Clinical trial: Phase 2/3 Dose-Ranging Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca (NCT02254265)

Eligibility criteria:
Inclusion Criteria:

          1. Subjects age 18 years or older on the date of informed consent.

          2. All subjects must provide signed written consent prior to participation in any
             study-related procedures.

          3. Patient-reported history of KCS for a period of at least 6 months.

          4. Clinical diagnosis of bilateral KCS supported by OTX-101-2014-001 study assessments.

          5. Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible
             score of 12 (scoring excludes superior zones 2 and 4) in the same eye at Screening and
             Baseline.

          6. Global symptom score ≥ 40 at both Screening and Baseline.

          7. Corrected Snellen VA of better than 20/200 in each eye.

          8. Willing to discontinue use of current dry eye therapy (including artificial tears or
             ocular lubricants) during the study as of the run-in period.

          9. Female subjects of childbearing potential must have a negative urine pregnancy test at
             Screening. Women of childbearing potential (ie, women who are not either
             postmenopausal for one year or surgically sterile) must use an acceptable form of
             contraception throughout the study.

        Exclusion Criteria:

          1. Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to
             Screening.

          2. Previous treatment failure (lack of efficacy) on cyclosporine ophthalmic emulsion
             0.05% (Restasis).

          3. Diagnosed with Sjögren's disease ˃5 years prior to Screening.

          4. Clinical diagnosis of seasonal and perennial allergic conjunctivitis.

          5. Use of systemic and topical medications that are known to cause dry eye within 7 days
             prior to Screening and throughout the study period. These include the following
             medications:

               -  Immunomodulators (permitted if dose is stable for 3 months prior to screening and
                  does not change during the study period)

               -  Antihistamines (including over-the counter (OTC))

               -  Cholinergics

               -  Antimuscarinics

               -  Tricyclic antidepressants

               -  Phenothiazines

               -  Retinoids

          6. Oral omega-3 fatty acids (permitted if dose is stable for 3 months prior to Screening
             and does not change during the study period)

          7. Use of any topical ophthalmic medications, prescription (including antiglaucoma
             medications) or OTC (including artificial tears), other than the assigned study
             medication during the study period.

          8. Current active eye disease other than KCS (i.e., any disease for which topical or
             systemic ophthalmic medication is necessary).

          9. History of herpes keratitis.

         10. Unstable macular disease (e.g., age-related macular degeneration, diabetic
             maculopathy). Stable macular disease is defined as no reduction in central VA within 6
             months prior to Screening.

         11. Diagnosis of chronic uveitis.

         12. Corneal transplant (e.g., penetrating keratoplasty, lamellar keratoplasty, Descemet's
             stripping endothelial keratoplasty (DSEK) ).

         13. Corneal refractive surgery (e.g., laser-assisted in situ keratomileusis (LASIK]) photo
             refractive keratectomy (PRK), limbal relaxing incision (LRI) ) within 6 months prior
             to screening or postoperative refractive surgery symptoms of dryness that have not
             resolved.

         14. Cataract surgery within 3 months prior to Screening.

         15. Non-laser glaucoma surgery at any time; glaucoma laser procedures within 3 months
             prior to Screening.

         16. Presence of punctal plugs or past history of permanent punctal occlusion (e.g.,
             cautery).

         17. Lagophthalmos or clinically significant eyelid margin irregularity of the study eye
             whether congenital or acquired.

         18. Presence of conjunctivochalasis (i.e., mechanical blockage of the lower lid punctum by
             redundant conjunctiva).

         19. Presence of pterygium in the study eye.

         20. Unwilling to discontinue use of contact lenses during the duration of the study.

         21. Preplanned elective surgery or hospitalization during the study period.

         22. HIV-positive.

         23. Unable to reliably report symptoms and history.

         24. Has known hypersensitivity or contraindication to the study medication(s) or their
             components.

         25. Has a history or presence of chronic generalized systemic disease that the
             Investigator feels might increase the risk to the subject or confound the result(s) of
             the study.

         26. Has a severe/serious ocular condition, or any other unstable medical condition that,
             in the Investigator's opinion, may preclude study treatment or follow-up.

         27. Women who are pregnant or breastfeeding.

         28. Participation in any drug or device clinical investigation within 30 days prior to
             entry into this study and/or during the period of study participation.

         29. Previous randomization into this study.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 40-year-old woman comes to the clinic complaining of gritty sensation in her eyes. She also has difficulty swallowing dry foods with no pain or heartburn.  The patient is a schoolteacher and must drink water frequently during lectures due to her mouth dryness.  She also reports occasional joint pain.  Medical history is not significant other than the confirmed Sjogren disease with no other rheumatologic disease.  She is sexually active with her husband and has 2 children both delivered by natural vaginal delivery. She has no history of any kind of surgery. Physical examination shows conjunctival erythema and cracking of the lips. The remainder of the examination and history is normal. Her lab result shows elevated ESR (50 mm/h)

Patient description (patient's own words): I went to the clinic because I had a terrible gritty sensation in my eyes. It was also hard to swallow dry food, but it didn't burn, and there was no pain. I'm a 40-year-old female school teacher and I should drink water for the lectures because otherwise, my mouth gets really dry. I also have joint pain from time to time. I have been diagnosed with Sjogren disease but no other rheumatologic disease. I have a husband, we're sexually active, and I also have two lovely children that I delivered both naturally. I never undergone any surgery. Physical examination when I came to the clinic, and it showed cracking on my lips and a pink eye. The rest was fine. I also did some lab tests, and they came back with high ESR.

Does the patient match the trial criteria? Contradiction