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.

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.

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;