

Intervention Type 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.

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 SRC review.

Group Type EXPERIMENTAL

ER-100 epigenetic therapy

Intervention Type 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.

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 SRC review.

Group Type EXPERIMENTAL

ER-100 epigenetic therapy

Intervention Type 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.

Interventions

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ER-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.

Intervention Type GENETIC

Other Intervention Names

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OSK epigenetic therapy Investigational epigenetic therapy for optic neuropathies

Eligibility Criteria

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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).


\- Diagnosed with glaucoma before age 40.


* 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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Life Biosciences Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sharon Rosenzweign-Lipson, PhD

Role: STUDY_CHAIR

Life Biosciences Inc.

Central Contacts

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Anita Treohan

Role: CONTACT

Phone: 617-702-6202

Email: [email protected]

Other Identifiers

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LB100-001

Identifier Type: -

Identifier Source: org_study_id