Dry EyePhase 2NCT02365519

LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease

A Phase 2 study testing LME636 ophthalmic solution in people with Dry Eye, run by Alcon, a Novartis Company.

Completed

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

Trial summary

The purpose of this study is to evaluate the efficacy of LME636 compared to vehicle in the reduction of ocular symptoms and to evaluate the safety and tolerability of LME636, when administered topically for up to 42 days, in subjects with severe dry eye disease. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Dry Eye
What is being tested?: LME636 ophthalmic solution
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 514 participants
Where: No sites listed yet
Study dates: 9 Mar 2015to 16 Oct 2015
Phase: Phase 2
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

Must sign written informed consent.
Physician diagnosis of DED of at least 6 months prior to Visit 1.
Must use artificial tears, gels, lubricants or re-wetting drops on a regular basis.
Respond as "often" or "constantly" to the question "How often do your eyes feel uncomfortable?".
Best Corrected Visual Acuity (BCVA) of 55 or greater in each eye as measured by ETDRS at Visit 1.
Other protocol-specified inclusion criteria may apply.

Who cannot join

Presence of any acute infection or non-infectious ocular condition in either eye within 1 month of Visit 1.
Contact lens wearers, defined as individuals who cannot be without their contact lenses for the entire duration of the study.
Any chronic ocular degenerative condition that in the opinion of the Investigator could possibly advance during the time course of the study.
Use of biologics treatments, such as systemic biologic anti-cytokines, including anti-TNFα drugs, or immunosuppressive therapy for the treatment of severe systemic autoimmune disorders.
Diseases or conditions affecting the ocular surface that are associated with clinically significant scarring and or destruction of conjunctiva and/or cornea.
Unwilling to abstain from topical ocular non-prescription medications during the course of the study, including concomitant use of artificial tears, gels, lubricants, re-wetting drops, allergy drops, etc. after Visit 2.

Show all 9Show fewer

Use of nasal, inhaled, systemic (including injections), or topical corticosteroids within 30 days of Visit 1.
Women of child-bearing potential unwilling to use effective contraception methods as defined in the protocol.
Other protocol-specified exclusion criteria may apply.

About this study

Official title: A Randomized, Double-masked, Vehicle-controlled Study of LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease

Read the detailed description

This study is organized into 2 phases. Following a 2-week identification phase, eligible subjects with severe dry eye disease (DED) will be randomized into the treatment phase and will be dispensed study treatment for 10 weeks.

Conditions: Dry Eye
Being tested: LME636 ophthalmic solution, LME636 Vehicle
Keywords: LME636, dry eye disease, efficacy, ocular discomfort
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.

LME636 ophthalmic solutionBiological
LME636 VehicleBiological
Inactive ingredients used as a placebo comparator

Study groups in NCT02365519
Study group	Role	What they receive
LME636	Experimental	LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks Receives: Biological: LME636 ophthalmic solution
Vehicle	Placebo comparator	LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks Receives: Biological: LME636 Vehicle

What is being measured

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

Mean Change From Baseline in Global Ocular Discomfort Score at Day 71
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement.
Measured: Baseline (Day 43), Day 71
Best Corrected Visual Acuity (BCVA)
Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an ETDRS visual acuity chart at 3 meters (10 feet) and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Both eyes contributed to the analysis.
Measured: Baseline (Day 43), Day 57, Day 71, Day 85
Intraocular Pressure (IOP)
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Both eyes contributed to the analysis.
Measured: Baseline (Day 43), Day 57, Day 71, Day 85
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Ocular signs (cornea, lens, and iris/anterior chamber) were assessed by slit-lamp biomicroscopy. An increase indicates worsening. Only one eye contributed to the analysis.
Measured: Baseline (Day 43), Day 57, Day 71, Day 85
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
The dilated fundus examination was performed to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. An increase indicates worsening. Only one eye contributed to the analysis.
Measured: Baseline (Day 43), Day 57, Day 71, Day 85

Secondary outcomes (3)

Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a VAS displayed on a handheld ePRO. Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline.
Measured: Baseline (Day 43), Day 71
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL.
Measured: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Samples were collected and assessed for anti-LME636 antibodies.
Measured: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85

Timeline

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

9 Mar 201516 Oct 2015

First posted19 Feb 2015 (estimated)
Study start9 Mar 2015
Primary completion16 Oct 2015
Study completion16 Oct 2015

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.
Other trials for Dry EyeStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 514 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02365519
Sponsor's protocol ID: LME636-2202
Status last verified: Oct 2017
First submitted: 13 Feb 2015
Last updated: 2 Jul 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

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?

