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

Phase 2

Completed

• Conditions: Dry Eye
• Interventions: Other: ECF843 vehicle; Drug: ECF843

• Registration Number: NCT04391894
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-05-13
• Study First Submitted QC: 2020-05-13
• Study First Posted: 2020-05-18
• Study Start: 2020-10-06
• Primary Completion: 2021-05-13
• Study Completion: 2021-05-13
• Results First Submitted: 2022-05-03
• Results First Submitted QC: 2022-05-03
• Results First Posted: 2022-05-26
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-27
• Last Update Posted: 2023-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 558

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ECF843 vehicle TID (Part 1)	ECF843 vehicle	ECF843 vehicle TID (Part 1)
ECF843 0.45 mg/mL TID or vehicle (Part 1)	ECF843	ECF843 0.45 mg/mL TID or vehicle (Part 1)
ECF843 0.45 mg/mL TID or vehicle (Part 1)	ECF843 vehicle	ECF843 0.45 mg/mL TID or vehicle (Part 1)
ECF843 vehicle BID (Part 1)	ECF843 vehicle	ECF843 vehicle BID (Part 1)
ECF843 0.15 mg/mL TID or vehicle (Part 1)	ECF843 vehicle	ECF843 0.15 mg/mL TID or vehicle (Part 1)
ECF843 0.15 mg/mL BID or vehicle (Part 1)	ECF843	ECF843 0.15 mg/mL BID or vehicle (Part 1)
ECF843 0.15 mg/mL BID or vehicle (Part 1)	ECF843 vehicle	ECF843 0.15 mg/mL BID or vehicle (Part 1)
ECF843 0.15 mg/mL TID or vehicle (Part 1)	ECF843	ECF843 0.15 mg/mL TID or vehicle (Part 1)

Primary Outcome Measures

Name	Time	Method
Part 1: Change From Baseline in Composite Corneal Fluorescein Staining Score	Up to 28 days (Baseline (BL) to end of randomized treatment)	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.
Part 1: Change From Baseline in Symptom Assessment in Dry Eye (SANDE) Score	Up to 28 days (Baseline (BL) to end of randomized treatment)	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.

Secondary Outcome Measures

Name	Time	Method
Part 1: Percentage of Participants With Ocular and Non-ocular Treatment Emergent Adverse Events (AEs)	Up to 28 days (Baseline (BL) to end of randomized treatment)	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.
Part 1: Change From Baseline in Central Corneal Fluorescein Staining	Up to 28 days (Baseline (BL) to end of randomized treatment)	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.
Part 1: Change From Baseline in Inferior Corneal Fluorescein Staining	Up to 28 days (Baseline (BL) to end of randomized treatment)	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 Seattle, Washington, United States