Emerald: Phase 3 Study of OTX-101 in the Treatment of Keratoconjunctivitis Sicca

Sponsor
Sun Pharmaceutical Industries Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT02688556
Collaborator
(none)
745
Enrollment
3
Locations
2
Arms
10
Actual Duration (Months)
248.3
Patients Per Site
24.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-masked, vehicle-controlled study of the safety and efficacy of OTX-101 (0.09% cyclosporine nanomicellar solution) in the treatment of keratoconjunctivitis sicca to be conducted at approximately 50 sites.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
745 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Multicenter, Double-Masked, Vehicle-Controlled Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca
Actual Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Nov 1, 2016
Actual Study Completion Date :
Dec 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Experimental: OTX-101 0.09%

0.09% cyclosporine nanomicellar ophthalmic solution

Drug: cyclosporine
Other Names:
  • Seciera
  • Placebo Comparator: Vehicle

    vehicle of OTX-101

    Drug: vehicle of OTX-101

    Outcome Measures

    Primary Outcome Measures

    1. Tear Production [Baseline and 12 weeks]

      Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score

    Secondary Outcome Measures

    1. Conjunctival Staining [Baseline and 12 weeks]

      change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots)

    2. Central Corneal Staining [Baseline and 12 weeks]

      change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale.

    3. Symptom Score [Baseline and 12 weeks]

      change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • History of dry eye syndrome (KCS) for a period of at least 6 months

    • Clinical diagnosis of bilateral KCS

    • Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible score of 12 (scoring excludes superior zones 2 and 4) in the same eye at both the Screening and Baseline Visits.

    • Global symptom score (SANDE) ≥ 40 mm at both the Screening and Baseline Visits

    • Corrected Snellen visual acuity (VA) of better than 20/200 in each eye.

    Exclusion Criteria:
    • Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to the Screening Visit.

    • Previous treatment failure (lack of efficacy) with cyclosporine ophthalmic emulsion 0.05% (Restasis).

    • Diagnosis of Sjögren's disease ˃ 5 years prior to the Screening Visit.

    • Clinical diagnosis or any history of seasonal and/or perennial allergic conjunctivitis.

    • Use of systemic or topical medications within 7 days prior to the Screening Visit or during the study period that are known to cause dry eye.

    • Use of any topical ophthalmic medications, prescription (including anti-glaucoma medications) or over the counter (including artificial tears), other than the assigned study medication during the study period.

    • Current active eye disease other than dry wyw syndrome (i.e., any disease for which topical or systemic ophthalmic medication is necessary).

    • History of herpes keratitis.

    • Corneal transplant

    • Corneal refractive surgery within 6 months prior to the Screening Visit or postoperative refractive surgery symptoms of dryness that have not resolved.

    • Cataract surgery within 3 months prior to the Screening Visit.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Martel Eye Medical GroupRancho CordovaCaliforniaUnited States95670
    2Cincinnati Eye InstituteEdgewoodKentuckyUnited States41017
    3Fifth Avenue Eye AssociatesNew YorkNew YorkUnited States10028

    Sponsors and Collaborators

    • Sun Pharmaceutical Industries Limited

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sun Pharmaceutical Industries Limited
    ClinicalTrials.gov Identifier:
    NCT02688556
    Other Study ID Numbers:
    • OTX-101-2016-001
    First Posted:
    Feb 23, 2016
    Last Update Posted:
    Nov 19, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Sun Pharmaceutical Industries Limited
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailOne subject in OTX-101 0.09% group, was never treated with study medication and is not included in any of analysis sets Additionally, because the subjects in the ITT analysis set were analyzed as randomized, one subject who erroneously received OTX-101 0.09%, was included in the Vehicle group for purposes of efficacy analysis.
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101
    Period Title: Overall Study
    STARTED372373
    COMPLETED347361
    NOT COMPLETED2512

