Assessing the Safety and Efficacy of AVX-012 in Subjects With Mild-to-moderate Dry Eye Syndrome (AVX012CT001)

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

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):

Study Overview

• Status: Unknown
• Conditions: Dry Eye Syndrome
• Intervention / Treatment: Drug: AVX012 Ophthalmic Solution Low dose; Drug: AVX012 Ophthalmic Solution High dose; Drug: Placebo (vehicle)

Detailed 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).

• Study Type: Interventional
• Enrollment (Anticipated): 172
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Avziorex Pharma, S.L.; Phone Number: +34934029026; Email: patrick.tresserras@avxpharma.com

Study Locations

• Spain
  • Alicante, Spain, 03015
    • Not yet recruiting
    • Clínica Oftalvist Vistahermosa
    • Contact: Enrique Artiaga Elordi, Dr
  • Barcelona, Spain, 08006
    • Recruiting
    • Innova Ocular ICO Barcelona
  • Barcelona, Spain, 08021
    • Not yet recruiting
    • Centro de Oftalmologia Barraquer
    • Contact: Jose Lamarca Mateu, Dr.
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • H Vall de Hebron
    • Contact: Sara Martin Naldas, Dra.
  • Barcelona, Spain, 08036
    • Recruiting
    • H Clinic
  • Barcelona, Spain, 08190
    • Recruiting
    • H General de Cataluña
  • Barcelona, Spain, 08916
    • Not yet recruiting
    • H Germas Trias Pujol
    • Contact: Antoni Sabala Llopart, Dr
  • Granada, Spain, 18004
    • Not yet recruiting
    • clínica Oftalvist Granada
    • Contact: Eva Delgado Alonso, Dr.
  • Madrid, Spain, 28027
    • Not yet recruiting
    • Clínica Universitaria de Navarra_ Madrid
    • Contact: Javier Moreno Montañes, Dr
  • Madrid, Spain, 28028
    • Not yet recruiting
    • Clínica Oftalvist Moncloa
    • Contact: Enrique Artega Elordi, Dr
  • Madrid, Spain, 28034
    • Recruiting
    • H Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Recruiting
    • H Clinico San Carlos
  • Murcia, Spain, 30003
    • Recruiting
    • Hospital General Universitario Reina Sofía
  • Oviedo, Spain, 33012
    • Recruiting
    • Instituto Oftalmologico Fernandez Vega
  • Valencia, Spain, 46026
    • Not yet recruiting
    • Hospital Universitario La Fe
    • Contact: Salvador García Delpech, Dr
  • Valencia, Spain, 46004
    • Not yet recruiting
    • Clinica Oftalvist Valencia
    • Contact: Francisco Pastor Pascual, Dr
  • Valladolid, Spain, 47011
    • Recruiting
    • Instituto Universitario de Oftalmobiología Aplicada (IOBA)
  • Zaragoza, Spain, 50004
    • Recruiting
    • H Miguel Servet
  • Zaragoza, Spain, 50009
    • Recruiting
    • H Universitario Lozano Blesa
  • Cadiz
    • Jerez De La Frontera, Cadiz, Spain, 11407
      • Not yet recruiting
      • Clinica Oftalvist Jerez
      • Contact: Ramón Ruiz Mesa, Dr
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universitaria de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVX-012 Opthalmic Solution Low dose; Phase I: AVX-012 ophthalmic solution Low dose administration three times per day (TID) for 7 days Phase II: If the low dose of AVX012 is selected on phase I, AVX-012 ophthalmic solution Low dose administration three times per day (TID) and two times per day (BID) for 28 days	Drug: AVX012 Ophthalmic Solution Low dose; Ocular topical administration of AVX Ophthalmic Solution Low dose
Experimental: AVX-012 Opthalmic Solution High dose; Phase I: AVX-012 ophthalmic solution High dose administration three times per day (TID) for 7 days Phase II: If the high dose of AVX012 is selected on phase I, AVX-012 ophthalmic solution High dose administration three times per day (TID) and two times per day (BID) for 28 days	Drug: AVX012 Ophthalmic Solution High dose; Ocular topical administration of AVX Ophthalmic Solution High dose
Placebo Comparator: Placebo (Vehicle) Opthalmic Solution; Phase I: Placebo ophthalmic solution administration three times per day (TID) for 7 days Phase II: Placebo ophthalmic solution administration three times per day (TID) and two times per day (BID) for 28 days	Drug: Placebo (vehicle); Ocular topical administration of placebo (vehicle Ophthalmic Solution)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Change from baseline in corneal staining score		28 days (+7 days)
Change from baseline in Schirmer I test score		28 days (+7 days)
Change from baseline in tear film break up time score		28 days (+7 days)
Change from baseline in conjunctival staining score		28 days (+7 days)

Collaborators and Investigators

• Sponsor: Avizorex Pharma, S.L.
• Investigators: Study Director: Patrick Tresserras, Avizorex Pharma, S.L.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: April 5, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 1, 2018
• Last Update Submitted That Met QC Criteria: September 28, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Disease; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Syndrome; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: AVX012 CT001; 2016-001022-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No