Official record

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All Dry Eye trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-masked, Vehicle-controlled Study of LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease
ClinicalTrials.gov ID: NCT02365519
Acronym / sponsor ID: LME636-2202
Conditions: Dry Eye
Keywords: LME636, dry eye disease, efficacy, ocular discomfort
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 514 participants (actual)
Lead sponsor: Alcon, a Novartis CompanyIndustry (pharma, biotech, devices)
Collaborators: Novartis Institutes for BioMedical Research
Study start: 9 Mar 2015 (actual)
Primary completion: 16 Oct 2015 (actual)
Study completion: 16 Oct 2015 (actual)
First posted: 19 Feb 2015 (estimated)
Results: Posted 24 Nov 2017

Clinical summary

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

Detailed description

Study design

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

Arm	Type	Receives
LME636	Experimental	Biological: LME636 ophthalmic solutionLME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks
Vehicle	Placebo comparator	Biological: LME636 VehicleLME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks

Who may qualify

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

Key inclusion criteria (6 listed)

Must sign written informed consent.
Physician diagnosis of DED of at least 6 months prior to Visit 1.
Must use artificial tears, gels, lubricants or re-wetting drops on a regular basis.
Respond as "often" or "constantly" to the question "How often do your eyes feel uncomfortable?".
Best Corrected Visual Acuity (BCVA) of 55 or greater in each eye as measured by ETDRS at Visit 1.

Key exclusion criteria (9 listed)

Presence of any acute infection or non-infectious ocular condition in either eye within 1 month of Visit 1.
Contact lens wearers, defined as individuals who cannot be without their contact lenses for the entire duration of the study.
Any chronic ocular degenerative condition that in the opinion of the Investigator could possibly advance during the time course of the study.
Use of biologics treatments, such as systemic biologic anti-cytokines, including anti-TNFα drugs, or immunosuppressive therapy for the treatment of severe systemic autoimmune disorders.
Diseases or conditions affecting the ocular surface that are associated with clinically significant scarring and or destruction of conjunctiva and/or cornea.

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
LME636 ophthalmic solution	Biological	LME636
LME636 VehicleInactive ingredients used as a placebo comparator	Biological	Vehicle

Primary outcome

Mean Change From Baseline in Global Ocular Discomfort Score at Day 71
Time frame: Baseline (Day 43), Day 71
Discomfort frequency and severity (each graded on a separate 100-units scale) were assessed daily using a visual analog scale (VAS) displayed on a handheld digital Pad (electronic patient-reported outcome (ePRO)). Frequency score was in response to the question 'how often your eyes felt uncomfortable during the past 24 hours' ranging from 'Rarely' to 'All the time.' Severity score was in response to the question 'how uncomfortable your eyes felt during the past 24 hours' ranging from 'Very mildly uncomfortable' to 'Very severely uncomfortable.' The Global Ocular Discomfort Score, ranging from 0 to 100, was calculated for any given day, as the square root of the product of the discomfort frequency score multiplied by the discomfort severity score. Improvement results in a reduction of the discomfort frequency or severity, or both, translating into a reduction of the resulting Global Ocular Discomfort score as compared to baseline. A negative change from baseline indicates improvement.
Best Corrected Visual Acuity (BCVA)
Time frame: Baseline (Day 43), Day 57, Day 71, Day 85
Visual Acuity (VA) with the subject's best spectacles or other visual corrective devices was measured using an ETDRS visual acuity chart at 3 meters (10 feet) and reported in letters read correctly. An increase (gain) in letters read indicates improvement. Both eyes contributed to the analysis.
Intraocular Pressure (IOP)
Time frame: Baseline (Day 43), Day 57, Day 71, Day 85
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry or Tonopen and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Both eyes contributed to the analysis.
Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
Time frame: Baseline (Day 43), Day 57, Day 71, Day 85
Ocular signs (cornea, lens, and iris/anterior chamber) were assessed by slit-lamp biomicroscopy. An increase indicates worsening. Only one eye contributed to the analysis.
Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
Time frame: Baseline (Day 43), Day 57, Day 71, Day 85
The dilated fundus examination was performed to evaluate the health of the vitreous, retina, macula, choroid, and optic nerve. An increase indicates worsening. Only one eye contributed to the analysis.

3 secondary outcomes

Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71
Time frame: Baseline (Day 43), Day 71
Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
Time frame: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85
Percentage of Subjects With Anti-LME636 Antibodies by Visit
Time frame: Day 15, Day 29, Day 43, Day 57, Day 71, Day 85

Results and safety

Results posted to the registry on 24 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vehicle Run-In	213	134
LME636	0	0
Vehicle	0	0

Primary outcome: Mean Change From Baseline in Global Ocular Discomfort Score at Day 71

Time frame: Baseline (Day 43), Day 71. Mean (Standard Error). Unit: units on a scale

Measure	LME636 n = 67	Vehicle n = 64
Value	-7.9 (1.45)	-3.6 (1.49)

Population analysed: This analysis population includes all randomized subjects with at least a post-baseline primary endpoint assessment excluding all subjects who met the critical deviation criteria (Per-Protocol Set). Number Analyzed is the number of subjects with data at visit.

Primary outcome: Best Corrected Visual Acuity (BCVA)

Time frame: Baseline (Day 43), Day 57, Day 71, Day 85. Mean (Standard Deviation). Unit: letters

Measure	LME636 n = 69	Vehicle n = 65
Baseline (Day 43)	80.6 (6.44)	81.5 (5.72)
Day 57	80.5 (6.82)	81.6 (5.48)
Day 71	81.6 (5.56)	81.9 (5.89)
Day 85	81.0 (5.73)	81.6 (6.17)

Population analysed: This analysis population includes all subjects that received any study drug (Safety Analysis Set). Number Analyzed is the number of subjects with data at visit.

Primary outcome: Intraocular Pressure (IOP)

Time frame: Baseline (Day 43), Day 57, Day 71, Day 85. Mean (Standard Deviation). Unit: mmHg

Measure	LME636 n = 69	Vehicle n = 65
Baseline (Day 43)	14.8 (2.71)	14.3 (2.63)
Day 57	14.6 (2.72)	14.1 (2.92)
Day 71	14.0 (3.06)	14.1 (2.70)
Day 85	14.4 (2.68)	14.6 (2.58)

Population analysed: Safety Analysis Set. Number Analyzed is the number of subjects with data at visit.

Primary outcome: Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit

Time frame: Baseline (Day 43), Day 57, Day 71, Day 85. Number. Unit: percentage of subjects

Measure	LME636 n = 69	Vehicle n = 65
Cornea	0.0	0.0
Lens	0.0	0.0
Iris	0.0	0.0
Anterior Chamber	0.0	0.0

Population analysed: Safety Analysis Set

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were collected from time of informed consent for the duration of a subject's participation in the study (up to 85 days).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vehicle Run-In	1 of 213 (0.5%)	0 of 213 (0%)	0 of 213
LME636	0 of 69 (0%)	0 of 69 (0%)	0 of 69
Vehicle	1 of 65 (1.5%)	0 of 65 (0%)	0 of 65

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Dry Eye

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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.

Senior Clinical Manager, GCRA study director

Alcon, A Novartis Division

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LME636 ophthalmic solution in people with Dry Eye, run by Alcon, a Novartis Company.

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 6 inclusion and 9 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 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 24 Nov 2017). 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?

Mean Change From Baseline in Global Ocular Discomfort Score at Day 71 (time frame: Baseline (Day 43), Day 71). The study lists 5 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 NCT02365519.

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 2 Jul 2018.