Lacripep™ in Subjects With Dry Eye Associated With Primary Sjögren's Syndrome

A Double-Masked, Randomized, Multi-Center Phase 2 Study to Evaluate the Efficacy and Safety of Lacripep™ in Subjects With Dry Eye Associated With Primary Sjögren's Syndrome

The objective of this study is to evaluate the efficacy and safety of two strengths of Lacripep™ ophthalmic solution versus placebo administered three times daily for four weeks in subjects with a diagnosis of Dry Eye associated with documented Primary Sjögren's Syndrome

This is a multi-center, randomized, placebo-controlled, double-masked, parallel-group study. Subjects will be randomized into three treatment groups: 0.005%, or 0.01% Lacripep™, or placebo in a 1:1:1 ratio.

Inclusion Criteria:

Subjects who meet the following criteria will be selected:

1. Subjects who are age 18 years of age or older at the time of obtaining informed consent.

2. Subjects with a documented prior history or current diagnosis of Primary Sjögren's Syndrome according the American-European Consensus Group Sjögren's Syndrome Criteria (Appendix 4; must meet either 4 out of 6 total criteria OR 3 out of 4 signs). Note: Subjects who are on systemic (oral) therapy for the treatment of Sjögren's Syndrome must be on stable systemic treatment defined as the same treatment for the immediately prior 90 days.

3. Subjects with a history of dry eye-related ocular symptoms, and who have self-reported use of over the counter ocular wetting agents within the last 120 days.

4. Subjects who meet the following criteria at both screening and Visit 2 (Randomization/Baseline) examinations:

   1. FCS total score ≥ 4 and < 15 in the NEI/Industry Workshop scale, (Appendix 6)
   2. Symptom Severity score of ≥ 40 using the SANDE questionnaire (Appendix 3)
   3. Anesthetized Schirmer test score ≤ 5 mm wetting/5 min
   4. LGCS total score ≥ 5 using the NEI/Industry Workshop scale (where 0=no staining) Note: Subjects must meet all 4 criteria and eligible scores for FCS, Anesthetized Schirmer and LGCS must be in at least one eye and it must be in the same eye at the time of the visit.

Exclusion Criteria:

Subjects meeting any of the following criteria at the Visit 1 (Screening) or Visit 2 (Randomization/Baseline) visits will be excluded:

1. Subjects with any active infectious ocular condition.
2. Subjects who are monocular or have a BCVA, using corrective lenses if necessary, of +1.0 logMAR or worse as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS).
3. Subjects with ocular inflammatory conditions (e.g., conjunctivitis, keratitis, anterior blepharitis, etc.) not related to dry eye syndrome.
4. Subjects with clinical evidence of cicatricial ocular surface disease, such as cicatricial ocular pemphigoid or Stevens Johnson syndrome.
5. Subjects who cannot suspend the use of any topical eye medications (including topical cyclosporine) other than the investigational product during the run-in and the study treatment phase.
6. Subjects who have used Restasis® (topical ophthalmic cyclosporine) or Xiidra® (topical ophthalmic lifitegrast) within 14 days prior to Visit 1.
7. Subjects who in the study eye have fluorescein corneal staining (FCS) Total Score = 15 or a Score = 3 in the superior region per the NEI/Industry Workshop scale or subjects who have FCS with diffuse confluent staining, filaments or frank epithelial defects.
8. Subjects who have active or have had an outbreak of herpetic keratitis within 365 days of Visit 1 or subjects who are on chronic oral antivirals for ocular herpetic disease.
9. Subjects who cannot suspend the use of and abstain from contact lens use from the Screening Visit (Visit 1) to the end of the study (Visit 5).
10. Subjects who have a history of collagen vascular disease, auto immune disease or rheumatic disease other than Primary Sjögren's Syndrome (e.g., Lupus, Rheumatoid Arthritis, etc.).
11. Subjects who have a history of or current Anterior Membrane Dystrophy.
12. Subjects who have had a corneal transplant or similar corneal surgery (DALK, DSEK, DMEK, etc.).
13. Subjects who have used or anticipate use of amiodarone.
14. Subjects who within 30 days prior to Visit 1 alter the dose or anticipate alterations to the dose of the following: tetracyclines, Omega 3's or 6's.
15. Subjects who within 60 days prior to Visit 1 and for the duration of the study alter the dose or anticipate alterations to the dose of the following: anticholinergics, antidepressants, oral contraceptives, isotretinoin, oral systemic corticosteroids, oral systemic immunosuppressive agents.
16. Subjects who within 30 days prior to Visit 1 and for the duration of the study use topical ocular antihistamines, ocular, inhaled or intranasal corticosteroids, topical or oral mast cell stabilizers, oral antihistamines, topical or nasal vasoconstrictors, topical ocular NSAIDs, topical ocular antibiotics or serum tears.
17. Subjects who in the study eye have had cauterization of the punctum or alterations to (insertion or removal) punctal plug(s) within the past 14 days prior to Visit 1. Note: If a punctal plug in place at Visit 2 (Randomization/Baseline) and it is dislodged, the plug should be replaced as soon as possible.
18. Subjects who, in the study eye, have had corneal refractive surgery (LASIK, PRK, RK).
19. Subjects who in the study eye, have a history of any operative procedure on the ocular surface or eyelids within 365 days prior to Visit 1 or with a history of intraocular surgery within 90 days prior to Visit 1.
20. Subjects who are pregnant or suspected to be pregnant and subjects who are breastfeeding or intend to breastfeed. Female subjects of childbearing potential are required to have a negative urine pregnancy test at screening, and must agree to use an acceptable method of contraception from the time of signing informed consent until the end of study visit. Medically acceptable contraception methods include intrauterine device; barrier methods such as diaphragm, condom, cap or sponge, used with a spermicide; or hormonal contraception.
21. Subjects with any physical or mental impairment that would preclude participation and the ability to give informed consent.
22. Subjects who have participated in a device or Investigational drug study or clinical trial within 30 days of Visit 1. Participation in another during this study is excluded for the duration of this study.