assessing the safety and efficacy of avx-012 in subjects with mild-to-moderate dry eye syndrome

Conditions: Dry Eye Syndrome

Summary: 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).

Eligibility criteria:
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.