The Study Evaluating the Efficacy and Safety of OK-101 in Subjects With Dry Eye Disease

A Phase 2, Multi-center, Randomized, Double-Masked and Placebo-Controlled Study Evaluating the Efficacy and Safety of OK-101 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease

The objective of this study is to compare the safety and efficacy of OK-101 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: Placebo; Drug: OK-101

Detailed Description

Subjects eligible to be randomized will receive either OK-101 or placebo to be administered bilaterally twice daily (BID) for 12 weeks (from Visit 2 to Visit 5). During a 14-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Placebo Ophthalmic Solution (vehicle) bilaterally BID.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Vision Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Butchertown Clinical Trials
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Andover Eye Associates
  • North Carolina
    • Shelby, North Carolina, United States, 28150
      • Core Inc.
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, PA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Be at least 18 years of age;
2. Provide written informed consent;
3. Be willing and able to comply with all study procedures;
4. Have a patient-reported history of dry eye for at least 6 months prior to Visit 1;
5. Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
6. Have a best corrected visual acuity (BCVA) of 0.7 logarithm of the minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1;
7. Report a score of ≥ 2 according to the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire in at least one of the dry eye symptoms at Visits 1 and 2;
8. Have a Schirmer's Test score of ≤ 10 mm and ≥ 1 mm at Visits 1 and 2;
9. Have a corneal fluorescein staining score of ≥ 2 in at least one region according to the Ora Calibra® Corneal and Conjunctival Staining Scale for Grading of Fluorescein Staining in at least one region in one eye at Visits 1 and 2 and a central score ≥ 1 in the same eye;
10. Have a total lissamine green conjunctival score of ≥ 2, based on the sum of the temporal and nasal regions pre-CAE® at Visits 1 and 2;
11. Have a conjunctival redness score ≥ 1 according to the Ora Calibra® Conjunctival Redness for Dry Eye Scale in at least one eye at Visits 1 and 2 pre- CAE;

12. Demonstrate in the same eye(s) a response to the CAE at Visits 1 and 2 as defined by:

    1. Having at least a ≥1 point increase in fluorescein staining in the inferior region in at least one eye following CAE® exposure;
    2. Reporting an Ocular Discomfort score ≥3 at 2 or more consecutive time points in at least one eye during CAE® exposure (if a subject has an Ocular Discomfort rating of 3 at time = 0 for an eye, s/he must report an Ocular Discomfort rating of 4 for two consecutive measurements for that eye). Note: a subject cannot have an Ocular Discomfort score of 4 at time = 0);
13. Have at least one eye, the same eye, satisfy all criteria for 8, 9, 10, 11 and 12 above;
14. A negative urine pregnancy test if female of childbearing potential (those who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or post- menopausal [12 months after last menses]) and must use adequate birth control through the study period. For non-sexually active females, abstinence may be regarded as an adequate method of birth control.

Exclusion Criteria:

1. Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction, ocular rosacea, lid margin inflammation, or active ocular allergies that require therapeutic treatment, or currently using tetracyclines (e.g., doxycycline, minocycline, tetracycline) and/or in the opinion of the investigator may interfere with study parameters;
2. Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
3. Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study;
4. Have previously had laser-assisted in situ keratomileusis (LASIK) surgery, Photorefractive keratectomy (PRK), or small incision lenticule extraction (SMILE) within the last 12 months;
5. Have used Restasis®, Xiidra®, Cequa®, Tyrvaya®, serum tears, generic cyclosporine A, and EYSUVIS® within 30 days of Visit 1;
6. Have had any ocular and/or lid surgeries in the past 6 months or have any planned ocular and/or lid surgeries over the study period;
7. Any use of Lipiflow, thermopulsation, Meibomian gland expression or intense pulsed light treatment within 6 months of visit 1
8. Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1 or have permanent punctal plugs or had surgical punctal occlusion;

9. 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); the respective wash-out periods are required for the following medications:

   1. Antihistamines (including ocular): 72 hours prior to Visit 1
   2. Oral aspirin or aspirin-containing products allowed if dose has been stable over past 30 days prior to Visit 1 and no change in dose is anticipated during the study period
   3. Corticosteroids or mast cell stabilizers (including ocular): 14 days prior to Visit 1
   4. Any medication (oral or topical) known to cause ocular drying that has not been administered as a stable dose for at least 30 days prior to Visit 1 and during the study
   5. Neurostimulators: 30 days prior to Visit 1
   6. Current use or planned use of Prokera® during study conduct or within 30 days prior to Visit 1
   7. All other topical ophthalmic preparations (including artificial tear substitutes) other than the study drops: 72 hours prior to Visit 1
10. Have an uncontrolled systemic disease;
11. Be a woman who is pregnant, nursing, or planning a pregnancy;
12. Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 6 (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 tubal ligation), or is postmenopausal (without menses for 12 consecutive months);
13. 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; 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;
14. Have a known allergy and/or sensitivity to the test article or its components;
15. 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;
16. Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; OK-101 Placebo Ophthalmic Solution (vehicle): 1 drop BID in each eye (N = ~80)	Drug: Placebo; Placebo
Experimental: Low Dose OK-101; 0.05% OK-101 Ophthalmic Solution: 1 drop BID in each eye (N = ~80)	Drug: OK-101; Ophthalmic Solution
Experimental: High-Dose OK-101; 0.1% OK-101 Ophthalmic Solution: 1 drop BID in each eye (N = ~80)	Drug: OK-101; Ophthalmic Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Corneal Fluorescein Staining	Total corneal fluorescein staining score of the study eye using the Ora Calibra® scale, measured by mean change from baseline (Visit 2 pre-CAE®) to Day 85 (Visit 6). Each of the 5 areas will be scored on a scale of 0 to 4 for a total minimum score of 0 to total maximum score of 20, with 0 being best and 20 being worst.	85 days
Ocular Discomfort Score	Ocular discomfort score of both eyes using the Ora Calibra® scale, measured by mean change from baseline (Visit 2 pre-CAE®) to Day 85 (Visit 6). Each eye will be scored separately on a scale from 1 to 4, with 1 being best and 4 being worst.	85 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorescein Staining by Region	Fluorescein staining by region: central, superior, inferior, temporal, nasal, corneal sum, conjunctival sum, and total staining of each eye using the Ora Calibra® scale. Each of the 5 areas will be scored on a scale of 0 to 4 for a total minimum score of 0 to total maximum score of 20, with 0 being best and 20 being worst	85 days
Lissamine Green Staining by Region	Lissamine green staining by region: central, superior, inferior, temporal, nasal, corneal sum, conjunctival sum, and total staining of each eye using the Ora Calibra® scale. Each of the 5 areas will be scored on a scale of 0 to 4 for a total minimum score of 0 to total maximum score of 20, with 0 being best and 20 being worst.	85 days
Conjunctival Redness	Conjunctival redness of each eye using the Ora Calibra® scale. Each eye will be graded on a scale of 0 to 4, with 0 being best and 4 being worst.	85 days
Schirmer's Test	Schirmer's Test of each eye	85 days

Collaborators and Investigators

• Sponsor: Okyo Pharma Ltd
• Collaborators: ORA, Inc.
• Investigators: Study Director: Raj Patil, PhD, Okyo Pharma Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: 22-110-0018

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