Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3 (ARISE-3)

A Multi-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of RGN-259 Ophthalmic Solutions for the Treatment of Dry Eye (ARISE-3)

The objective of this study is to compare the safety and efficacy of RGN-259 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye.

Study Overview

• Status: Completed
• Conditions: Dry Eye; Dry Eye Syndromes
• Intervention / Treatment: Drug: RGN-259; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Cornea and Cataract Consultants of Arizona
  • California
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Vision Institute
  • Illinois
    • Chicago, Illinois, United States, 60619
      • Dovilan Wyatt MD, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46240
      • Whitson Vision
    • Indianapolis, Indiana, United States, 46290
      • Midwest Cornea Associates, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • The Eye Care Institute
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Andover Eye Associates
    • Raynham, Massachusetts, United States, 02767
      • Andover Eye Associates
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Center for Sight
  • North Carolina
    • Raleigh, North Carolina, United States, 27603
      • Oculus Research, Inc. at the Eye Care Center
    • Shelby, North Carolina, United States, 28150
      • Visual Eyes Optometric
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Bergstrom Eye Research, LLC
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott & Christie and Associates, PC
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Andover Eye Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, P.A.
  • Texas
    • Austin, Texas, United States, 78731
      • Texan Eye/Keystone Research
  • Utah
    • Layton, Utah, United States, 84041
      • Mountain View Eye Center
    • Ogden, Utah, United States, 84403
      • Country Hills Eye Center
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be at least 18 years of age;
• Provide written informed consent;
• Have a subject reported history of dry eye prior to Visit 1;
• Have a history of use or desire to use eye drops for dry eye symptoms

Exclusion Criteria:

• Have any clinically significant slit-lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters;
• Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
• Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study;
• Have used any eye drops within 2 hours of Visit 1;
• Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 6 months;
• Have used Restasis®, Xiidra® Cequa®, or TrueTear® within 45 days of Visit 1 or Lipiflow® within 6 months of Visit 1;
• Have an intraocular pressure (IOP) > 25 mmHg at Visit 1;
• Have any planned ocular and/or lid surgeries over the study period;
• Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;
• Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study);
• Have corrected visual acuity greater than or equal to logarithm of the minimum angle of resolution (logMAR) +0.7 as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at Visit 1;
• Have an uncontrolled systemic disease;
• Be a woman who is pregnant, nursing or planning a pregnancy;
• Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 4 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (e.g., has had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy), or is post-menopausal (without menses for 12 consecutive months);
• Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; intrauterine device (IUD); or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use adequate birth control as defined above for the remainder of the study;
• Have a known allergy and/or sensitivity to the study drug or its components;
• Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study;
• Have used an investigational drug or device within 30 days of Visit 1;
• Be currently using any medication known to cause ocular drying (e.g., antihistamines, anti-depressants) or increased lacrimation (e.g., cholinergics) that is not used on a stable dosing regimen for at least 30 days prior to Visit 1;
• Be receiving systemic corticosteroid therapy (not including inhaled corticosteroids), ophthalmic topical steroids, topical nonsteroidal antiinflammatory drugs (NSAIDs), topical antibiotics, immunotherapy, or cytotoxic therapy within 14 days of Visit 1 or anticipate such therapy throughout the study period.
• Be unable or unwilling to follow instructions, including participation in all study assessments and visits.

