A Study Evaluating the Efficacy and Safety of RCI001 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye

Inclusion criteria

• 1. Be at least 18 years of age at the Screening Visit (Visit 1), of either gender and any race; 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 l; 5. Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit l; 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 l; 7. Report a score of ≥ 3 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 total corneal fluorescein staining score of ≥ 6 and an inferior region score of ≥ 2 (in the same eye) according to the Ora Calibra® Corneal and Conjunctival Staining Scale in at least in at least one eye at Visits 1 and 2 pre-CAE®; 10. Have a total conjunctival lissamine green staining score of ≥ 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:

• Having at least a ≥ 1 point increase in fluorescein staining in the inferior region in at least one eye following CAE® exposure;
• 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 l that may include active blepharitis, meibomian gland dysfunction, severe lid margin inflammation, or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters; Note: Patients with moderate to severe meibomian gland dysfunction, in the opinion of the investigator, will not be eligible to participate in the study.

• Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit l; 3. Have worn contact lenses within 7 days of Visit l or anticipate using contact lenses during the study; 4. Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last l2 months; 5. Have used Restasis®, Xiidra®, Cequa®, Eysuvis®, or Tyrvaya®, Vevye® within 45 days of Visit l; 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. Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit l; 8. 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: Confidential 6
• Antihistamines (including ocular): 72 hours prior to Visit 1
• 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
• Corticosteroids or mast cell stabilizers (including ocular): l4 days prior to Visit 1
• 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
• All other topical ophthalmic preparations (including artificial tear substitutes) other than the study drops: 72 hours prior to Visit 1 9. Have an uncontrolled systemic disease 10. Be a woman who is pregnant, nursing, or planning a pregnancy; 11. Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 4 (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 post- menopausal (without menses for l2 consecutive months); 12. 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; 13. Have a known allergy and/or sensitivity to the test article or its components; 14. 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; 15. Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1; 16. Be unable or unwilling to follow instructions, including participation in all study assessments and visits.