Efficacy and Safety of Iota-Carrageenan Eye Drops (NCX-4240)

Study Overview
=================
Brief Summary
-----------------
This clinical investigation aims at demonstrating that NCX-4240 is effective and safe in decreasing the number of days where adenoviral conjunctivis is detected in the eye and in reducing the duration and/or the severity of the signs and symptoms of adenoviral conjunctivis

Detailed Description
-----------------
A multicenter, double masked, parallel, randomized 1:1 ratio clinical investigation comparing carrageenan eye drops (NCX 4240) versus placebo up to 21 days. Total expected number of patients: 148 Randomization: patients will be randomized 1:1 between: Group A: eye drops containing iota-carrageenan (NCX 4240), 1 drop in each eye 8 times/day for 7 days (mandatory) then at least 4 to 8 times/day for the next 14 days until Day 21 or Group B: ocular lubricant eye drop (carmellose 0.5% sterile solution) 1 drop in each eye 8 times/day for 7 days (Mandatory), then 4 to 8 times/day for the next 14 days until Day 21.

Official Title
-----------------
Evaluation of the Efficacy and Safety of Iota-Carrageenan Eye Drops (NCX-4240) Versus Placebo in Patients With Adenoviral Conjunctivis

Conditions
-----------------
Adenoviral Conjunctivitis

Intervention / Treatment
-----------------
* Drug: Iota-Carrageenan
* Drug: Carmellose


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: With uni-or bilateral acute adenoviral conjunctivis as diagnostised with adenoplus test Conjunctivis signs and symptoms in at least one eye AND positive adenoplus test in at least one eye whatever signs/symptoms and positive adenoplus test are from the same eye or not Exclusion Criteria: Negative results with adenoplus test in both eyes a suspected bacterial, fungal, herpes, chlamydia or acanthamoeba co-infection, based on clinical investigation

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eye drops containing Iota-Carrageenan<br>Eye drops 3.2mg/ml | Drug: Iota-Carrageenan<br>* One drop in each eye 8 times per day for 7 days (mandatory), then 4 to 8 times/day for the next 14 days until Day 21<br>* Other names: NCX-4240;|
| Placebo Comparator: Ocular Lubricant Eye Drops<br>Carmellose 0.5% sterile solution | Drug: Carmellose<br>* 1 drop in each eye 8 times/day for 7 days (mandatory), then 4 to 8 times/day for the next 14 days until day 21<br>* Other names: Placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral eradication time NCX 4240 versus Placebo | Comparison in time to viral eradication in NCX-4240 and the placebo groups (when virus load is 0 or BLD - below the limit of detection) from the tears as measured by Polymerase Chain Reaction (PCR) at each visit. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative PCR | 1) Quantitative PCR (qPCR) results at all clinical investigation timepoints 4) Global patient discomfort with Likert 4 points scales: no discomfort - minimal - moderate - severe discomfort, assessed every day in the Patient's diary 5) Ocular signs as assessed by the investigators at each visit and for both eyes | 21 days | 
| Impact on daily activities | Impact of the disease on daily activities as measured by the patient daily with a 4 points Likert scale (no - minimal - moderate - severe) 5) Ocular signs as assessed by the investigators at each visit and for both eyes: Degree of bulbar conjunctival injection/hyperaemia will be graded using the Mc Monnies grading scale for conjunctival hyperaemia Other signs will be assessed with Likert 5 points scales: none - traces - mild - moderate - severe for chemosis (conjunctival edema), follicles, petechiae, and keratitis. Presence/absence of loco-regional lymphadenopathies will also be recorded | 21 days | 
| Patient discomfort | Global patient discomfort with Likert 4 points scales: no discomfort - minimal - moderate - severe discomfort, assessed every day in the Patient's diary | 21 days | 
| bulbar conjuntival infection | Ocular signs as assessed by the investigators at each visit and for both eyes: degree of bulbar conjunctival infection/hyperaemia will be graded using the McMonnies grading scale for conjunctival hypereaemia. | 21 days | 
| Other signs to be assessed | Ocular signs as assessed by the investigators at each visit and for both eyes: - Other signs will be assessed with Likert 5 points scales: none - traces - mild - moderate - severe for chemosis (conjunctival edema), follicles, petechiae, and keratitis. | 21 days | 
| loco-regional lymphadenopathies | Ocular signs as assessed by the investigators at each visit and for both eyes: Presence/absence of loco-regional lymphadenopathies | 21 days | 
| Ocular symptoms assessed by patients | Ocular symptoms as assessed by the patients in the patient diary: self-rated daily for 21 days: symptoms sum-score of pain, foreign body sensation, itchy eye(s), photophobia/light sensitivity, ocular secretions and eyelash matting. Assessments will be performed with Likert 5 points scales (none - traces - mild - moderate - severe). | 21 days | 
| Disease impact on daily activities | Impact of the disease on daily activities as measured by the patient daily with a 4 points Likert scale (no - minimal - moderate - severe) | 21 days | 
| Global patient discomfort | Global patient discomfort with Likert 4 points scales: no discomfort - minimal - moderate - severe discomfort, assessed every day in the Patient's diary | 21 days | 
| Adenoplus test results | AdenoPlus® test results, testing the studied eye at each post baseline visits. | 21 days | 
| Investigator's assessment of Membranes and pseudomembranes development | For both eyes: Development of membranes, pseudomembranes assessed by the investigator, incidence and severity (none - mild - moderate - severe) | 21 days | 
| Investigator's assessment of Membranes and pseudomembranes development | For both eyes: timing of occurrence if any | 21 days | 
| Investigator's assessment of Subepithelial Corneal Infiltrates development | For both eyes: Development of subepithelial corneal infiltrates (none - mild - moderate - severe) as assessed by the investigator | 21 days | 
| Investigator's assessment of Subepithelial Corneal Infiltrates development | For both eyes: Development of subepithelial corneal infiltrates: timing of occurrence as assessed by the investigator examination | 21 days | 
| Assessment of Incidence and severity of fellow eye signs and symptoms | If only one eye is affected (signs and symptoms) at baseline, assessment of the incidence and severity of the other eye signs and symptoms by the investigator | 21 days | 
| BCVA | Best corrected far Visual Acuity for both eyes (Day 1, 7, 14 and Day 21). | 21 days | 
| Global assessment of patient's satisfaction | Global assessment of the patient's satisfaction with the eye drops use with a 4 points Likert scale: poor, fair, good, excellent, will be performed at Day 7, 14 and 21 | 21 days | 
| Adverse events | Safety parameters (Adverse Events/Serious Adverse Events) | 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenoviral conjunctivis, iota-carrageenan