Treatment of Dry Eye Disease Using Pro-ocular™ - A Proof of Concept, Safety, and Efficacy Study

To evaluate the safety and efficacy of 1% Pro-ocular topical gel administered twice daily for 12 weeks in treatment of Dry Eye Disease

Study Overview

• Status: Enrolling by invitation
• Conditions: Keratoconjunctivitis Sicca; Dry Eye Syndrome
• Intervention / Treatment: Drug: Pro-ocular™ Topical Gel; Drug: Placebo Topical Gel

Detailed Description

Pro-ocular™ 1% topical gel his demonstrated efficacy in rapidly reducing or eliminating dry eye symptoms, and after multiple doses, the signs and symptoms of ocular surface disease including dry eye disease.

Study DE-2 is single center, randomized, double-masked, placebo-controlled, parallel-group study designed to evaluate the safety and efficacy of 1% Pro-ocular topical gel administered twice daily for 12 weeks for treatment of Dry Eye Disease. The approximately 80 subjects will be randomized 1:1, active drug:placebo.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei City, Taiwan, 11490
    • Tri-Service General Hospital, National Defense Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female of any race, at least 20 years of age at Visit 1 Screening.
2. Has a subject reported history (including physician diagnosis) of dry eye disease in both eyes for at least 3 months prior to Visit 1.
3. Has SANDE score ≥50 in either frequency or severity of symptoms of dryness and/or irritation at Visit 1.

4. Have all of the following in the same eye at Visit 1:

   1. Fluorescein Tear Break-Up Time of ≤5 seconds.
   2. Corneal fluorescein staining score of moderate or more in any field (inferior, superior or central).
   3. Report a severity score of moderate or more on ocular dryness and at least one of the other symptoms on the GLIA Ocular Surface Disease Symptoms Questionnaire.
5. Has provided written informed consent.
6. Be able and willing to follow oral and written instructions, including participation in all study assessments and visits.

Exclusion Criteria:

1. Comorbidity with other severe or chronic eye conditions that in the judgment of the investigator will interfere with study assessments, such as but not limited to corneal opacities and scars, dystrophies, epithelial scarring, infections, history of blood clots, etc.
2. Has infections, or inflammatory skin lesion in or around the dosing area.
3. Best corrected visual acuity baseline <20/200.
4. Has a condition or history that, in the opinion of the investigator, may interfere significantly with the subject's participation in the study.
5. Wear contact lens within 7 days prior to Visit 1.
6. Anticipate change of vision correction or anticipate any ocular procedures during study period.
7. A woman who is pregnant or testing positive in the blood pregnancy test at screening, nursing an infant, or planning a pregnancy.
8. Has a known adverse reaction and/or sensitivity to the study drug or its components.
9. Use of topical ocular cyclosporine (e.g. Restasis®), lifitegrast (Xiidra®), diquafosol (Diquas®), eye gels, eye ointments, any administration route of steroids, anti-histamines, antipsychotics, antidepressants and NSAIDs within 30 days prior to Visit 1.
10. Routine use (more than once a week) of a chlorinated swimming pool during study period.
11. Unwilling or unable to cease using the following medications during the study period (from Visit 1 to Visit 6): Topical ocular cyclosporine (e.g. Restasis®), lifitegrast (Xiidra®), diquafosol (Diquas®), eye gels, eye ointments, any administration route of steroids, anti-histamines, antipsychotics, antidepressants and NSAIDs..
12. Unwilling to cease the use of sunscreen and face scrubs on the forehead or eye area during study period.
13. Smoke within 3 months prior to Visit 1.
14. Ongoing glaucoma treatment within 30 days prior to Visit 1 and during study period.
15. Currently enrolled in an investigational drug or device study within 30 days prior to Visit 1 and during study period.

