Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy : SEER-1

Phase 3, Multi-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy: SEER-1

The objective of this study is to assess the safety and efficacy of RGN-259 Ophthalmic Solution compared to placebo for the treatment of NK.

Study Overview

• Status: Terminated
• Conditions: Neurotrophic Keratopathy
• Intervention / Treatment: Drug: Placebo; Drug: RGN-259

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. Previous studies (physician-sponsored studies) used to treat to nine patients with NK, six of whom had discrete geographic, non-healing lesions, and three of whom had punctate lesions and the study result reported.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Lancaster, California, United States, 93534
      • Hull Eye Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Vision Institute
    • Fort Collins, Colorado, United States, 80525
      • Eye Center of Northern Colorado
    • Parker, Colorado, United States, 80134
      • Insight Vision Group
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Medical Faculty Associates, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Cornea Associates, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Koffler Vision Group
    • Louisville, Kentucky, United States, 40206
      • The Eye Care Institute
    • Louisville, Kentucky, United States, 40205
      • Richard Eiferman, MD, PSC
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Eye Care
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be male or female of any race, at least 18 years of age
• Have provided verbal and written informed consent.
• Be able and willing to follow instructions, including participation in all study assessments and visits;
• Have stage 2 or 3 neurotrophic keratopathy in at least one eye If a female of childbearing potential, have a negative urine pregnancy test at Visit 1 and agree to use an adequate method of birth control throughout the study period.

Exclusion Criteria:

• Have any clinically significant slit lamp findings at Visit 1 that in the opinion of the investigator may interfere with the study parameters;
• Have significant blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergy that requires treatment
• Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the investigator, is the primary cause of the persistent epithelial defect;
• Be diagnosed with ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g. follicular conjunctivitis) not related to NK
• Anticipate the use of fluoroquinolone-containing antibiotic eye drops during the study;
• Have used contact lenses (excluding therapeutic contact lenses) within 14 days prior to Visit 1 or anticipates use of contact lenses during the study period;
• Have an uncontrolled systemic disease that in the opinion of the investigator may interfere with the study parameters;
• Anticipate a change in immunosuppressive therapy during the course of the study;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RGN-259; It is a preservative-free, sterile eye drop solution containing Tβ4	Drug: RGN-259; A preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into affected eye(s), five times a day for 4 weeks.; Other Names: Tβ4
Placebo Comparator: Placebo; 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; Other Names: Vehicle Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Complete Healing at Day 29.	Percentage of subjects achieving complete healing of the persistent epithelial defect as determined by corneal fluorescein staining at day 29 after first dosing.	29 days after first dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Achieving Complete Healing at 8, 15, 22, 36, 43 Days	Percentage of subjects achieving complete healing of the Persistent Epithelial Defect(PED) determined by corneal fluorescein staining at 8, 15, 22, 36, 43 days after first dosing.	8, 15, 22, 36, 43 days after first dosing
Epithelial Defect Measurement and Classification as Stage 1, 2 or 3 Using Mackie Classification.	Epithelial Defect Measurement and Classification as stage 1, 2 or 3 using Mackie Classification at 8, 15, 22, 29, 36, 43 days after first dosing	8, 15, 22, 29, 36, 43 days after first dosing
Tear Film Break-up Time at 29, 36, 43 Days	Tear Film Break-up Time at 29, 36, 43 days after first dosing	29, 36, 43 days after first dosing
Ocular Discomfort by Questionnaire at 8, 15, 22, 29, 36, 43 Days After First Dosing	Ocular Discomfort by Questionnaire at 8, 15, 22, 29, 36, 43 Days After First Dosing at Visits 2, 3, 4, 5, 6, and 7 (The scale used to determine the difference in Ocular Discomfort by questionnaire on each visit is from 0(None) to 5(Most). This outcome was calculated from two time points as the value at the later time point minus the value at the first dosing points and the lower value are considered to be a better outcome. and the all relevant time points used in the calculation in the Time Frame was 8, 15, 22, 29, 36, 43 days.)	8, 15, 22, 29, 36, 43 days after first dosing
Visual Acuity(logMAR) at 8, 15, 22, 29, 36, 43 Days	Visual acuity(logMAR) at 8, 15, 22, 29, 36, 43 days (The Visual acuity was assessed by LogMAR calculation method. In the case of the LogMAR method, Each letter has a score value of 0.02 log units. Since there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units. and The lower value are considered to be a better outcome.) The formula used in calculating the score is: LogMAR VA = 0.1 + LogMAR value of the best line read - 0.02 X (number of optotypes read) used to determine the difference in Ocular Discomfort by questionnaire on each visit is the ORA scale: 0 None to 5: Most And as this outcome was calculated from two time points as the value at the later time point minus the value at the first dosing points, The lower value are considered to be a better outcome. and the all relevant time points used in the calculation in the Time Frame was 8, 15, 22, 29, 36, 43 days.)	8, 15, 22, 29, 36, 43 days after first dosing

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants With an Abnormal Findings by Slit-lamp Biomicroscopy at 8, 15, 22, 29, 36, 43 Days	The number of participants with a abnormal findings by Slit-lamp biomicroscopy at 8, 15, 22, 29, 36, 43 days This outcome was assessed by the number of participants with an abnormal findings which are clinically significant using slit-lamp biomicroscopy which provides a magnified view of intraocular structures in the Cornea, Conjunctiva, Anterior Chamber, Iris, Lens, Eyelid.	8, 15, 22, 29, 36, 43 days after first dosing
Corneal Sensitivity Using the Aesthesiometer (Cochet-Bonnet)	Corneal Sensitivity using the aesthesiometer (Cochet-Bonnet) at 29, 43 days after first dosing	29, 43 days after first dosing
The Number of Participants With an Abnormal Findings by Dilated Fundoscopy at 29, 43 Days	The number of participants with an abnormal findings by Dilated Fundoscopy at 29, 43 days This outcome was assessed by the number of participants with an abnormal findings which are clinically significant using Dilated Fundoscopy which is a diagnostic procedure to view the eye's interior, allowing assessment of the Vitreous, Retina, Macula, Choroid, and Optic Nerve.	29, 43 days after first dosing
Intraocular Pressure	Intraocular Pressure at 29, 43 days after first dosing	29, 43 days after first dosing

Collaborators and Investigators

• Sponsor: ReGenTree, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2015
• Primary Completion (Actual): November 20, 2019
• Study Completion (Actual): March 9, 2020

Study Registration Dates

• First Submitted: October 26, 2015
• First Submitted That Met QC Criteria: November 6, 2015
• First Posted (Estimated): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: NK; Neurotrophic Keratopathy
• Other Study ID Numbers: RGN-NK-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO