Assessing the Safety and Efficacy of AVX-012 in Subjects With Mild-to-moderate Dry Eye Syndrome

Dry Eye Syndrome Clinical Trial

— AVX012CT001  

Official title:

A Phase I/II, Double-blind, Placebo-controlled Study Assessing the Safety and Efficacy of AVX-012 Ophthalmic Solution in Subjects With Mild-to-moderate Dry Eye Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03162094
• Other study ID #: AVX012 CT001
• Secondary ID: 2016-001022-34
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 3, 2017
• Est. completion date: December 2018

Study information

• Verified date: April 2018
• Source: Avizorex Pharma, S.L.
• Contact: Avziorex Pharma, S.L.
• Phone: +34934029026
• Email: patrick.tresserras[@]avxpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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):

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dry Eye Syndrome
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca
• Syndrome

Intervention

Drug:
• AVX012 Ophthalmic Solution Low dose
Ocular topical administration of AVX Ophthalmic Solution Low dose
• AVX012 Ophthalmic Solution High dose
Ocular topical administration of AVX Ophthalmic Solution High dose
• Placebo (vehicle)
Ocular topical administration of placebo (vehicle Ophthalmic Solution)

Locations

Country	Name	City	State
Spain	Clínica Oftalvist Vistahermosa	Alicante
Spain	Centro de Oftalmologia Barraquer	Barcelona
Spain	H Clinic	Barcelona
Spain	H General de Cataluña	Barcelona
Spain	H Germas Trias Pujol	Barcelona
Spain	H Vall de Hebron	Barcelona
Spain	Innova Ocular ICO Barcelona	Barcelona
Spain	clínica Oftalvist Granada	Granada
Spain	Clinica Oftalvist Jerez	Jerez De La Frontera	Cadiz
Spain	Clínica Oftalvist Moncloa	Madrid
Spain	Clínica Universitaria de Navarra_ Madrid	Madrid
Spain	H Clínico San Carlos	Madrid
Spain	H Universitario Ramón y Cajal	Madrid
Spain	Hospital General Universitario Reina Sofía	Murcia
Spain	Instituto Oftalmológico Fernández Vega	Oviedo
Spain	Clínica Universitaria de Navarra	Pamplona	Navarra
Spain	clinica Oftalvist Valencia	Valencia
Spain	Hospital Universitario La Fé	Valencia
Spain	Instituto Universitario de Oftalmobiología Aplicada (IOBA)	Valladolid
Spain	H Miguel Servet	Zaragoza
Spain	H Universitario Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Avizorex Pharma, S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The objective of part A is to evaluate the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.	Evaluation of vital signs (blood pressure and heart rate), laboratory analyses (haematology, biochemistry, and urine pregnancy test), best-corrected visual acuity (ETDRS), corneal anaesthesia (Cochet-Bonnet), intraocular pressure, biomicroscopy/staining (fluorescein), and ophthalmoscopy (dilated).	7 days (+1 day)
Primary	The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye.	Percentage of patients achieving an improvement = 20 points in the Symptom Assessment in Dry Eye (SANDE) questionnaire according to the different dosing frequencies (TID and BID).	28 days (+7 days)
Secondary	Confirm the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.	Percentage of patients with adverse events from baseline (treatment period and post-treatment safety follow-up) according to the different dosing frequencies (TID and BID).	28 days (+7 days)
Secondary	Change from baseline in corneal staining score		28 days (+7 days)
Secondary	Change from baseline in Schirmer I test score		28 days (+7 days)
Secondary	Change from baseline in tear film break up time score		28 days (+7 days)
Secondary	Change from baseline in conjunctival staining score		28 days (+7 days)