Lacripep™ in Subjects With Dry Eye Associated With Primary Sjögren's Syndrome
- Conditions
- Primary Sjögren SyndromeDry Eye
- Interventions
- Drug: 0.005% LacripepDrug: 0.01% LacripepDrug: Placebo
- Registration Number
- NCT03226444
- Lead Sponsor
- TearSolutions, Inc.
- Brief Summary
The objective of this study is to evaluate the efficacy and safety of two strengths of Lacripep™ ophthalmic solution versus placebo administered three times daily for four weeks in subjects with a diagnosis of Dry Eye associated with documented Primary Sjögren's Syndrome
- Detailed Description
This is a multi-center, randomized, placebo-controlled, double-masked, parallel-group study. Subjects will be randomized into three treatment groups: 0.005%, or 0.01% Lacripep™, or placebo in a 1:1:1 ratio.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 204
Subjects who meet the following criteria will be selected:
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Subjects who are age 18 years of age or older at the time of obtaining informed consent.
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Subjects with a documented prior history or current diagnosis of Primary Sjögren's Syndrome according the American-European Consensus Group Sjögren's Syndrome Criteria (Appendix 4; must meet either 4 out of 6 total criteria OR 3 out of 4 signs). Note: Subjects who are on systemic (oral) therapy for the treatment of Sjögren's Syndrome must be on stable systemic treatment defined as the same treatment for the immediately prior 90 days.
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Subjects with a history of dry eye-related ocular symptoms, and who have self-reported use of over the counter ocular wetting agents within the last 120 days.
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Subjects who meet the following criteria at both screening and Visit 2 (Randomization/Baseline) examinations:
- FCS total score ≥ 4 and < 15 in the NEI/Industry Workshop scale, (Appendix 6)
- Symptom Severity score of ≥ 40 using the SANDE questionnaire (Appendix 3)
- Anesthetized Schirmer test score ≤ 5 mm wetting/5 min
- LGCS total score ≥ 5 using the NEI/Industry Workshop scale (where 0=no staining) Note: Subjects must meet all 4 criteria and eligible scores for FCS, Anesthetized Schirmer and LGCS must be in at least one eye and it must be in the same eye at the time of the visit.
Subjects meeting any of the following criteria at the Visit 1 (Screening) or Visit 2 (Randomization/Baseline) visits will be excluded:
- Subjects with any active infectious ocular condition.
- Subjects who are monocular or have a BCVA, using corrective lenses if necessary, of +1.0 logMAR or worse as assessed by Early Treatment Diabetic Retinopathy Study (ETDRS).
- Subjects with ocular inflammatory conditions (e.g., conjunctivitis, keratitis, anterior blepharitis, etc.) not related to dry eye syndrome.
- Subjects with clinical evidence of cicatricial ocular surface disease, such as cicatricial ocular pemphigoid or Stevens Johnson syndrome.
- Subjects who cannot suspend the use of any topical eye medications (including topical cyclosporine) other than the investigational product during the run-in and the study treatment phase.
- Subjects who have used Restasis® (topical ophthalmic cyclosporine) or Xiidra® (topical ophthalmic lifitegrast) within 14 days prior to Visit 1.
- Subjects who in the study eye have fluorescein corneal staining (FCS) Total Score = 15 or a Score = 3 in the superior region per the NEI/Industry Workshop scale or subjects who have FCS with diffuse confluent staining, filaments or frank epithelial defects.
- Subjects who have active or have had an outbreak of herpetic keratitis within 365 days of Visit 1 or subjects who are on chronic oral antivirals for ocular herpetic disease.
- Subjects who cannot suspend the use of and abstain from contact lens use from the Screening Visit (Visit 1) to the end of the study (Visit 5).
- Subjects who have a history of collagen vascular disease, auto immune disease or rheumatic disease other than Primary Sjögren's Syndrome (e.g., Lupus, Rheumatoid Arthritis, etc.).
- Subjects who have a history of or current Anterior Membrane Dystrophy.
- Subjects who have had a corneal transplant or similar corneal surgery (DALK, DSEK, DMEK, etc.).
- Subjects who have used or anticipate use of amiodarone.
