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

December 22, 2025 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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

70

Phase

  • 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 Contact

Study Locations

  • Italy
    • Brescia
      • Brescia, Brescia, Italy, 25123
        • Recruiting
        • Università di Brescia
    • Firenze
      • Florence, Firenze, Italy, 50134
        • Recruiting
        • Azienda Ospedaliero Universitaria Careggi
  • Poland
    • Silesian Voivodeship
      • Katowice, Silesian Voivodeship, Poland, 40-594
        • Recruiting
        • Gabinet Okulistyczny Prof Edward Wylegala
  • Spain
    • Barcelona
      • Barcelona, Barcelona, Spain, 08035
        • Recruiting
        • IMO Barcelona, Grupo Miranza
    • Córdoba
      • Córdoba, Córdoba, Spain, 14012
        • Recruiting
        • Hospital La Arruzafa
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33012
        • Recruiting
        • Instituto Oftalmologico Fernandez-Vega
    • Valencia
      • Valencia, Valencia, Spain, 46004
        • Recruiting
        • Aiken Prevención & Cirugía Ocular
  • United States
    • California
      • Laguna Hills, California, United States, 92653
        • Recruiting
        • Harvard Eye Associates
        • Principal Investigator:
          • John Hovanesian, M.D.
        • Contact:
      • Loma Linda, California, United States, 92354
        • Recruiting
        • Loma Linda University Eye Institute
        • Contact:
        • Principal Investigator:
          • John Affeldt, M.D.
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Active, not recruiting
        • Retina Consultants of Southern Colorado
      • Longmont, Colorado, United States, 80503
        • Recruiting
        • Advance Vision Research Institute
        • Contact:
        • Principal Investigator:
          • Aimee Verner, M.D.
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Recruiting
        • Connecticut Eye Consultants, P.C. Danbury Eye Physicians & Surgeons
        • Contact:
        • Principal Investigator:
          • Matthew Paul, M.D.
    • Florida
      • Crystal River, Florida, United States, 34429
        • Recruiting
        • Nature Coast Clinical Research
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami - Bascom Palmer Eye Institute, Miami
        • Principal Investigator:
          • Jaime Martinez Martinez, M.D.
        • Contact:
      • Tampa, Florida, United States, 33612
        • Recruiting
        • University of South Florida, Ophthalmolgoy
        • Contact:
        • Principal Investigator:
          • Edgar Espana, M.D.
    • Georgia
      • Sandy Springs, Georgia, United States, 30328
        • Recruiting
        • Thomas Eye Group, P.C.
        • Contact:
        • Principal Investigator:
          • David Sackel, M.D.
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Indiana
      • Carmel, Indiana, United States, 46290
        • Recruiting
        • Midwest Cornea Associates, LLC.
        • Contact:
        • Principal Investigator:
          • Jennifer Nottage, M.D.
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • Active, not recruiting
        • Huffman & Huffman, PSC
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Recruiting
        • Midwest Vision Research Foundation
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University Eye Center
        • Contact:
        • Principal Investigator:
          • Jennifer Enright, M.D.
    • New Jersey
      • Palisades Park, New Jersey, United States, 07650
        • Recruiting
        • Metropolitan Eye Research and Surgery Institute
        • Contact:
        • Principal Investigator:
          • David Chu, M.D.
    • New York
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke Eye Center
        • Principal Investigator:
          • Lloyd Williams, M.D.
        • Contact:
      • Raleigh, North Carolina, United States, 27617
        • Active, not recruiting
        • Oculus Research
      • Shelby, North Carolina, United States, 28150
        • Active, not recruiting
        • CORE, Inc. / Vita Eye Clinic
    • Ohio
      • Cleveland, Ohio, United States, 44106
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic, Cole Eye Institute
        • Principal Investigator:
          • Rony Sayegh, M.D.
        • Contact:
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Active, not recruiting
        • Pacific ClearVision Institute
      • Medford, Oregon, United States, 97504
        • Recruiting
        • Cataract & Laser Institute of Southern Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • OHSU Casey Eye Institute
        • Contact:
        • Principal Investigator:
          • Richard Stutzman, M.D.
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • UPMC Eye Center
        • Contact:
        • Principal Investigator:
          • Vishal Jhanji, M.D.
    • Texas
      • San Antonio, Texas, United States, 78240
        • Recruiting
        • MCOA Eye Care
        • Principal Investigator:
          • Anushree Sharma, M.D.
        • Contact:
      • Sugar Land, Texas, United States, 77478
        • Recruiting
        • Berkeley Eye Center
        • Contact:
        • Principal Investigator:
          • J. Morgan Micheletti
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Virginia Eye Consultants
    • Washington
      • Seatle, Washington, United States, 98104
        • Recruiting
        • University of Washington, Department of Ophthalmology
        • Contact:
        • Principal Investigator:
          • Miel Sundararajan, M.D.

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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
Intervention / Treatment
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

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

Outcome Measure
Measure Description
Time Frame
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
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Intraocular Pressure (Unit: mmHg)
Time Frame: Day 1, 8, 29 and 43
Day 1, 8, 29 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

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)

April 11, 2023

Primary Completion (Estimated)

April 30, 2026

Study Completion (Estimated)

May 30, 2026

Study Registration Dates

First Submitted

September 15, 2022

First Submitted That Met QC Criteria

September 22, 2022

First Posted (Actual)

September 27, 2022

Study Record Updates

Last Update Posted (Estimated)

December 23, 2025

Last Update Submitted That Met QC Criteria

December 22, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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

product manufactured in and exported from the U.S.

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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