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

Sponsor

Avizorex Pharma, S.L. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03162094

Collaborator

(none)

172

Enrollment

Locations

Arms

19.9

Anticipated Duration (Months)

8.2

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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):

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Drug: AVX012 Ophthalmic Solution Low dose Drug: AVX012 Ophthalmic Solution High dose Drug: Placebo (vehicle)	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

172 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase I: patient will be included on 3 arms of treatment ( Placebo, Low dose or High dose AVX-012) TID Phase II: Patient will be included on 4 arms of treatment (Placebo/Dose) BID/TIDPhase I: patient will be included on 3 arms of treatment ( Placebo, Low dose or High dose AVX-012) TID Phase II: Patient will be included on 4 arms of treatment (Placebo/Dose) BID/TID

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

phase I/II, double-blind

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 3, 2017

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

The objective of part A is to evaluate the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome. [7 days (+1 day)]
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).
The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye. [28 days (+7 days)]
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).

Secondary Outcome Measures

Confirm the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome. [28 days (+7 days)]
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).
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinica Oftalvist Jerez	Jerez De La Frontera	Cadiz	Spain	11407
2	Clínica Universitaria de Navarra	Pamplona	Navarra	Spain	31008
3	Clínica Oftalvist Vistahermosa	Alicante		Spain	03015
4	Innova Ocular ICO Barcelona	Barcelona		Spain	08006
5	Centro de Oftalmologia Barraquer	Barcelona		Spain	08021
6	H Vall de Hebron	Barcelona		Spain	08035
7	H Clinic	Barcelona		Spain	08036
8	H General de Cataluña	Barcelona		Spain	08190
9	H Germas Trias Pujol	Barcelona		Spain	08916
10	clínica Oftalvist Granada	Granada		Spain	18004
11	Clínica Universitaria de Navarra_ Madrid	Madrid		Spain	28027
12	Clínica Oftalvist Moncloa	Madrid		Spain	28028
13	H Universitario Ramón y Cajal	Madrid		Spain	28034
14	H Clínico San Carlos	Madrid		Spain	28040
15	Hospital General Universitario Reina Sofía	Murcia		Spain	30003
16	Instituto Oftalmológico Fernández Vega	Oviedo		Spain	33012
17	clinica Oftalvist Valencia	Valencia		Spain	46004
18	Hospital Universitario La Fé	Valencia		Spain	46026
19	Instituto Universitario de Oftalmobiología Aplicada (IOBA)	Valladolid		Spain	47011
20	H Miguel Servet	Zaragoza		Spain	50004
21	H Universitario Lozano Blesa	Zaragoza		Spain	50009

Sponsors and Collaborators

Avizorex Pharma, S.L.

Investigators

Study Director: Patrick Tresserras, Avizorex Pharma, S.L.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Avizorex Pharma, S.L.

ClinicalTrials.gov Identifier:

NCT03162094

Other Study ID Numbers:

AVX012 CT001
2016-001022-34

First Posted:

May 22, 2017

Last Update Posted:

Oct 1, 2018

Last Verified:

Apr 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Dry Eye Syndromes

Keratoconjunctivitis Sicca

Syndrome

Pharmaceutical Solutions

Ophthalmic Solutions

Study Results

No Results Posted as of Oct 1, 2018