    Baseline Characteristics

    Arm/Group TitleOTX-101 0.09%VehicleTotal
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101Total of all reporting groups
    Overall Participants371373744
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.4
    (14.10)
    59.5
    (14.68)
    59.0
    (14.40)
    Sex: Female, Male (Count of Participants)
    Female
    315
    84.9%
    311
    83.4%
    626
    84.1%
    Male
    56
    15.1%
    62
    16.6%
    118
    15.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.3%
    0
    0%
    1
    0.1%
    Asian
    11
    3%
    12
    3.2%
    23
    3.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    0.3%
    1
    0.1%
    Black or African American
    41
    11.1%
    45
    12.1%
    86
    11.6%
    White
    310
    83.6%
    305
    81.8%
    615
    82.7%
    More than one race
    8
    2.2%
    10
    2.7%
    18
    2.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleTear Production
    DescriptionPercentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score
    Time FrameBaseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101
    Measure Participants371373
    Number [Percentage of eyes]
    16.6
    9.2
    2. Secondary Outcome
    TitleConjunctival Staining
    Descriptionchange from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots)
    Time FrameBaseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101
    Measure Participants371373
    Mean (Standard Deviation) [score on a scale]
    -1.53
    (1.927)
    -1.16
    (2.2064)
    3. Secondary Outcome
    TitleCentral Corneal Staining
    Descriptionchange from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale.
    Time FrameBaseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101
    Measure Participants341373
    Mean (Standard Deviation) [score on a scale]
    -0.28
    (0.533)
    -0.26
    (0.588)
    4. Secondary Outcome
    TitleSymptom Score
    Descriptionchange from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement.
    Time FrameBaseline and 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solutionvehicle of OTX-101
    Measure Participants371373
    Mean (Standard Deviation) [score on a scale]
    -18.8
    (24.08)
    -19.1
    (23.14)

    Adverse Events

    Time Frame12 weeks
    Adverse Event Reporting Description
    Arm/Group TitleOTX-101 0.09%Vehicle
    Arm/Group Description0.09% cyclosporine nanomicellar ophthalmic solution. A total of 744 subjects were included in the Safety population, with 372 subjects in the OTX-101 0.09% group and 372 subjects in the Vehicle group. The only difference between the ITT and the Safety populations is that Subject 14-003 was analyzed in the Safety population according to the treatment received, which was OTX-101 0.09%vehicle of OTX-101 A total of 744 subjects were included in the Safety population, with 372 subjects in the OTX-101 0.09% group and 372 subjects in the Vehicle group. The only difference between the ITT and the Safety populations is that Subject 14-003 was analyzed in the Safety population according to the treatment received, which was OTX-101 0.09%
    All Cause Mortality
    OTX-101 0.09%Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/372 (0.3%) 0/372 (0%)
    Serious Adverse Events
    OTX-101 0.09%Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/372 (1.6%) 2/372 (0.5%)
    General disorders
    Death1/372 (0.3%) 10/372 (0%) 0
    Perforated ulcer0/372 (0%) 01/372 (0.3%) 1
    Infections and infestations
    Pneumonia1/372 (0.3%) 10/372 (0%) 0
    Injury, poisoning and procedural complications
    Subdural haematoma1/372 (0.3%) 10/372 (0%) 0
    Musculoskeletal and connective tissue disorders
    Spinal column stenosis1/372 (0.3%) 10/372 (0%) 0
    Spinal osteoarthritis0/372 (0%) 01/372 (0.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant1/372 (0.3%) 10/372 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis1/372 (0.3%) 10/372 (0%) 0
    Other (Not Including Serious) Adverse Events
    OTX-101 0.09%Vehicle
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total130/372 (34.9%) 66/372 (17.7%)
    Eye disorders
    Conjunctival hyperaemia30/372 (8.1%) 18/372 (4.8%)
    Blepharitis5/372 (1.3%) 0/372 (0%)
    Eye irritation3/372 (0.8%) 5/372 (1.3%)
    Eye pruritus1/372 (0.3%) 5/372 (1.3%)
    Instillation site reaction4/372 (1.1%) 2/372 (0.5%)
    Sinusitis4/372 (1.1%) 5/372 (1.3%)
    Urinary tract infection4/372 (1.1%) 2/372 (0.5%)
    Foreign body sensation in eyes1/372 (0.3%) 5/372 (1.3%)
    Conjunctival haemorrhage2/372 (0.5%) 1/372 (0.3%)
    Posterior capsule opacification2/372 (0.5%) 2/372 (0.5%)
    Punctate keratitis2/372 (0.5%) 3/372 (0.8%)
    General disorders
    Instillation site pain90/372 (24.2%) 16/372 (4.3%)
    Instillation site lacrimation4/372 (1.1%) 0/372 (0%)
    Nervous system disorders
    Headache6/372 (1.6%) 2/372 (0.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleSPARC
    OrganizationSun Pharma Advanced Research Company Limited
    Phone+912266455645
    Emailclinical.trials@sparcmail.com
    Responsible Party:
    Sun Pharmaceutical Industries Limited
    ClinicalTrials.gov Identifier:
    NCT02688556
    Other Study ID Numbers:
    • OTX-101-2016-001
    First Posted:
    Feb 23, 2016
    Last Update Posted:
    Nov 19, 2021
    Last Verified:
    Nov 1, 2021