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
Active Comparator: Pro-ocular™; Pro-ocular™ Topical Gel	Drug: Pro-ocular™ Topical Gel; Pro-ocular™ Topical Gel 1% is applied dermally to the forehead twice-daily; Other Names: PG101
Placebo Comparator: Placebo; Placebo Topical Gel	Drug: Placebo Topical Gel; Placebo is a toopical gel without active ingredient applied dermally to the forehead twice-daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Frequency score	Change from baseline in SANDE symptoms frequency score (0-100 worst)	2 weeks
Change in corneal (central) fluorescein staining score	Change from baseline in score on a visual analog scale (0-10 worst)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Global score	Change from baseline in SANDE symptoms global score (0-100 worst)	2 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Global score	Change from baseline in SANDE symptoms global score (0-100 worst)	4 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Global score	Change from baseline in SANDE symptoms global score (0-100 worst)	8 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Global score	Change from baseline in SANDE symptoms global score (0-100 worst)	12 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Frequency score	Change from baseline in SANDE symptoms frequency score (0-100 worst)	4 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Frequency score	Change from baseline in SANDE symptoms frequency score (0-100 worst)	8 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Frequency score	Change from baseline in SANDE symptoms frequency score (0-100 worst)	12 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Severity score	Change from baseline in SANDE symptoms severity score (0-100 worst)	2 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Severity score	Change from baseline in SANDE symptoms severity score (0-100 worst)	4 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Severity score	Change from baseline in SANDE symptoms severity score (0-100 worst)	8 weeks
Change in SANDE (Symptom Assessment iN Dry Eye) Questionnaire Severity score	Change from baseline in SANDE symptoms severity score (0-100 worst)	12 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) ocular discomfort score	Change from baseline in GLIA OSDSQ ocular discomfort score (0-10 worst)	1 hour
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) ocular discomfort score	Change from baseline in GLIA OSDSQ ocular discomfort score (0-10 worst)	2 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) ocular discomfort score	Change from baseline in GLIA OSDSQ ocular discomfort score (0-10 worst)	4 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) ocular discomfort score	Change from baseline in GLIA OSDSQ ocular discomfort score (0-10 worst)	8 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) ocular discomfort score	Change from baseline in GLIA OSDSQ ocular discomfort score (0-10 worst)	12 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) sum of scores	Change from baseline in GLIA OSDSQ sum of scores (highest worst)	1 hour
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) sum of scores	Change from baseline in GLIA OSDSQ sum of scores (highest worst)	2 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) sum of scores	Change from baseline in GLIA OSDSQ sum of scores (highest worst)	4 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) sum of scores	Change from baseline in GLIA OSDSQ sum of scores (highest worst)	8 weeks
Change in GLIA (Ocular Surface Disease Symptoms Questionnaire) sum of scores	Change from baseline in GLIA OSDSQ sum of scores (highest worst)	12 weeks
Change in Tear Film Grading by TearScan examination	Change from baseline in tear film grade (0-3 best)	1 hour
Change in Tear Film Grading by TearScan examination	Change from baseline in tear film grade (0-3 best)	2 weeks
Change in Tear Film Grading by TearScan examination	Change from baseline in tear film grade (0-3 best)	4 weeks
Change in Tear Film Grading by TearScan examination	Change from baseline in tear film grade (0-3 best)	8 weeks
Change in Tear Film Grading by TearScan examination	Change from baseline in tear film grade (0-3 best)	12 weeks
Change in Meibography score by Keratograph®	Change from baseline using Grades 0 to 3 (0 no loss to 3 >2/3 loss)	12 weeks
Change in Tear Meniscus Height (TMH) by Keratograph®	Change from baseline in mm TMH (higher is better)	1 hour
Change in Tear Meniscus Height (TMH) by Keratograph®	Change from baseline in mm TMH (higher is better)	4 weeks
Change in Tear Meniscus Height (TMH) by Keratograph®	Change from baseline in mm TMH (higher is better)	8 weeks
Change in Tear Meniscus Height (TMH) by Keratograph®	Change from baseline in mm TMH (higher is better)	12 weeks
Change in Non-Invasive Keratograph® Tear Break-Up Time (NIKBUT)	Change from baseline in NIKBUT in seconds (longer is better)	1 hour
Change in Non-Invasive Keratograph® Tear Break-Up Time (NIKBUT)	Change from baseline in NIKBUT in seconds (longer is better)	4 weeks
Change in Non-Invasive Keratograph® Tear Break-Up Time (NIKBUT)	Change from baseline in NIKBUT in seconds (longer is better)	8 weeks
Change in Non-Invasive Keratograph® Tear Break-Up Time (NIKBUT)	Change from baseline in NIKBUT in seconds (longer is better)	12 weeks
Change in Bulbar redness score by Keratograph®	Change from baseline in Bulbar redness score (highest is worst)	1 hour
Change in Bulbar redness score by Keratograph®	Change from baseline in Bulbar redness score (highest is worst)	4 weeks
Change in Bulbar redness score by Keratograph®	Change from baseline in Bulbar redness score (highest is worst)	8 weeks
Change in Bulbar redness score by Keratograph®	Change from baseline in Bulbar redness score (highest is worst)	12 weeks
Change in tear film osmolarity by TearLab™ osmolarity system	Change from baseline in mOsms/L (higher value is worse)	1 hour
