CyclASol for the Treatment of Moderate to Severe Dry-eye Disease (DED)

A Phase 2, Multi-center, Randomized, Double-masked, Placebo (Vehicle)-Controlled Clinical Study With an Open Label Comparator Arm to Assess the Efficacy, Safety and Tolerability of Topical CyclASol® for Treatment of Dry Eye Disease

The objective of this study was to compare the safety, efficacy, and tolerability of two different dose levels of CyclASol Ophthalmic Solutions to placebo (vehicle) and Restasis for the treatment of the signs and symptoms of Dry Eye Disease (DED).

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndromes
• Intervention / Treatment: Drug: Cyclosporine A; Drug: Placebo

Detailed Description

This phase 2 study explored the safety, efficacy and tolerability of two CyclASol concentrations as one drop twice daily versus vehicle (placebo). In addition to the masked vehicle control arm, an open-label comparator arm consisting of Restasis was included.

The study explored a range of signs and symptoms of DED to gain an understanding of the possible treatment effects in comparison to vehicle and estimation of effect sizes. In line with current treatment guidelines, the proposed phase 2 population consisted of patients suffering from moderate to severe DED.

The primary treatment comparisons in this study were between the two CyclASol concentrations versus vehicle for the sign variable total corneal fluorescein staining and the symptom variable dryness severity visual analogue scale at day 113. All other comparisons between treatments groups were considered secondary analyses.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • CYS-002 Investigational Site
  • Maine
    • Lewiston, Maine, United States, 04240
      • CYS-002 Investigational Site
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • CYS-002 Investigational Site
    • Quincy, Massachusetts, United States, 02169
      • CYS-002 Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Informed Consent Form and HIPAA (Health Insurance Portability and Accountability Act ) document
• Patient-reported history of dry eye in both eyes
• Current use of over-the-counter and/or prescription eye drops for dry eye symptoms
• Ability and willingness to follow instructions, including participation in all study assessments and visits

Exclusion Criteria:

• Women who are pregnant, nursing or planning a pregnancy
• Unwillingness to submit a blood pregnancy test at screening and at the last visit (or early termination visit) if of childbearing potential, or unwillingness to use acceptable means of birth control
• Clinically significant slit-lamp findings or abnormal lid anatomy at screening
• DED secondary to scarring or ocular or periocular malignancy
• History of herpetic keratitis
• Active ocular allergies or ocular allergies that are expected to be active during the study period
• Ongoing ocular or systemic infection at screening or baseline
• Wear of contact lenses within 3 months prior to screening or anticipated use of contact lenses during the study
• History of no response to previous topical Cyclosporine A and/or use of topical Cyclosporine A within 6 months prior to screening
• Intra-ocular surgery or ocular laser surgery within the previous 6 months, or have any planned ocular and/or lid surgeries over the study period
• Presence of an uncontrolled systemic disease
• Presence of a known allergy and/or sensitivity to the study drug or its components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CyclASol Ophthalmic Solution 1; Cyclosporine A solution (dose-level 1) in vehicle	Drug: Cyclosporine A; topical ocular, eye drops; Other Names: Ciclosporin, CsA
Experimental: CyclASol Ophthalmic Solution 2; Cyclosporine A solution (dose-level 2) in vehicle	Drug: Cyclosporine A; topical ocular, eye drops; Other Names: Ciclosporin, CsA
Placebo Comparator: Placebo Ophthalmic Solution; Vehicle only	Drug: Placebo; topical ocular, eye drops; Other Names: Excipient
Active Comparator: Restasis; Cyclosporine A 0.05% ophthalmic emulsion	Drug: Cyclosporine A; topical ocular, eye drops; Other Names: Ciclosporin, CsA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days	The primary analysis and objective of the study was to compare the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. The sign endpoint was the change from baseline in total corneal fluorescein staining at day 113. The cornea is divided into five regions: central, superior, inferior, nasal and temporal. Each region is graded from 0-3 based on the National Eye Institute scale, where 0 indicates no staining and 3 maximal staining. The total score is the sum of all these regions. The maximum score for each eye is 15.	Baseline to 113 Days
Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days	The primary analysis and objective of the study was to compare the the two CyclASol groups versus vehicle (all blinded treatment arms) for one sign and one symptom endpoint. The open label active comparator arm was not included in the primary analysis to reduce the number of comparisons. Furthermore, the open label character could have had an impact on patient reported outcomes. The symptom endpoint was the change from baseline in severity of dryness VAS at Day 113. Dryness severity was rated from 0 to 100%, where 0% corresponds to "no dryness" and 100% corresponds to "maximum dryness".	Baseline to 113 Days

Collaborators and Investigators

• Sponsor: Novaliq GmbH
• Investigators: Study Director: Sonja Kroesser, Dr.sc.hum., Novaliq GmbH

Publications and helpful links

General Publications

• Wirta DL, Torkildsen GL, Moreira HR, Lonsdale JD, Ciolino JB, Jentsch G, Beckert M, Ousler GW, Steven P, Krosser S. A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease. Ophthalmology. 2019 Jun;126(6):792-800. doi: 10.1016/j.ophtha.2019.01.024. Epub 2019 Jan 28.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 25, 2015
• First Posted (Estimate): December 1, 2015

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CYS-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO