3 Month Study of Alocross Versus Vismed in Adults With Dry Eye Disease Related to Keratitis or Keratoconjunctivitis

Study Overview
=================
Brief Summary
-----------------
This study is a prospective, multicentre, parallel-group, active-controlled, non-inferiority study conducted in adult patients with moderate-to-severe dry eye disease (DED) related to keratitis or keratoconjunctivitis. This study is conducted at a national level, in France. The patients will be randomised to receive ALOCROSS® or the reference treatment, VISMED® (ratio 1:1) in an investigator-masked fashion

Detailed Description
-----------------
Primary: • To compare the ocular efficacy of ALOCROSS® with that of VISMED® in patients with moderate to severe DED related to keratitis or keratoconjunctivitis after a 4-week treatment period (Day 28). Secondary: To compare the ocular efficacy of ALOCROSS® with that of VISMED® in patients with moderate to severe DED related to keratitis or keratoconjunctivitis over a 12-week treatment period To evaluate the ocular tolerability and safety of ALOCROSS® versus VISMED® in patients with moderate to severe DED related to keratitis or keratoconjunctivitis throughout the duration of treatment

Official Title
-----------------
A 3-month, Prospective, Multicentre, Investigator-masked, Parallel-group, Active-controlled, Randomised, Non-inferiority Study in Adult Patients With Moderate to Severe Dry Eye Disease Related to Keratitis or Keratoconjunctivitis

Conditions
-----------------
Dry Eye Syndromes

Intervention / Treatment
-----------------
* Device: Alocross 0.2% Unit Dose
* Device: Vismed


