Dry Eye DiseasePhase 3NCT04523129

ESSENCE 2: CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (DED)

A Phase 3 study testing CyclASol topical ocular, eye drops in people with Dry Eye Disease, run by Novaliq GmbH at 27 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this pivotal trial is to assess the efficacy, safety and tolerability of CyclASol in comparison to the vehicle for the treatment of signs and symptoms of Dry Eye Disease (DED). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Dry Eye Disease
What is being tested?: CyclASol topical ocular, eye drops
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 834 participants
Where: 27 sitesUnited States
Study dates: 5 Dec 2020to 8 Oct 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed ICF (Informed Consent Form)
Patient-reported history of DED in both eyes
Current use of OTC (over-the-counter) and/or artificial tears for dry eye symptoms
Ability and willingness to follow instructions, including participation in all study assessments and visits

Who cannot join

Women who are pregnant, nursing or planning a pregnancy
Unwillingness to submit a urine pregnancy test at screening and 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
Ocular/periocular malignancy
History of herpetic keratitis
Active ocular allergies or ocular allergies that may become active during the study period

Show all 13Show fewer

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
Use of topical Cyclosporine A or Liftigrast within 2 months prior to screening
Intraocular 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 uncontrolled systemic diseases
Presence of known allergy and/or sensitivity to the study drug or its components
Randomized in a previous CyclASol trial

Trial locations and contacts

27 sites in 1 country.

City, postcode or hospital

27 sites in 1 country

United States27 sites

CYS-004 Investigational Site
Andover, Massachusetts, 01810
CYS-004 Investigational Site
Carmel, Indiana, 46290
CYS-004 Investigational Site
Chicago, Illinois, 60619
CYS-004 Investigational Site
Colorado Springs, Colorado, 80907
CYS-004 Investigational Site
Cranberry Township, Pennsylvania, 16066
CYS-004 Investigational Site
Fargo, North Dakota, 58103
CYS-004 Investigational Site
Fort Lauderdale, Florida, 33309
CYS-004 Investigational Site
Henderson, Nevada, 89052
CYS-004 Investigational Site
Indianapolis, Indiana, 46240
CYS-004 Investigational Site
Kansas City, Missouri, 64111
CYS-004 Investigation Site
Kansas City, Missouri, 64154
CYS-004 Investigational Site
Layton, Utah, 84041
CYS-004 Investigational Site
Los Angeles, California, 90013
CYS-004 Investigational site
Louisville, Kentucky, 40206
CYS-004 Investigational Site
Lynchburg, Virginia, 24502
CYS-004 Investigational Site
Medina, Minnesota, 55364
CYS-004 Investigational Site
Memphis, Tennessee, 38119
CYS-004 Investigational Site
Newport Beach, California, 92663
CYS-004 Investigational site
Ogden, Utah, 84403
CYS-004 Investigational Site
Phoenix, Arizona, 85032
CYS-004 Investigational Site
Raleigh, North Carolina, 27603
CYS-004 Investigational Site
Raynham, Massachusetts, 02767
CYS-004 Investigational Site
Santa Ana, California, 92705
CYS-004 Investigational Site
Seattle, Washington, 98119
CYS-004 Investigational Site
Shelby, North Carolina, 28150
CYS-004 Investigational Site
Smyrna, Tennessee, 37167
CYS-004 Investigational Site
Warwick, Rhode Island, 02886

Other trials in United States

About this study

Official title: A Phase 3, Multi-center, Randomized, Double-masked, Vehicle-controlled Clinical Trial to Assess the Efficacy and Safety of Topical CyclASol® for the Treatment of Dry Eye Disease

The objective of this pivotal trial is to assess the efficacy, safety and tolerability of CyclASol in comparison to the vehicle for the treatment of signs and symptoms of Dry Eye Disease (DED).

Read the detailed description

This Phase 3 study will assess the efficacy, safety and tolerability of CyclASol 0.1% Ophthalmic Solution administered bilaterally twice daily versus vehicle.