- Subjects who within 30 days prior to Visit 1 alter the dose or anticipate alterations to the dose of the following: tetracyclines, Omega 3's or 6's.
- Subjects who within 60 days prior to Visit 1 and for the duration of the study alter the dose or anticipate alterations to the dose of the following: anticholinergics, antidepressants, oral contraceptives, isotretinoin, oral systemic corticosteroids, oral systemic immunosuppressive agents.
- Subjects who within 30 days prior to Visit 1 and for the duration of the study use topical ocular antihistamines, ocular, inhaled or intranasal corticosteroids, topical or oral mast cell stabilizers, oral antihistamines, topical or nasal vasoconstrictors, topical ocular NSAIDs, topical ocular antibiotics or serum tears.
- Subjects who in the study eye have had cauterization of the punctum or alterations to (insertion or removal) punctal plug(s) within the past 14 days prior to Visit 1. Note: If a punctal plug in place at Visit 2 (Randomization/Baseline) and it is dislodged, the plug should be replaced as soon as possible.
- Subjects who, in the study eye, have had corneal refractive surgery (LASIK, PRK, RK).
- Subjects who in the study eye, have a history of any operative procedure on the ocular surface or eyelids within 365 days prior to Visit 1 or with a history of intraocular surgery within 90 days prior to Visit 1.
- Subjects who are pregnant or suspected to be pregnant and subjects who are breastfeeding or intend to breastfeed. Female subjects of childbearing potential are required to have a negative urine pregnancy test at screening, and must agree to use an acceptable method of contraception from the time of signing informed consent until the end of study visit. Medically acceptable contraception methods include intrauterine device; barrier methods such as diaphragm, condom, cap or sponge, used with a spermicide; or hormonal contraception.
- Subjects with any physical or mental impairment that would preclude participation and the ability to give informed consent.
- Subjects who have participated in a device or Investigational drug study or clinical trial within 30 days of Visit 1. Participation in another during this study is excluded for the duration of this study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.005% Lacripep 0.005% Lacripep 0.005% Lacripep ophthalmic solution 0.01% Lacripep 0.01% Lacripep 0.01% Lacripep ophthalmic solution placebo Placebo placebo solution
- Primary Outcome Measures
Name Time Method Change in Fluorescein Corneal Staining total score Changes at Week 4 from Baseline Mean change from Baseline/Randomization (Visit 2) to Day 28 (Visit 4) in Fluorescein Corneal Staining (FCS) total score \[National Eye Institute (NEI)/Industry Workshop 0-15 scale, 0-3 scale in each of 5 regions\] in the study eye.
- Secondary Outcome Measures
Name Time Method Changes in Tear Film Break Up Time (TFBUT) Changes at Week 4 from Baseline Changes in tear film break up time (TFBUT) from Randomization/Baseline (Visit 2) to Day 28 (Visit 4) in the study eye
Eye Dryness Changes at Week 4 from Baseline Mean change from Baseline/Randomization (Visit 2) to Day 28 (Visit 4) in Eye Dryness Score (0-100 VAS scale, OU) from Individual Symptom Assessments (Instantaneous)
Mean Scores for Individual Symptom Assessments (Reflective) Day 28 Mean Scores for six Individual Symptom Assessments (Reflective) at Day 28 (Visit 4). The individual reflective symptom assessment is assessed in 6 categories (Eye Dryness, Burning/Stinging, Foreign Body Sensation, Eye Discomfort, Eye Pain and Fluctuating Vision). An anchor in the middle at 50 mm representing their symptom severity at the last visit. The 50 mm scale to the left of the anchor located in the center of the scale will measure worsening symptoms (a negative value) and the 50 mm scale to the right of the anchor located in the center of the scale will measure improving symptoms (a positive value). The lower score represents greater severity.
Changes in SANDE-1 to Visit 4 Changes from Baseline to Day 28. Changes in Symptom Assessment in Dry Eye Questionnaires (SANDE) Version 1 global score from Randomization/Baseline (Visit 2) to Day 28 (Visit 4). SANDE Version 1 questionnaire contains two items measuring the frequency and severity of dry eye symptoms. Each item is assessed on a 100 mm visual analog scale from 0 (Rarely for frequency, Very mild for severity) to 100 mm (All the time for frequency, Very Severe for severity), with higher scores representing greater frequency/severity.
