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

• ClinicalTrials.gov Identifier: NCT02617667
• Recruitment Status: Completed
• First Posted: December 1, 2015
• Results First Posted: July 26, 2018
• Last Update Posted: November 6, 2019
• Sponsor: Novaliq GmbH
• Information provided by (Responsible Party): Novaliq GmbH

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Dry Eye Syndromes	Drug: Cyclosporine A; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2016
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days [ Time Frame: Baseline to 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.
2. Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days [ Time Frame: Baseline to 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".

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

CYS-002 Investigational Site

Newport Beach, California, United States, 92663

United States, Maine

CYS-002 Investigational Site

Lewiston, Maine, United States, 04240

United States, Massachusetts

CYS-002 Investigational Site

Andover, Massachusetts, United States, 01810

CYS-002 Investigational Site

Quincy, Massachusetts, United States, 02169

Sponsors and Collaborators

Novaliq GmbH

Investigators

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

More Information

Additional Information:

Publication of study results 

Publications of Results:

Wirta DL, Torkildsen GL, Moreira HR, Lonsdale JD, Ciolino JB, Jentsch G, Beckert M, Ousler GW, Steven P, Krösser 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.

• Responsible Party: Novaliq GmbH
• ClinicalTrials.gov Identifier: NCT02617667
• Other Study ID Numbers: CYS-002
• First Posted: December 1, 2015
• Results First Posted: July 26, 2018
• Last Update Posted: November 6, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Cyclosporine; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors