Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2

November 4, 2026 updated by: ReGenTree, LLC

A Phase 3, Multi-Center, Randomized, Parallel, Double Masked, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy (SEER-2)

The objective of this study is to compare the safety and efficacy of RGN-259 to placebo for the treatment of Neurotrophic Keratopathy (NK)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Neurotrophic keratopathy (NK) is a degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervation. The resulting loss of corneal sensitivity (anesthesia) leads to a reduction in lacrimation and a decline in status, metabolism, and mitosis of corneal epithelial cells.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Brescia
      • Brescia, Brescia, Italy, 25123
        • Università di Brescia
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Azienda Ospedaliero Universitaria Careggi
    • Lombardy
      • Milan, Lombardy, Italy, 20132
        • Ospedale San Raffaele s.r.l.
      • Milan, Lombardy, Italy, 20142
        • Università degli Studi di Milano - ASST Santi Paolo e Carlo
  • Poland
    • Silesian Voivodeship
      • Katowice, Silesian Voivodeship, Poland, 40-594
        • Gabinet Okulistyczny Prof Edward Wylegala
  • Spain
    • Barcelona
      • Barcelona, Barcelona, Spain, 08035
        • IMO Barcelona, Grupo Miranza
    • Córdoba
      • Córdoba, Córdoba, Spain, 14012
        • Hospital La Arruzafa
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33012
        • Instituto Oftalmológico Fernández-Vega
    • Valencia
      • Valencia, Valencia, Spain, 46004
        • Aiken Prevención & Cirugía Ocular
  • United States
    • Alabama
      • Vestavia Hills, Alabama, United States, 35242
        • Parker Cornea
    • California
      • Laguna Hills, California, United States, 92653
        • Harvard Eye Associates
      • Loma Linda, California, United States, 92354
        • Loma Linda University Eye Institute
      • Los Angeles, California, United States, 90013
        • Nvision Clinical Research, LLC
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Retina Consultants of Southern Colorado
      • Longmont, Colorado, United States, 80503
        • Advance Vision Research Institute
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Connecticut Eye Consultants, P.C. Danbury Eye Physicians & Surgeons
    • Florida
      • Crystal River, Florida, United States, 34429
        • Nature Coast Clinical Research
      • Miami, Florida, United States, 33136
        • University of Miami - Bascom Palmer Eye Institute, Miami
      • Tampa, Florida, United States, 33612
        • University of South Florida, Ophthalmolgoy
    • Georgia
      • Sandy Springs, Georgia, United States, 30328
        • Thomas Eye Group, P.C.
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern
    • Indiana
      • Carmel, Indiana, United States, 46290
        • Midwest Cornea Associates, LLC.
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • Huffman & Huffman, PSC
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Wilmer Eye Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Midwest Vision Research Foundation
      • St Louis, Missouri, United States, 63108
        • Washington University Eye Center
    • New Jersey
      • Eatontown, New Jersey, United States, 07724
        • Atlantic Eye
      • Palisades Park, New Jersey, United States, 07650
        • Metropolitan Eye Research and Surgery Institute
    • New York
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Eye Center
      • Raleigh, North Carolina, United States, 27617
        • Oculus Research
      • Shelby, North Carolina, United States, 28150
        • CORE, Inc. / Vita Eye Clinic
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic, Cole Eye Institute
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Pacific ClearVision Institute
      • Medford, Oregon, United States, 97504
        • Cataract & Laser Institute of Southern Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Casey Eye Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Scheie Eye Institute, University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Eye Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Regional Eye Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Eye Institute
    • Texas
      • Dallas, Texas, United States, 75231
        • Cornea Associates of Texas
      • Houston, Texas, United States, 77025
        • Houston Eye Associates
      • Mission, Texas, United States, 78572
        • CliniVerse Research
      • San Antonio, Texas, United States, 78212
        • Stuart Terry Eye Associates
      • San Antonio, Texas, United States, 78240
        • MCOA Eye Care
      • Sugar Land, Texas, United States, 77478
        • Berkeley Eye Center
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Eye Consultants
    • Washington
      • Seattle, Washington, United States, 98104
        • University of Washington, Department of Ophthalmology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Be male or female of any race, at least 18 years of age;
  2. Have provided written informed consent;
  3. Be able and willing to follow instructions, including participation in all study assessments and visits;
  4. At the time of Visit 1, have documentation or observation of a Persistent Epithelial Defect (PED) in one or both eyes, defined as a corneal epithelial defect that has not resolved after 1 week of conventional treatment using non-preserved ocular lubricants, non-preserved topical ophthalmic antibiotics, oral doxycycline, patching, amniotic membrane, serum tears, and/or therapeutic contact lenses;
  5. Have stage 2 or 3 neurotrophic keratopathy (Mackie Classification) in at least one eye of which the longest dimension (length or width) of the defect measures a minimum length of 1 mm (study eye) and which is confirmed by the Investigator not to be simply superficial punctate keratitis, at Visit 1;
  6. Have evidence of decreased corneal sensitivity ≤40 mm using the Cochet-Bonnet aesthesiometer at Visit 1;
  7. Have BCVA score ≤75 letter counts in the study eye based on the ETDRS protocol;
  8. Have at least one eye (the same eye) satisfy all criteria for d, e, f, g above;
  9. Female subjects of child-bearing potential must be non-lactating and using and agree to continue using an acceptable method of contraception for at least 4 weeks prior to the first dose of study product and until 12 weeks after last dose, and have a negative urine pregnancy test during screening;
  10. Male subjects must agree to use an adequate method of contraception.

Exclusion Criteria

  1. Have any condition that, in the opinion of the Investigator, would interfere with the subject's ability to complete the study, would interfere with the interpretation of safety or efficacy, or would present an undue risk to the subject.
  2. Have any clinically significant slit-lamp findings in the study eye that in the opinion of the Investigator may interfere with the study parameters;
  3. Clinically significant active blepharitis, meibomian gland dysfunction (MGD), or lid margin inflammation, or active ocular allergy in study eye that requires treatment that in the opinion of the investigator may interfere with the study parameters;
  4. Have a Unanesthetized Schirmer's test score of ≤3 mm at Visit 1;
  5. Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the Investigator, is the primary cause of the persistent epithelial defect;
  6. Have an ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g., follicular conjunctivitis) in the study eye.
  7. History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrollment.
  8. Prior surgical procedure(s) for the treatment of NK (e.g., tarsorrhaphy, conjunctival flap, etc.) within the three months before study enrollment with the exception of amniotic membrane transplantation.
  9. Have any planned ocular surgical procedures or are likely to require ocular surgery for the study eye during the study;
  10. Have received Botox® injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1;
  11. Have used contact lenses (for therapeutic or refractive correction) in the study eye within 14 days prior to Visit 1, or anticipate use of contact lenses during the study period.
  12. Have used OxervateTM in the study eye within the past 2 months;
  13. Anticipate use of serum tears in the study eye during the study period.
  14. Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the Investigator to be incompatible with the study visit schedule or conduct;
  15. Have used drugs which affect lacrimation or function of the trigeminal nerve within 30 days of Visit 1 or anticipate use of these systemic medication throughout the course of the study;
  16. Have any autoimmune or chronic inflammatory disease that might have hindered the efficacy of the study treatment or its evaluation;
  17. Be on topical (Ocular/Nasal) immunosuppressive therapy within 30 days prior to screening or is likely to require this during the course of the study;
  18. Have a known allergy and/or sensitivity to the study product or its components;
  19. History of drug, medication or alcohol abuse or addiction;
  20. Have participated in an investigational drug study within 30 days prior to screening;
  21. Have fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection, including COVID-19 or a positive test for COVID-19, within 2 weeks prior to first dose of study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 0.1% RGN-259 Opthalmic Solution

It is a preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into study eye(s), five times per day for 28 days
Drug: RGN-259

A preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into study eye(s), five times per day for 28 days

Other Names:
  • Tβ4
  • Thymosin Beta 4
  • Timbetasin
Placebo Comparator: Placebo Ophthalmic Solution (Vehicle for RGN-259 Ophthalmic Solution)

It is composed of the same excipients as RGN-259 but does not contain Tβ4
Drug: Placebo

It is composed of the same excipients as RGN-259 but does not contain Tβ4. Direct instillation into study eye(s), five times per day for 28 days

Other Names:
  • Vehicle Control

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of subjects achieving complete healing of PED at Day 29
Time Frame: Day 29

Percentage of subjects achieving complete healing of the Persistent Epithelial Defect (PED) at Day 29 determined by corneal fluorescein staining as measured by the Central Reading Center.
Day 29

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Corneal sensitivity inside the lesion determined by Cochet Bonnet aesthesiometer (Unit: mm)
Time Frame: Day 8, 15, 22, 29, 36, and 43
Day 8, 15, 22, 29, 36, and 43
Percentage of subjects achieving complete healing of PED at Day 29
Time Frame: Day 29

Percentage of subjects achieving complete healing of the PED determined by corneal fluorescein staining as measured by the Investigator.
Day 29
Percentage change from baseline of lesion size
Time Frame: Day 8, 15, 22, 29, 36, and 43

Percentage change from baseline of lesion size determined by corneal fluorescein staining (measurements of greatest dimension of fluorescein staining)
Day 8, 15, 22, 29, 36, and 43
NK stage by Mackie classification
Time Frame: Day 8, 15, 22, 29, 36, and 43

NK stage graded according to the Mackie classification (Stage I, II, III. Higher scores mean a better or worse outcome)
Day 8, 15, 22, 29, 36, and 43
Visual Acuity determined by ETDRS
Time Frame: Day 8, 15, 22, 29, 36, and 43

Visual Acuity determined by Early Treatment of Diabetic Retinopathy Study (ETDRS)
Day 8, 15, 22, 29, 36, and 43

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Intraocular Pressure (Unit: mmHg)
Time Frame: Day 1, 8, 29 and 43
Day 1, 8, 29 and 43
Frequency and severity of AEs
Time Frame: Day 8, 15, 22, 29, 36, and 43

Frequency and severity of AEs as reported according to the NCI CTCAE version 5.0
Day 8, 15, 22, 29, 36, and 43
Number of participants with abnormal vital signs
Time Frame: Day 1, 8, 15, 22, 29, 36, and 43

Blood pressure, heart rate, respiratory rate, oxygen saturation, and body temperature will be measured and assessed its clinical abnormality.
Day 1, 8, 15, 22, 29, 36, and 43
Dilated fundoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve)
Time Frame: Day 1, 8, 29 and 43

The fundoscopy exam will be performed and clinical abnormality of vitreous, retina, Macula, Choroid and Optic Nerve will be described.
Day 1, 8, 29 and 43
Slit-lamp biomicroscopy (Cornea, Conjunctiva, Anterior Chamber, Iris, Lens, Lid)
Time Frame: Day 1, 8, 15, 22, 29, 36, and 43

The Slit-Lamp biomicroscopy will be performed and clinical abnormality of Cornea, Conjunctiva, Anterior Chamber, Iris, Lens and Lid will be described.
Day 1, 8, 15, 22, 29, 36, and 43

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ReGenTree, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 11, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 28, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 28, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 15, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 22, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RGN-NK-302

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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