Change in tear film osmolarity by TearLab™ osmolarity system	Change from baseline in mOsms/L (higher value is less sensitive)	2 weeks
Change in corneal sensitivity using Cochet-Bonnet esthesiometer	Change from baseline in mm Hg (higher is less sensitive)	1 hour
Change in corneal sensitivity using Cochet-Bonnet esthesiometer	Change from baseline in mm Hg (higher is less sensitive)	2 weeks
Change in corneal sensitivity using Cochet-Bonnet esthesiometer	Change from baseline in mm Hg (higher is less sensitive)	4 weeks
Change in corneal sensitivity using Cochet-Bonnet esthesiometer	Change from baseline in mm Hg (higher is less sensitive)	8 weeks
Change in corneal sensitivity using Cochet-Bonnet esthesiometer	Change from baseline in mm Hg (higher is less sensitive)	12 weeks
Change in Fluorescein Tear Break-Up Time (FBUT)	Change from baseline in FBUT in seconds (longer is better)	1 hour
Change in Fluorescein Tear Break-Up Time (FBUT)	Change from baseline in FBUT in seconds (longer is better)	4 weeks
Change in Fluorescein Tear Break-Up Time (FBUT)	Change from baseline in FBUT in seconds (longer is better)	8 weeks
Change in Fluorescein Tear Break-Up Time (FBUT)	Change from baseline in FBUT in seconds (longer is better)	12 weeks
Change in corneal (central) fluorescein staining score	Change from baseline in central corneal fluorescein staining score (0-10 worst)	2 weeks
Change in corneal (central) fluorescein staining score	Change from baseline in central corneal fluorescein staining score (0-10 worst)	8 weeks
Change in corneal (central) fluorescein staining score	Change from baseline in central corneal fluorescein staining score (0-10 worst)	12 weeks
Change in corneal (inferior) fluorescein staining score	Change from baseline in inferior corneal fluorescein staining score (0-10 worst)	2 weeks
Change in corneal (inferior) fluorescein staining score	Change from baseline in inferior corneal fluorescein staining score (0-10 worst)	4 weeks
Change in corneal (inferior) fluorescein staining score	Change from baseline in inferior corneal fluorescein staining score (0-10 worst)	8 weeks
Change in corneal (inferior) fluorescein staining score	Change from baseline in inferior corneal fluorescein staining score (0-10 worst)	12 weeks
Change in corneal (superior) fluorescein staining score	Change from baseline in superior corneal fluorescein staining score (0-10 worst)	2 weeks
Change in corneal (superior) fluorescein staining score	Change from baseline in superior corneal fluorescein staining score (0-10 worst)	4 weeks
Change in corneal (superior) fluorescein staining score	Change from baseline in superior corneal fluorescein staining score (0-10 worst)	8 weeks
Change in corneal (superior) fluorescein staining score	Change from baseline in superior corneal fluorescein staining score (0-10 worst)	12 weeks
Change in corneal fluorescein staining sum of scores	Change from baseline in corneal fluorescein staining sum of scores (0-30 worst)	2 weeks
Change in corneal fluorescein staining sum of scores	Change from baseline in corneal fluorescein staining sum of scores (0-30 worst)	4 weeks
Change in corneal fluorescein staining sum of scores	Change from baseline in corneal fluorescein staining sum of scores (0-30 worst)	8 weeks
Change in corneal fluorescein staining sum of scores	Change from baseline in corneal fluorescein staining sum of scores (0-30 worst)	12 weeks
Change in conjunctival fluorescein staining sum of scores	Change from baseline in conjunctival fluorescein staining sum of scores (0-30 worst)	2 weeks
Change in conjunctival fluorescein staining sum of scores	Change from baseline in conjunctival fluorescein staining sum of scores (0-30 worst)	4 weeks
Change in conjunctival fluorescein staining sum of scores	Change from baseline in conjunctival fluorescein staining sum of scores (0-30 worst)	8 weeks
Change in conjunctival fluorescein staining sum of scores	Change from baseline in conjunctival fluorescein staining sum of scores (0-30 worst)	12 weeks
Change in lissamine green staining (corneal and conjunctival) sum of scores	Change from baseline in lissamine green staining (corneal and conjunctival) sum of scores	2 weeks
Change in lissamine green staining (corneal and conjunctival) sum of scores	Change from baseline in lissamine green staining (corneal and conjunctival) sum of scores (higher is worse)	4 weeks
Change in lissamine green staining (corneal and conjunctival) sum of scores	Change from baseline in lissamine green staining (corneal and conjunctival) sum of scores (higher is worse)	8 weeks
Change in lissamine green staining (corneal and conjunctival) sum of scores	Change from baseline in lissamine green staining (corneal and conjunctival) sum of scores (higher is worse)	12 weeks
Change in conjunctival hyperemia (by slit lamp biomicroscopy)	Change from baseline in conjunctival hyperemia score (0-10 worst)	2 weeks
Change in conjunctival hyperemia (by slit lamp biomicroscopy)	Change from baseline in conjunctival hyperemia score (0-10 worst)	4 weeks
Change in conjunctival hyperemia (by slit lamp biomicroscopy)	Change from baseline in conjunctival hyperemia score (0-10 worst)	8 weeks
Change in conjunctival hyperemia (by slit lamp biomicroscopy)	Change from baseline in conjunctival hyperemia score (0-10 worst)	12 weeks

Collaborators and Investigators

• Sponsor: PharmaDax Inc.
• Collaborators: Glia, LLC
• Investigators: Study Director: Peichun Kuo, PharmaDax Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 20, 2021
• Primary Completion (Anticipated): October 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Dry Eye; Dry Eye Disease; Evaporative Dry Eye; Evaporative Dry Eye Disease; Keratoconjuncitivitis Sicca; Sjogren's Sydrome
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis
• Other Study ID Numbers: DE-2

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