Conditions: Dry Eye Disease
Being tested: CyclASol topical ocular, eye drops, Vehicle topical ocular, eye drops
Medical subject headings: Dry Eye Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CyclASol topical ocular, eye dropsDrug
Also called Ciclosporine (CSA)
Cyclosporine A solution in vehicle
Vehicle topical ocular, eye dropsDrug
Also called Vehicle
Vehicle

Study groups in NCT04523129
Study group	Role	What they receive
CyclASol Ophthalmic Solution	Experimental	Cyclosporine A solution in vehicle Receives: Drug: CyclASol topical ocular, eye drops
Vehicle Ophthalmic solution	Placebo comparator	Vehicle only Receives: Drug: Vehicle topical ocular, eye drops

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Total Corneal Fluorescein Staining
Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst).
Measured: baseline and 1 month [day 29]
Change From Baseline in Eye Dryness Score
Eye dryness score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort.
Measured: baseline and 1 month [day 29]

Secondary outcomes (6)

Change From Baseline in Total Conjunctival Lissamine Green Staining
Conjunctival staining was assessed by the investigator in the nasal and temporal sections. The Oxford Scheme was used for each section, with a possible score of 0-5 for each section, where 0=absent and 5=severe. The nasal and temporal scores were summed, for a possible score of 0-10 for each eye.
Measured: baseline and 1 month [day 29]
Proportion of Responders in Central Corneal Fluorescein Staining Score
≥ 1 score improvement for cCFS on National Eye Institute (NEI) scale: Central Corneal Fluorescein Staining (cCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst).
Measured: baseline and 1 month [day 29]
Proportion of Responders in Total Corneal Fluorescein Staining Score
≥ 3 scores improvement for tCFS on National Eye Insititute (NEI) scale: Total Corneal Fluorescein Staining (tCFS) is graded based on the NEI scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) -15 (worst).
Measured: baseline and 1 month [day 29]
Change From Baseline in Central Corneal Fluorescein Staining
Central Corneal Fluorescein Staining (cCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst).
Measured: baseline and 1 month [day 29]
Change From Baseline in Total Corneal Fluorescein Staining
Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst).
Measured: baseline and 2 weeks [day 15]
Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision
Blurred vision score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort.
Measured: baseline and 1 month [day 29]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Dec 20208 Oct 2021

First posted21 Aug 2020
Study start5 Dec 2020
Primary completion3 Sep 2021
Study completion8 Oct 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Dry Eye DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 834 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04523129
Sponsor's protocol ID: CYS-004
Status last verified: Mar 2023
First submitted: 19 Aug 2020
Last updated: 10 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Akpek EK, Wirta DL, Downing JE, Tauber J, Sheppard JD, Ciolino JB, Meides AS, Krosser S. Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial. JAMA Ophthalmol. 2023 May 1;141(5):459-466. doi: 10.1001/jamaophthalmol.2023.0709.
PubMed 37022717

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 10 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Multi-center, Randomized, Double-masked, Vehicle-controlled Clinical Trial to Assess the Efficacy and Safety of Topical CyclASol® for the Treatment of Dry Eye Disease
ClinicalTrials.gov ID: NCT04523129
Acronym / sponsor ID: CYS-004
Conditions: Dry Eye Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 834 participants (actual)
Lead sponsor: Novaliq GmbHIndustry (pharma, biotech, devices)
Study start: 5 Dec 2020 (actual)
Primary completion: 3 Sep 2021 (actual)
Study completion: 8 Oct 2021 (actual)
First posted: 21 Aug 2020 (actual)
Results: Posted 10 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The objective of this pivotal trial is to assess the efficacy, safety and tolerability of CyclASol in comparison to the vehicle for the treatment of signs and symptoms of Dry Eye Disease (DED).

