This is a first-in-human phase I/II randomized, double-blind, placebo (vehicle)-controlled, multicenter study to assess the Safety and Efficacy of AVX-012 Ophthalmic Solution in subjects with Mild-to-Moderate Dry Eye Syndrome.

The study consists of two parts (part A and part B):

The study part A will be an early safety assessment of AVX-012 ophthalmic solution (Low dose and High dose AVX-012) administered three times per day (TID) when compared with the vehicle (placebo). Approximately 24 patients will be randomized 1:1:1 to study groups (Low dose AVX-012, High dose AVX-012, or placebo [vehicle]).

An independent safety committee will be in charge of assessing the safety of study treatments to proceed to part B.

The study part B will be an efficacy and safety assessment of the dose of AVX-012 ophthalmic solution selected in the study part A (Low dose or High dose AVX-012) administered three times a day (TID) and twice a day (BID) when compared with the vehicle (placebo). Approximately 148 patients will be randomized 1:1:1:1 to study groups (Low dose or High dose AVX-012 and placebo [vehicle], TID and BID).

Inclusion Criteria:

• Male or female subjects of at least 18 years of age.
• Diagnosis of dry eye (by a health care professional) for at least 3 months prior to screening visit.
• Normal lid anatomy.
• Intraocular pressure less than 22 mmHg (inclusive) in each eye.
• Best-corrected visual acuity measured by ETDRS in each eye of 20/200 (logMAR 1.0) or better.
• Schirmer I test score of ≥ 3 mm to ≤ 9 mm/ 5 min (with anesthesia).
• SANDE symptom score of 50 or more.
• Total ocular staining of minimum 1 in Oxford scale with fluorescein and/or green lissamine.
• Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements.

Exclusion Criteria:

• History of other than dry eye, ocular surface of moderate to severe Meibomian gland disease (grades +++ to ++++ [moderately to severely altered expressibility and secretion quality]: moderate symptoms with mild to moderate corneal staining, mainly peripheral; or marked symptoms with marked corneal staining, central in addition), chronic, or acute ophthalmic disease in either eye, including glaucoma, macular degeneration, clinically significant cataract (primary or secondary).
• Best-corrected visual acuity score of 55 letters read or lower in each eye as measured by ETDRS (letters read method).
• Previous history of drug or any ingredient hypersensitivity.
• Intraocular or strabismus surgery or glaucoma laser surgery within the previous 6 months.
• History of refractive surgery in either eye (e.g., radial keratotomy, PRK, LASIK, etc.).
• Ocular trauma within the past 6 months.
• Relevant ocular pathology judged by the investigator such as; eyelid anomalies, corneal disorders, metaplasia of the ocular surface, current filamentous keratitis, or corneal neovascularization.
• Any history of herpes simplex or herpes zoster keratitis.
• Ocular infection (bacterial, viral, or fungal)
• Ocular medication of any kind, with the exception of artificial tears/gels/lubricants within the past 2 weeks of screening.
• Cyclosporine treatment during the 6 months prior to enrolment.
• Use of systemic medication that might cause dryness in the eye as a secondary effect (such as antihistaminics, hormone replacing therapies, etc.).
• Use of contact lens
• Use of additional artificial tears (other than study treatments) throughout the study, starting at screening visit.
• Participation in an investigational drug or device trial within the 30 days previous to screening visit.
• Any abnormality preventing reliable applanation tonometry of either eye.
• Central corneal thickness greater than 600 μm by conventional pachymetry.
• Signs of severe ocular surface diseases including corneal or conjunctival staining judged as severe by the investigator.
• Clinically significant systemic disease including uncontrolled diabetes, myasthenia gravis, hepatic, renal, cardiovascular, endocrine disorders, previous cerebrovascular accident with a significant residual motor or sensory defect, progressive neurologic disorders (Parkinsonism, dementias, multiple sclerosis, unstable acquired seizure disorders) which might interfere with the study as judged by the investigator.
• Any systemic disease or medication that might course with known dryness in the eye.
• Changes of systemic medication that could have a substantial effect on intraocular pressure within 30 days prior to screening or anticipated during the study.
• Any medical condition (systemic or ophthalmic) that may, in the opinion of the investigator, preclude the safe administration of the investigational product or safe participation in this study.
• Pregnant or breastfeeding females or those with a positive pregnancy test.
• All females of childbearing potential must have a negative urine pregnancy test result at screening, and also agree to abstain from sexual intercourse with a male partner or agree to use a medically acceptable method of birth control (such as condom, diaphragm or cervical/vault cap with spermicide) until 28 days post-treatment. Males should also agree to abstain from sexual intercourse with a female partner or agree to use a condom with spermicide until 28 days post-treatment.

phase I/II, double-blind