A Study to Assess the Safety and Efficacy of ECF843 vs Vehicle in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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The study was planned to be conducted in 2 parts: Part 1 to determine the efficacy and safety of ECF843 vs vehicle, followed by Part 2 with additional exploratory assessments of ECF843 vs Vehicle. Both parts of the study included a double-masked study design, with randomization stratified for subjects with Sjogren's Syndrome.

Detailed Description
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Part 1 of the study was a double-masked, randomized, parallel design in which participants were assigned to one of the following five treatment arms/groups in a ratio of 1:1:1:1:1. ECF843 0.45 mg/mL three times daily (TID) or vehicle ECF843 0.15 mg/mL TID or vehicle ECF843 vehicle TID ECF843 0.15 mg/mL twice daily (BID) or vehicle ECF843 vehicle BID The planned duration of double-masked treatment during Part 1 was 56 days. For subjects randomized to ECF843, the maximum drug exposure was up to 28 days. At some point during Part 1, all participants received vehicle. The study was terminated after completion of Part 1 and Part 2 of the study was not therefore initiated.

Official Title
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A Randomized, Double-masked, Multicenter Study to Evaluate the Safety and Efficacy of ECF843 vs Vehicle in Subjects With Dry Eye Disease

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: ECF843
* Other: ECF843 vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment Adult male or female subjects 18 years of age or older At least 6 months history of dry eye disease in both eyes Must use, or feel the need to use, artificial tears/gels/lubricants on a regular basis Composite corneal fluorescein staining score >= 4 (modified National Eye Institute (NEI) scale) in at least one eye Schirmer score >= 1 and =< 10 mm after 5 minutes in at least one eye Patients with Sjögren's Syndrome must have dry eye Exclusion Criteria: Ocular infection in either eye within 30 days prior to Screening Use of artificial tears, gels, lubricants within 4 hours of the Screening Visit Use of contact lenses in either eye within 14 days of Screening Uncontrolled ocular rosacea Clinically significant conjunctivochalasis in either eye Other Corneal conditions affecting the corneal structure Severe ocular conditions such as herpes, graft versus host disease, Stephen's Johnson Syndrome, sarcoidosis Currently active, or history of ocular allergies during the time of year the patient will be participating in the study Patients with current punctal plugs or punctal cauterization or occlusion Chronic medications (both over the counter and prescription) that have not been stable for at least 30 days prior to Screening. Use of Restasis®, Cequa®, or Xiidra® within 30 days prior to Screening Use of ocular, nasal, inhaled, or systemic corticosteroids within 30 days of Screening History of malignancy of any organ system within the past five years Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ECF843 0.45 mg/mL TID or vehicle (Part 1)<br>ECF843 0.45 mg/mL TID or vehicle (Part 1) | Drug: ECF843<br>* Topical ocular eye drop<br>Other: ECF843 vehicle<br>* Topical ocular eye drop<br>|
| Experimental: ECF843 0.15 mg/mL TID or vehicle (Part 1)<br>ECF843 0.15 mg/mL TID or vehicle (Part 1) | Drug: ECF843<br>* Topical ocular eye drop<br>Other: ECF843 vehicle<br>* Topical ocular eye drop<br>|
| Placebo Comparator: ECF843 vehicle TID (Part 1)<br>ECF843 vehicle TID (Part 1) | Other: ECF843 vehicle<br>* Topical ocular eye drop<br>|
| Experimental: ECF843 0.15 mg/mL BID or vehicle (Part 1)<br>ECF843 0.15 mg/mL BID or vehicle (Part 1) | Drug: ECF843<br>* Topical ocular eye drop<br>Other: ECF843 vehicle<br>* Topical ocular eye drop<br>|
| Placebo Comparator: ECF843 vehicle BID (Part 1)<br>ECF843 vehicle BID (Part 1) | Other: ECF843 vehicle<br>* Topical ocular eye drop<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change From Baseline in Symptom Assessment in Dry Eye (SANDE) Score | The SANDE uses a 100 mm visual analog scale (VAS) and asks the subject to score frequency and severity of their ocular discomfort over the past 24 hours by putting a vertical mark on two separate horizontal scoring lines. The frequency scoring line utilizes the anchors of 'Rarely' to 'All the Time', while the severity scoring line utilizes the anchors of 'Very Mildly' to 'Very Severely uncomfortable'. The SANDE questionnaire was completed through an electronic diary by the subject at the Screening Visit(s) of Part 1, and thereafter every evening before bedtime during the study. The overall SANDE score was calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranged from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. Negative change from baseline indicates improvement. | Up to 28 days (Baseline (BL) to end of randomized treatment) | 
| Part 1: Change From Baseline in Composite Corneal Fluorescein Staining Score | The degree of staining was based on the Corneal Fluorescein Modified NEI Scale. Each of the five regions (central (C), superior (S), inferior (I), temporal (T), and nasal (N)) were graded based on a scale of 0 to 4, with higher scores suggestive of higher degrees of corneal staining. After entry of the scores per region, the total or composite (sum) score for each eye was automatically calculated (maximum score = 20/eye). A (+1) was added to the sum score for any eye with the presence of filaments. | Up to 28 days (Baseline (BL) to end of randomized treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Change From Baseline in Central Corneal Fluorescein Staining | The degree of staining was based on the Corneal Fluorescein Modified NEI Scale. Central region was graded based on a scale of 0 to 4, with higher scores suggestive of higher degrees of corneal staining. | Up to 28 days (Baseline (BL) to end of randomized treatment) | 
| Part 1: Change From Baseline in Inferior Corneal Fluorescein Staining | The degree of staining was based on the Corneal Fluorescein Modified NEI Scale. Inferior region was graded based on a scale of 0 to 4, with higher scores suggestive of higher degrees of corneal staining. | Up to 28 days (Baseline (BL) to end of randomized treatment) | 
| Part 1: Percentage of Participants With Ocular and Non-ocular Treatment Emergent Adverse Events (AEs) | The number of treatment emergent ocular and non-ocular adverse events was reported categorically: Mild, Moderate, Severe. Treatment emergent adverse events (TEAEs) are adverse events started after the first administration of randomized study treatment or events present prior to start of the randomized treatment but increased in severity based on preferred term. | Up to 28 days (Baseline (BL) to end of randomized treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Eye, Sjogrens, dry eye syndrome (DES), Keratoconjunctivitis sicca (KCS), keratitis, Xerophthalmia, Sjögren's Syndrome, Sjogren's Syndrome