Mean Scores SANDE 2 Day 28 Mean Scores for Symptom Assessment in Dry Eye Questionnaires (SANDE) Version 2 global scores at day 28 (Visit 4). SANDE Version 2 questionnaire contains two items measuring the frequency and severity of dry eye symptoms.The 50 mm scale to the left of the anchor located in the center of the scale will measure improving symptoms (a negative value) and the 50 mm scale to the right of the anchor located in the center of the scale will measure worsening symptoms (a positive value).
Changes in Individual Symptom Assessments (Instantaneous) Changes at Baseline to Day 28 Changes in each of the 5 additional Individual Symptom Assessment (Instantaneous) from Randomization/Baseline (Visit 2) to Day 28 (Visit 4). The individual instantaneous symptom assessment is a questionnaire that uses a 0-100 mm visual analog scale to rate the severity of each ocular symptom for both eyes (OU). There are six categories (Eye Dryness, Burning/Stinging, Foreign Body Sensation, Eye Discomfort, Eye Pain and Fluctuating Vision). The higher score represents more severe symptoms.
Changes in FCS at Post-Treatment Baseline to Visit 5 / Day 42 Changes in Fluorescein Corneal Staining (FCS) from Randomization/Baseline (Visit 2) to the Post-Treatment Follow-Up Visit (day 42) in the study eye. The FCS assessment will be performed for each of the five sections (Central, Inferior, Superior, Temporal, and Nasal) on both eyes (study eye and fellow eye) using the National Eye Institute (NEI)/Industry Workshop scale. The staining in each of the 5 sections of the cornea is evaluated per the NEI score: Grades of 0, 1, 2, and 3 with higher grades representing greater severity.
Changes in LGCS Changes at Week 4 from Baseline Changes in Lissamine Green Conjunctival Staining (LGCS) from Randomization/Baseline (Visit 2) to Day 28 (Visit 4) in the study eye.
Changes in Anesthetized Schirmer test Changes at Week 4 from Baseline Change in Anesthetized Schirmer test from Randomization/Baseline (Visit 2) to Day 28 (Visit 4) in the study eye.
Changes in SANDE-1 to Visit 5 Baseline to Visit 5 / Day 42 Changes in Symptom Assessment in Dry Eye Questionnaires (SANDE) Version 1 global score from Randomization/Baseline (Visit 2) to the Post Treatment Follow-up visit (Day 42). SANDE Version 1 questionnaire contains two items measuring the frequency and severity of dry eye symptoms. Each item is assessed on a 100 mm visual analog scale from 0 (Rarely for frequency, Very mild for severity) to 100 mm (All the time for frequency, Very Severe for severity), with higher scores representing greater frequency/severity.
Changes in Individual Symptom Assessments (Instantaneous) from Baseline Visit 5 Baseline to Visit 5 Changes in six Individual Symptoms (Instantaneous) from Randomization/Baseline (Visit 2) to the Post-Treatment Follow-up Visit (Day 42). The individual instantaneous symptom assessment is a questionnaire that uses a 0-100 mm visual analog scale to rate the severity of each ocular symptom. There are six categories (Eye Dryness, Burning/Stinging, Foreign Body Sensation, Eye Discomfort, Eye Pain and Fluctuating Vision). The higher score represents more severe symptoms.
Mean Scores for SANDE-2 Visit 5 / Day 42 Mean Scores for Symptom Assessment in Dry Eye Questionnaires (SANDE) Version 2 global score at the Post-Treatment Follow-Up Visit (Day 42). SANDE Version 2 questionnaire contains two items measuring the frequency and severity of dry eye symptoms.The 50 mm scale to the left of the anchor located in the center of the scale will measure improving symptoms (a negative value) and the 50 mm scale to the right of the anchor located in the center of the scale will measure worsening symptoms (a positive value).
