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

• Sponsor: Novaliq GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02617667
• Collaborator: (none)
• Enrollment: 207
• Locations: 4
• Arms: 4
• Duration (Months): 8
• Patients Per Site: 51.8
• Patients Per Site Per Month: 6.5

Study Details

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
• 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: Jan 1, 2016
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Sep 1, 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 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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	CYS-002 Investigational Site	Newport Beach	California	United States	92663
2	CYS-002 Investigational Site	Lewiston	Maine	United States	04240
3	CYS-002 Investigational Site	Andover	Massachusetts	United States	01810
4	CYS-002 Investigational Site	Quincy	Massachusetts	United States	02169

Sponsors and Collaborators

• Novaliq GmbH

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Publication of study results

Publications

None provided.

• Responsible Party: Novaliq GmbH
• ClinicalTrials.gov Identifier: NCT02617667
• Other Study ID Numbers: CYS-002
• First Posted: Dec 1, 2015
• Last Update Posted: Nov 6, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Cyclosporine; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	CyclASol 0.05% Ophthalmic Solution	CyclASol 0.1% Ophthalmic Solution	Placebo Ophthalmic Solution	Restasis
Arm/Group Description	Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily	Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.	Active comparator, open label arm. Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.
Period Title: Overall Study
STARTED	51	51	52	53
COMPLETED	50	50	48	52
NOT COMPLETED	1	1	4	1

Baseline Characteristics

Arm/Group Title	CyclASol 0.05% Ophthalmic Solution	CyclASol 0.1% Ophthalmic Solution	Placebo Ophthalmic Solution	Restasis	Total
Arm/Group Description	Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.	Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.	Total of all reporting groups
Overall Participants	51	51	52	53	207
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.3 (10.72)	61.1 (12.29)	61.3 (10.45)	62.8 (11.20)	62.4 (11.36)
Sex: Female, Male (Count of Participants)
Female	38 74.5%	36 70.6%	39 75%	40 75.5%	153 73.9%
Male	13 25.5%	15 29.4%	13 25%	13 24.5%	54 26.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Visit 1) in Total Corneal Fluorescein Staining at 113 Days
Description	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.
Time Frame	Baseline to 113 Days

Outcome Measure Data

Analysis Population Description

Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was selected as the worst eye.

Arm/Group Title	CyclASol 0.05% Ophthalmic Solution	CyclASol 0.1% Ophthalmic Solution	Placebo Ophthalmic Solution
Arm/Group Description	Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.
Measure Participants	51	51	52
Mean (Standard Deviation) [units on a scale]	-2.38 (2.156)	-2.10 (2.252)	-1.69 (2.619)

2. Primary Outcome

Title	Change From Baseline (Visit 1) in Dryness Severity Visual Analog Scale (VAS) at 113 Days
Description	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".
Time Frame	Baseline to 113 Days

Outcome Measure Data

Analysis Population Description

Full analysis set population for worst eye. Worst eye: Eyes were eligible for analysis if they met all inclusion criteria. If both eyes qualified, the worst eye was taken as the eye with higher (worse) staining at Visit 1. If staining was the same, the right eye was taken.

Arm/Group Title	CyclASol 0.05% Ophthalmic Solution	CyclASol 0.1% Ophthalmic Solution	Placebo Ophthalmic Solution
Arm/Group Description	Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.	Blinded treatment arm. Vehicle only. Topical ocular eye drops. 1 drop in each eye, twice daily.
Measure Participants	51	51	52
Mean (Standard Deviation) [units on a scale]	-11.00 (19.362)	-9.30 (27.832)	-13.85 (25.301)

Adverse Events

Time Frame	Adverse events reported were documented from the first dose of randomized study drug until the end of the last study day visit (day 113)
Arm/Group Title	CyclASol 0.05% Ophthalmic Solution		CyclASol 0.1% Ophthalmic Solution		Placebo Ophthalmic Solution		Restasis
Arm/Group Description	Blinded treatment arm. Cyclosporine A solution (0.05%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.		Blinded treatment arm. Cyclosporine A solution (0.1%) in vehicle. Topical ocular eye drops. 1 drop in each eye, twice daily.		Blinded treatment arm. Vehicle only Topical ocular eye drops. 1 drop in each eye, twice daily.		Active comparator, open label arm . Cyclosporine A 0.05% ophthalmic emulsion topical ocular eye drops. 1 drop in each eye, twice daily.
All Cause Mortality
	CyclASol 0.05% Ophthalmic Solution		CyclASol 0.1% Ophthalmic Solution		Placebo Ophthalmic Solution		Restasis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/51 (0%)		0/52 (0%)		0/53 (0%)
Serious Adverse Events
	CyclASol 0.05% Ophthalmic Solution		CyclASol 0.1% Ophthalmic Solution		Placebo Ophthalmic Solution		Restasis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/51 (3.9%)		0/51 (0%)		0/52 (0%)		1/53 (1.9%)
Cardiac disorders
Acute coronary syndrome	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/53 (0%)	0
Myocardial infarction	1/51 (2%)	1	0/51 (0%)	0	0/52 (0%)	0	0/53 (0%)	0
Reproductive system and breast disorders
Ovarian Cyst	0/51 (0%)	0	0/51 (0%)	0	0/52 (0%)	0	1/53 (1.9%)	1
Other (Not Including Serious) Adverse Events
	CyclASol 0.05% Ophthalmic Solution		CyclASol 0.1% Ophthalmic Solution		Placebo Ophthalmic Solution		Restasis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.8%)		4/51 (7.8%)		4/52 (7.7%)		4/53 (7.5%)
Eye disorders
Visual acuity reduced	2/51 (3.9%)	2	4/51 (7.8%)	6	1/52 (1.9%)	2	4/53 (7.5%)	6
Infections and infestations
Nasopharyngitis	3/51 (5.9%)	3	0/51 (0%)	0	3/52 (5.8%)	3	0/53 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.