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
Overview
- Phase
- Phase 1
- Intervention
- AVX012 Ophthalmic Solution Low dose
- Conditions
- Dry Eye Syndrome
- Sponsor
- Avizorex Pharma, S.L.
- Enrollment
- 172
- Locations
- 21
- Primary Endpoint
- The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye.
- Last Updated
- 7 years ago
Overview
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):
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).
Investigators
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.
Arms & Interventions
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
Intervention: AVX012 Ophthalmic Solution Low dose
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
Intervention: AVX012 Ophthalmic Solution High dose
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
Intervention: Placebo (vehicle)
Outcomes
Primary Outcomes
The objective of part B is to evaluate the efficacy of AVX-012 ophthalmic solution in treating symptoms of dry eye.
Time Frame: 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).
The objective of part A is to evaluate the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.
Time Frame: 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).
Secondary Outcomes
- Confirm the safety of AVX-012 ophthalmic solution in subjects with dry eye syndrome.(28 days (+7 days))
- Change from baseline in corneal staining 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))
- Change from baseline in Schirmer I test score(28 days (+7 days))