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; RGN-259: It is a preservative-free, sterile eye drop solution containing Thymosin beta 4	Drug: RGN-259; A preservative-free, sterile eye drop solution containing Thymosin beta 4 for direct instillation into each eye, four times a day (QID) for 14 days; Other Names: Tβ4; Thymosin Beta 4
Placebo Comparator: Placebo; It is composed of the same excipients as RGN-259 but does not contain Thymosin beta 4	Drug: Placebo; It is composed of the same excipients as RGN-259 but does not contain Thymosin beta 4; Other Names: Vehicle Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Inferior Corneal Staining Change From Pre-CAE®(Controlled Adverse Environment) to Post-CAE® at Day 15 (Visit 4) Using the Ora Calibra® Scale	Inferior corneal staining was assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 4 scale and where higher numbers indicating more severe staining.	Day 15
Change From Baseline in Ocular Discomfort at Day 15 (Visit 4) Pre-CAE® Using the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire	The severity of ocular discomfort was measured using the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire which is a 0 to 5 scale and where higher numbers indicating more severe discomfort.	Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorescein Staining (Ora Calibra® Scale) at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre and Post-CAE®)	Corneal and conjunctival staining were assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 20 scale and where higher numbers indicating more severe staining.	Day 8, Day 15
Lissamine Green Staining (Ora Calibra® Scale) at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®)	Lissamine green staining were assessed using the Ora Calibra® Corneal and Conjunctival Staining Scale, which is a 0 to 20 scale and where higher numbers indicating more severe staining.	Day 8, Day 15
Tear Film Break-Up Time (TFBUT©) at Visits 3 and 4 (Pre- and Post-CAE®)	TFBUT© measures tear film stability and was assessed by measuring, in seconds, the time from eye opening to the formation of micelles in the tear film. Measurements were obtained using a stopwatch. Longer TFBUT values indicate greater tear film stability and less severe dry eye.	Day 8, Day 15
Unanesthetized Schirmer's Test at Visit 3, Visit 4 (Pre-CAE®)	The Unanesthetized Schirmer's Test measures tear production. A sterile Schirmer test strip was placed in the lower temporal lid margin of each eye, and after 5 minutes, the length of the moistened area on the strip was recorded in millimeters (mm). Higher values indicate greater tear production and a better outcome.	Day 8, Day 15
Drop Comfort Assessment After Randomization at Visit 2	Drop comfort for each eye was assessed using subject-reported drop comfort scale, which is a 0 to 10 scale and where higher numbers indicating more uncomfortable.	Day 1
Ocular Surface Disease Index (OSDI)© at Visits 3 and 4 (Pre-CAE®)	The severity of dry eye disease and its impact on vision-related function were measured using the Ocular Surface Disease Index. Scores range from 0 to 100, with higher scores indicating greater disability.	Day 8, Day 15
Ocular Discomfort & 4-Symptom Questionnaire at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®), Excluding the Hierarchical Efficacy Measure	The severity of 5 symptoms was measured using the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire which is a 0 to 5 scale and where higher numbers indicating more severe discomfort.	Day 8, Day 15
Ocular Discomfort Outside CAE® at Visits 3 and 4 (Change From Pre-CAE® to Post-CAE®, Pre- and Post-CAE®)	Subjects' perceived severity of ocular discomfort was measured using the Ocular Discomfort Scale which is a 0 to 4 scale and where higher numbers indicating more severe discomfort.	Day 8, Day 15
Ocular Discomfort During CAE® at Visit 4	Subjects' perceived severity of ocular discomfort during CAE® exposure was measured using the Ocular Discomfort Scale which is a 0 to 4 scale and where higher numbers indicating more severe discomfort.	Day 15

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity (Using an ETDRS (Early Treatment of Diabetic Retinopathy Study) Chart) at Visits 1, 2, 3 and 4	LogMAR Visual acuity was measured using ETDRS chart at Visits 1, 2, 3 and 4 and represented in LogMAR.	Day -14 ± 1 day, Day 1, Day 8, Day 15
Slit-lamp Biomicroscopy at Visits 1, 2, 3 and 4	Slit-lamp biomicroscopy at Visits 1, 2, 3 and 4	Day -14 ± 1 day, Day 1, Day 8, Day 15
Corneal Sensitivity at Visits 1 and 4 (Pre-CAE®)	Corneal sensitivity was measured using a Cochet-Bonnet esthesiometer by applying gentle pressure to the central corneal surface and recording the filament length (mm) at which the subject perceived the sensation. Higher values (longer filament lengths) indicate greater corneal sensitivity and a better outcome.	Day -14 ± 1 day, Day 15
Undilated Fundoscopy at Visits 1 and 4	Undilated Fundoscopy at Visits 1 and 4	Day -14 ± 1 day, Day 15
Intraocular Pressure at Visits 1 and 4	Intraocular Pressure (mmHg) at Visits 1 and 4	Day -14 ± 1 day, Day 15

Collaborators and Investigators

• Sponsor: ReGenTree, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): November 8, 2020
• Study Completion (Actual): October 7, 2021

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Dry Eye; Dry Eye Syndrome; DES
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dry Eye Syndromes; thymosin beta(4)
• Other Study ID Numbers: RGN-259/19-110-0002

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