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

Primary Purpose

Dry Eye

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
LME636 ophthalmic solution
LME636 Vehicle
Sponsored by
Alcon, a Novartis Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye focused on measuring LME636, dry eye disease, efficacy, ocular discomfort

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    LME636

    Vehicle

    Arm Description

    LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks

    LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    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.
    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.
    Percentage of Subjects With Anti-LME636 Antibodies by Visit
    Samples were collected and assessed for anti-LME636 antibodies.

    Full Information

    First Posted
    February 13, 2015
    Last Updated
    May 31, 2018
    Sponsor
    Alcon, a Novartis Company
    Collaborators
    Novartis Institutes for BioMedical Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02365519
    Brief Title
    LME636 in the Relief of Persistent Ocular Discomfort in Subjects With Severe Dry Eye Disease
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    March 9, 2015 (Actual)
    Primary Completion Date
    October 16, 2015 (Actual)
    Study Completion Date
    October 16, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Alcon, a Novartis Company
    Collaborators
    Novartis Institutes for BioMedical Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dry Eye
    Keywords
    LME636, dry eye disease, efficacy, ocular discomfort

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    514 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    LME636
    Arm Type
    Experimental
    Arm Description
    LME636 ophthalmic solution, 1 drop (approx. 40 µL; 2.4 mg) administered topically in each eye 3 times a day (TID) for 6 weeks
    Arm Title
    Vehicle
    Arm Type
    Placebo Comparator
    Arm Description
    LME636 Vehicle, 1 drop administered topically in each eye TID for 6 weeks
    Intervention Type
    Biological
    Intervention Name(s)
    LME636 ophthalmic solution
    Intervention Type
    Biological
    Intervention Name(s)
    LME636 Vehicle
    Intervention Description
    Inactive ingredients used as a placebo comparator
    Primary Outcome Measure Information:
    Title
    Mean Change From Baseline in Global Ocular Discomfort Score at Day 71
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 71
    Title
    Best Corrected Visual Acuity (BCVA)
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 57, Day 71, Day 85
    Title
    Intraocular Pressure (IOP)
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 57, Day 71, Day 85
    Title
    Percentage of Subjects With Increase in Slit-Lamp Parameter From Baseline to Any Visit
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 57, Day 71, Day 85
    Title
    Percentage of Subjects With Increase in Dilated Fundus Parameter From Baseline to Any Visit
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 57, Day 71, Day 85
    Secondary Outcome Measure Information:
    Title
    Percentage of Subjects With More Than 20 Units Improvement in Global Ocular Discomfort Score From Baseline at Day 71
    Description
    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.
    Time Frame
    Baseline (Day 43), Day 71
    Title
    Percentage of Subjects With LME636 Serum Concentrations Below the Lower Limit of Quantification (LLOQ)
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. LLOQ is defined as 0.25 ng/mL.
    Time Frame
    Day 15, Day 29, Day 43, Day 57, Day 71, Day 85
    Title
    Percentage of Subjects With Anti-LME636 Antibodies by Visit
    Description
    Samples were collected and assessed for anti-LME636 antibodies.
    Time Frame
    Day 15, Day 29, Day 43, Day 57, Day 71, Day 85

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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. 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Senior Clinical Manager, GCRA
    Organizational Affiliation
    Alcon, A Novartis Division
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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