Detailed description

This Phase 3 study will assess the efficacy, safety and tolerability of CyclASol 0.1% Ophthalmic Solution administered bilaterally twice daily versus vehicle.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
CyclASol Ophthalmic Solution	Experimental	Drug: CyclASol topical ocular, eye dropsCyclosporine A solution in vehicle
Vehicle Ophthalmic solution	Placebo comparator	Drug: Vehicle topical ocular, eye dropsVehicle only

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Signed ICF (Informed Consent Form)
Patient-reported history of DED in both eyes
Current use of OTC (over-the-counter) and/or artificial tears for dry eye symptoms
Ability and willingness to follow instructions, including participation in all study assessments and visits

Key exclusion criteria (13 listed)

Women who are pregnant, nursing or planning a pregnancy
Unwillingness to submit a urine pregnancy test at screening and 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
Ocular/periocular malignancy
History of herpetic keratitis

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CyclASol topical ocular, eye dropsAlso: Ciclosporine (CSA)Cyclosporine A solution in vehicle	Drug	CyclASol Ophthalmic Solution
Vehicle topical ocular, eye dropsAlso: VehicleVehicle	Drug	Vehicle Ophthalmic solution

Primary outcome

Change From Baseline in Total Corneal Fluorescein Staining
Time frame: baseline and 1 month [day 29]
Total Corneal Fluorescein Staining (tCFS) is graded based on the National Eye Institute (NEI) scale. The NEI scale divides the cornea in 5 subregions: central, inferior, superior, nasal, temporal. The score for each region ranges from 0-3; 0 corresponds to no staining (best), 3 corresponds to maximum staining (worst). The total score is the sum of the 5 subregions ranging from 0 (best) - 15 (worst).
Change From Baseline in Eye Dryness Score
Time frame: baseline and 1 month [day 29]
Eye dryness score is rated on a visual analogue scale (VAS) ranging from 0-100; 0 corresponds to no discomfort and 100 to maximum discomfort.

6 secondary outcomes

Change From Baseline in Total Conjunctival Lissamine Green Staining
Time frame: baseline and 1 month [day 29]
Proportion of Responders in Central Corneal Fluorescein Staining Score
Time frame: baseline and 1 month [day 29]
Proportion of Responders in Total Corneal Fluorescein Staining Score
Time frame: baseline and 1 month [day 29]
Change From Baseline in Central Corneal Fluorescein Staining
Time frame: baseline and 1 month [day 29]
Change From Baseline in Total Corneal Fluorescein Staining
Time frame: baseline and 2 weeks [day 15]
Change From Baseline in Visual Analogue Scale (VAS) for Blurred Vision
Time frame: baseline and 1 month [day 29]

Results and safety

Results posted to the registry on 10 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CyclASol Ophthalmic Solution	423	415
Vehicle Ophthalmic Solution	411	402

Primary outcome: Change From Baseline in Total Corneal Fluorescein Staining

Time frame: baseline and 1 month [day 29]. Least squares mean (Standard Error). Unit: score on a scale

Measure	CyclASol Ophthalmic Solution n = 409	Vehicle Ophthalmic Solution n = 395
Value	-3.96 (0.146)	-3.55 (0.149)

Primary outcome: Change From Baseline in Eye Dryness Score

Time frame: baseline and 1 month [day 29]. Least squares mean (Standard Error). Unit: score on a scale

Measure	CyclASol Ophthalmic Solution n = 409	Vehicle Ophthalmic Solution n = 395
Value	-12.2 (1.29)	-13.6 (1.31)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was were collected over the study period (29 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CyclASol Ophthalmic Solution	2 of 423 (0.5%)	45 of 423 (10.6%)	0 of 423
Vehicle Ophthalmic Solution	3 of 411 (0.7%)	37 of 411 (9%)	0 of 411

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37022717Akpek EK, Wirta DL, Downing JE, Tauber J, Sheppard JD, Ciolino JB, Meides AS, Krosser S. Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial. JAMA Ophthalmol. 2023 May 1;141(5):459-466. doi: 10.1001/jamaophthalmol.2023.0709.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sonja Kroesser, PhD study director

Novaliq GmbH

27 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CyclASol topical ocular, eye drops in people with Dry Eye Disease, run by Novaliq GmbH at 27 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Total Corneal Fluorescein Staining (time frame: baseline and 1 month [day 29]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04523129, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.