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient eligibility is determined according to the following criteria: Male or female patient aged 18 years or above. Patient using artificial tears for at least 3 months prior to the Screening visit. Patient experiencing at least 2 symptoms of ocular discomfort rated ≥23 mm on the 0 to 100 mm visual analogue scale (VAS) (among itching, eye dryness, sticky feeling, photophobia, pain, burning or stinging, sandy feeling or grittiness, or foreign body sensation) at Screening and Baseline visits. OSS score (sum of nasal and temporal interpalpebral conjunctival and corneal vital staining) ≥4 and ≤9 on a modified Oxford scale at Screening and Baseline visits in at least one eye. TBUT of ≤10 seconds at Screening and Baseline visits and/or Schirmer's tear test of ≥3 and ≤9 mm/5 min at Screening visit in the same eye that fulfil inclusion criteria #4. The patient has signed and dated a written informed consent form prior to the initiation of any study procedures. Exclusion Criteria: Any patient who meets any of the following criteria (in any eye) will not qualify for entry into the study: Ocular CFS score ≥4 on a modified Oxford scale Ocular hypertension or glaucoma requiring IOP-lowering medication(s) History of ocular trauma, infection or ocular inflammatory condition within the last 3 months before the screening visit. Severe blepharitis and/or severe meibomian gland disease Filamentary keratitis Any ocular surface anomaly not related to DED Active ocular infection or history of ocular allergy or ocular herpes Patient with only one sighted eye or with a best corrected distance visual acuity ≤1/10 Use of any topical ocular treatment other than study device during the study (all non-study topical ocular treatment(s) must be stopped at the screening visit) Onset of lid hygiene (whatever the method) less than 2 months before the Screening visit Use of topical corticosteroids one month before the Screening Visit Use of isotretinoin, ciclosporin, tacrolimus, sirolimus, pimecrolimus or ocular cauterisation procedures 2 months before the screening visit and throughout the study Use of VISMED® within 6 weeks prior to the screening visit Refractive surgery (e.g. LASIK, LASEK, PRK) within 6 months and/or any other ocular laser/surgery within 3 months prior to the screening visit and during the study Insertion of temporary punctal plug(s) within 2 months prior to the Screening visit or permanent occlusion of lacrimal puncta on one or both sides Known hypersensitivity to any of the components of the study device or investigational products Non-ocular History of severe systemic allergy Systemic disease not stabilised within 1 month prior to the screening visit (e.g. diabetes with glycaemia out of range, thyroid dysfunction) or judged by the investigator to be incompatible with the conduct of the study procedures or the interpretation of the study results Any change of systemic concomitant medication within the month before the screening visit or planned change during the study period, except paracetamol Pregnancy or lactation at the screening and/or Baseline visit. Women of childbearing potential not using a medically acceptable, highly effective method of birth control (such as hormonal implants, injectable or oral contraceptives together with condoms, some intrauterine devices, sexual abstinence or vasectomised partner) from the Baseline visit throughout the conduct of the study treatment periods and up to 2 weeks after the study end. Post-menopausal women (two years without menstruation) do not need to use any method of birth control. Participation in a clinical trial with an investigational substance within the past 30 days prior to Baseline visit. Participation in another clinical study at the same time as the present study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: PROSPECTIVE, MULTICENTRE, INVESTIGATOR-MASKED, PARALLEL-GROUP, ACTIVE-CONTROLLED, RANDOMISED, NON-INFERIORITY STUDY
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alocross<br>Cross-linked HA 0.2% + Aloe Vera 0.1% solution (N=40) Posology: One Drop in each eye 4 times daily for 84 days | Device: Alocross 0.2% Unit Dose<br>* Eye Drops<br>|
| Active Comparator: Vismed<br>HA 0.18% hyaluronic solution (N40) Posology: One Drop in each eye 4 times daily for 84 days | Device: Vismed<br>* Eye drops<br>* Other names: HA 0.18% hypotonic solution;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ocular surface staining (OSS) score between baseline and Day 28. | The primary endpoint of the study is the difference between patients treated with ALOCROSS® and patients treated with VISMED® in the change of ocular surface staining (OSS) score between baseline and D28. An OSS higher than 0 is considered to be abnormal and may be a sign of KCS. But scores of 1 or 2 can also represent a late staining artifact if interpretation of the fluorescein corneal staining pattern is delayed beyond 8 minutes. Because this could lead to a high level of misclassification, an abnormal OSS is defined as being a score of 3 or above. | Between Baseline and day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ocular surface staining (OSS) score between baseline and Day 84 | The difference between patients treated with ALOCROSS® and patients treated with VISMED® in change of OSS score between baseline and Day 84. An OSS higher than 0 is considered to be abnormal and may be a sign of KCS. But scores of 1 or 2 can also represent a late staining artifact if interpretation of the fluorescein corneal staining pattern is delayed beyond 8 minutes. Because this could lead to a high level of misclassification, an abnormal OSS is defined as being a score of 3 or above. | between baseline and Day 14 and between baseline and Day 84 | 
| The change of ocular stainings (corneal fluorescein staining (CFS) and clearing and conjunctival staining) between baseline and Day 28 and between baseline and Day 84 | The difference between patients treated with ALOCROSS® and patients treated with VISMED® in change of ocular stainings (corneal fluorescein staining (CFS) and clearing and conjunctival staining) Staining using fluorescein will be graded using the modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area [cornea + nasal and temporal conjunctiva]) for cornea and conjunctiva separately, On this modified scale, the score 0 corresponds to no staining dots and the score 0.5 corresponds to one staining dot per area. A CFS grade of 0 represents complete corneal clearing. | between baseline and Day 28 and between baseline and Day 84 | 
| The change of ocular discomfort symptoms on Visual Analogue Scale | The difference between patients treated with ALOCROSS® and patients treated with VISMED® in the change of ocular discomfort symptoms according to the Visual Analogue Scale (VAS) Patient experiencing at least 2 symptoms of ocular discomfort rated ≥23 mm on the 0 to 100 mm visual analogue scale (VAS) (among itching, eye dryness, sticky feeling, photophobia, pain, burning or stinging, sandy feeling or grittiness, or foreign body sensation) at Screening and Baseline visits. | between baseline and Day 28 and between baseline and Day 84 | 
| The change tear breakup time (TBUT) | The difference between patients treated with ALOCROSS® and patients treated with VISMED® in the change of tear breakup time (TBUT) Generally, >10 seconds is thought to be normal,(10, 11, 12) 5 to 10 seconds, marginal, and < 5 seconds is considered low. A short tear break-up time is a sign of a poor tear film and the longer it takes the more stable the tear film. | between baseline and Day 28 and between baseline and Day 84 | 
| The change in Schirmer's tear test | The difference between patients treated with ALOCROSS® and patients treated with VISMED® in the change of Schirmer's tear test Healthy eyes are considered to leave each strip of paper containing more than 10 millimeters of moisture. Less than 10 millimeters of moisture indicates probable dry eye syndrome. | between baseline and Day 28 and between baseline and Day 84 | 
| The secondary endpoints are the difference between patients treated with ALOCROSS® and patients treated with VISMED® in: | The overall efficacy evaluation of the investigator The study investigator at each centre will conduct an overall assessment of the effect of the study device on improvement in the patients DED using the following rating scale: 0 = Unsatisfactory 1 = Not very satisfactory 2 = Satisfactory 3 = Very satisfactory | after 12 weeks of treatment (84 days) | 
| The difference between patients treated with ALOCROSS® and patients treated with VISMED® in: | The change of subjective assessments evaluation by the patient. The patient will rate his global evaluation of efficacy using the same rating scale as the Investigator. The patients complete a subjective assessment of the effect of the study device on improvement in their DED using the following rating scale: 0 = Unsatisfactory 1 = Not very satisfactory 2 = Satisfactory 3 = Very satisfactory | between baseline and Day 84 |