Mean Scores for six Individual Symptom Assessments (Reflective) Visit 5 / Day 42 Mean Scores for six Individual Symptom Assessments (Reflective) at the Post-Treatment Follow-Up Visit (Day 42). The individual reflective symptom assessment is assessed in 6 categories (Eye Dryness, Burning/Stinging, Foreign Body Sensation, Eye Discomfort, Eye Pain and Fluctuating Vision). The 50 mm scale to the left of the anchor located in the center of the scale will measure worsening symptoms (a negative value) and the 50 mm scale to the right of the anchor located in the center of the scale will measure improving symptoms (a positive value).
Changes in LCGS Anesthetized Schirmer test, TFBUT Baseline to Day 28 Changes in Lissamine Green Conjunctival Staining (LCGS) Anesthetized Schirmer test, tear film break up time (TFBUT) from Randomization/Baseline (Visit 2) to Day 28 (Visit 4) in the qualifying fellow eye.
Changes in FCS Baseline to Day 28 Mean change from Baseline/Randomization (Visit 2) to Day 28 (Visit 4) in Fluorescein Corneal Staining (FCS) total score \[National Eye Institute (NEI)/Industry Workshop 0-15 scale, 0-3 scale in each of 5 regions\] in the qualifying fellow eye.
Trial Locations
- Locations (35)
Bruce A. Segal, MD PA Private Practice
🇺🇸Delray Beach, Florida, United States
Orange County Ophthalmology
🇺🇸Garden Grove, California, United States
Lugene Eye Institute
🇺🇸Glendale, California, United States
Perez Eye Center
🇺🇸Tampa, Florida, United States
Clinical Eye Research of Boston
🇺🇸Winchester, Massachusetts, United States
Milton M. Hom, OD FAAO FACAA (Sc)
🇺🇸Azusa, California, United States
Wolstan & Goldberg Eye Associates
🇺🇸Torrance, California, United States
University of Alabama Eye Center
🇺🇸Birmingham, Alabama, United States
Martel Eye Medical Group
🇺🇸Rancho Cordova, California, United States
Doctor My Eyes / Stephen Cohen, OD, PC
🇺🇸Scottsdale, Arizona, United States
Bowden Eye & Associates
🇺🇸Jacksonville, Florida, United States
International Eye Associates, PA
🇺🇸Ormond Beach, Florida, United States
Eye Consultants of Atlanta
🇺🇸Atlanta, Georgia, United States
Chicago Cornea Consultants, Ltd.
🇺🇸Hoffman Estates, Illinois, United States
Cornea Consultants of Albany
🇺🇸Slingerlands, New York, United States
The Eye Care Institute
🇺🇸Louisville, Kentucky, United States
Cornerstone Eye Care, PA
🇺🇸High Point, North Carolina, United States
Minnesota Eye Consultants, P.A.
🇺🇸Bloomington, Minnesota, United States
University of Pennsylvania Scheie Eye Institute
🇺🇸Philadelphia, Pennsylvania, United States
Tauber Eye Center
🇺🇸Kansas City, Missouri, United States
Bergstrom Eye Research
🇺🇸Fargo, North Dakota, United States
Abrams Eye Center
🇺🇸Cleveland, Ohio, United States
The Eye Clinic of Texas, an affiliate of Houston Eye Associates
🇺🇸League City, Texas, United States
UTHSC Department of Ophthalmology
🇺🇸Memphis, Tennessee, United States
Vistar Eye Center
🇺🇸Roanoke, Virginia, United States
Midwest Cornea Associates, LLC
🇺🇸Indianapolis, Indiana, United States
University of Colorado Department of Ophthalmology
🇺🇸Aurora, Colorado, United States
Corneal Consultants of Colorado
🇺🇸Littleton, Colorado, United States
Ophthalmology Associates
🇺🇸Saint Louis, Missouri, United States
Black Hills Eye Institute
🇺🇸Rapid City, South Dakota, United States
Ophthalmic Surgeons & Consultants of Ohio; The Eye Center of Columbus
🇺🇸Columbus, Ohio, United States
Virginia Eye Consultants
🇺🇸Norfolk, Virginia, United States
Schwartz Laser Eye Center
🇺🇸Scottsdale, Arizona, United States
University of California, Berkeley, School of Optometry
🇺🇸Berkeley, California, United States
University of Virginia University Eye Center
🇺🇸Charlottesville, Virginia, United States