A Phase 3, Multi-Center Study Evaluating PL9643 in Patients with Dry Eye

A Phase 3, Multi-center, Randomized, Double-Masked and Vehicle-Controlled Study Evaluating the Efficacy and Safety of the Melanocortin, PL9643 Ophthalmic Solution, Compared to Vehicle in Subjects with Dry Eye

This is a multi-center, double-masked, randomized, vehicle-controlled study testing PL9643, an ophthalmic solution to determine if safe and efficacious for dry eye patients.

After a 2-week run-in period, patients will be randomized equally to the PL9643 ophthalmic solution or vehicle ophthalmic solution administered bilaterally three times a day for 12 weeks.

A Data Monitoring Committee was engaged to review interim data.

This is a multi-center, double-masked, randomized, vehicle-controlled study testing PL9643, an ophthalmic solution, to determine the safety and efficacy against a vehicle in dry eye patients.

During a 2-week/14-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Vehicle Ophthalmic Solution (vehicle) bilaterally three times a day. Randomization will then occur in a 1:1 ratio where patients will be assigned to receive PL9643 ophthalmic solution given bilaterally three times a day or vehicle ophthalmic solution administered bilaterally three times a day. The treatment period is 12 weeks.

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 5 years 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. Have an inferior fluorescein corneal staining score > 1 at both Visits 1 and 2 Pre-CAE®;

8. Have an Eye Discomfort from the Visual Analog Scale (VAS) ≥25 at both Visits 1 and 2 Pre-CAE®;

9. 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 Pre-CAE®;

10. Have a Schirmer's Test score of ≤ 10 mm and ≥ 1 mm at Visits 1 and 2;

11. Have a corneal fluorescein staining score of ≥ 2 in any corneal region (inferior, central or superior) according to the Ora Calibra® Corneal and Conjunctival Staining Scale for Grading of Fluorescein Staining in at least one eye at Visits 1 and 2 Pre-CAE®;

12. 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®;

13. 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);

14. Have at least one eye, the same eye, satisfy all criteria for 7, 8, 9, 10, 11, 12 and 13 above;

15. 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, lid margin inflammation, or active ocular allergies that require therapeutic treatment, 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 or Visit 2;

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 within the last 12 months;

5. Have used Restasis®, Xiidra®, Cequa®, or Eysuvis® within 60 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. Have had any laser procedures (e.g. YAG capsulotomy) in the past 3 months;

8. Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;

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 thefollowing medications:

   1. Ocular, oral or nasal antihistamines: 72 hours prior to Visit 1 and during the study.
   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. 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., bilateral tubal ligation, hysterectomy or bilateral oophorectomy), or is post-menopausal (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. Have used an investigational drug or device within 30 days of Visit 1 unless the Investigator or Sponsor deems a washout period of up to 60 days is required;

17. Participated in a previous clinical study involving PL9643;

18. Be unable or unwilling to follow instructions, including participation in all study assessments and visits.