Dry Eye Disease
Conditions
Brief summary
SURF-100 is being studied for the treatment of dry eye disease. SURF-100 is an investigational drug (which means the study drug is currently being tested) in the form of a sterile eye drop. The purpose of this research study is to see how well SURF-100 works to treat dry eye and what potential side effects there are, and to compare it with Vehicle (placebo), 0.1% mycophenolic acid (MPA) in Vehicle, 0.3% MPA in Vehicle, 0.01% betamethasone phosphate (BSP) in Vehicle, Restasis and Xiidra. This study will involve about 280-350 study participants age 18 and older at about 40 different research sites in the United States.
Interventions
DRUGSURF-100 (Combination of 0.3% Mycophenolic Acid and 0.01% Betamethasone Sodium Phosphate)
combination of a topical immunosuppressant and a topical corticosteroid solution
DRUGMycophenolic Acid 0.1%
topical immunosuppressant
DRUGMycophenolic Acid 0.3%
topical immunosuppressant
DRUGBetamethasone Sodium Phosphate 0.01%
topical corticosteroid solution
topical vehicle solution
topical ophthalmic emulsion
topical ophthalmic solution
Sponsors
Surface Ophthalmics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults at least 18 years of age at the time of the Screening visit. 2. Willing and able to read, sign, and date the informed consent form (ICF) after the nature of the study has been explained and any questions have been answered, and prior to initiation of any study procedures or exams. 3. Willing and able to comply with all study procedures and attend all study visits. 4. Willing to suspend use of tear substitutes at least 72 hours prior to Visit 2 (Day 0) through Visit 7 (Day 98). 5. Best corrected visual acuity (BCVA) of 0.7 log of the minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1 (Day -14 to Day 0). 6. Subject-reported history of dry eye in both eyes. 7. Meeting ALL of the following criteria in the same eye at Visit 1 (Day -14 to Day 0) and meeting ALL of the following criteria in the same eye at Visit 2 (Day 0) if Visit 2 is performed \>5 days after Visit 1: 1. Minimum score of greater than or equal to 5 but less than or equal to 9 on UNC DEMS questionnaire. 2. Schirmer Tear Test (with anesthesia) equal to or less than 10 mm, but more than 1 mm. 3. TBUT: Equal to or less than 5 seconds 8. A negative urine pregnancy test if female and of childbearing potential (those who are not surgically sterilized \[bilateral tubal ligation, hysterectomy, or bilateral oophorectomy\] or post-menopausal \[12 months after last menses\] or premenarchal) and must have used adequate birth control throughout the study period (through Visit 7 \[Day 98\]). Adequate birth control is defined as hormonal-oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as condom or diaphragm; intrauterine device; abstinence; or surgical sterilization of male partner. 9. Subjects with secondary Sjögren's syndrome (e.g., rheumatoid arthritis, systemic lupus erythematosus) or other autoimmune diseases (e.g., multiple sclerosis, inflammatory bowel disease) are eligible for study consideration provided the subject meets all other inclusion and
Exclusion criteria
, AND are not in a medical state - in the opinion of the principal investigator - that could interfere with study parameters, are not taking systemic/ocular steroids, and are not immunodeficient/immunosuppressed (e.g., receiving systemic immunomodulating or immunosuppressive drugs to manage their baseline medical state).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | Baseline and Day 84 | The UNC DEMS scale is a participant-specific 10-point scale with a minimum score of 1 (\[1-2\] My symptoms are not a problem. My dry eye does not affect my daily life at all) and a maximum score of 10 (\[9-10\] my symptoms are severe and I need immediate medical care. My dry eye greatly affects my daily life). Participants with a 10% or higher reduction in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tear Break Up Time (TBUT), Study Eye | Baseline and Day 84 | The absolute change from baseline in TBUT in the study eye at Day 84. |
| Schirmer Tear Test Score, Study Eye | Baseline and Day 84 | The absolute change from baseline in Schirmer tear score in the study eye at Day 84. |
Countries
United States
Participant flow
Pre-assignment details
Prior to each participant's assignment by chance to one of the seven treatment arms/groups (randomization), the Investigator designated the participant's Study Eye. The participant's Study Eye was the eye that was eligible for the study and had the worst signs and symptoms. The participant's other eye was called the Fellow Eye.
Participants by arm
| Arm | Count |
|---|---|
| SURF-100 Eye drop:
Topical, preservative-free SURF-100 (a combination of 0.3% mycophenolic acid and 0.01% betamethasone sodium phosphate)
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 52 |
| SURF-100 Eye drop:
Topical, preservative-free SURF-100 (a combination of 0.3% mycophenolic acid and 0.01% betamethasone sodium phosphate)
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 52 |
| Mycophenolic Acid 0.1% Eye drop:
Topical, preservative-free mycophenolic acid 0.1%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 50 |
| Mycophenolic Acid 0.1% Eye drop:
Topical, preservative-free mycophenolic acid 0.1%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 50 |
| Mycophenolic Acid 0.3% Eye drop:
Topical preservative-free mycophenolic acid 0.3%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 50 |
| Mycophenolic Acid 0.3% Eye drop:
Topical preservative-free mycophenolic acid 0.3%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 50 |
| Betamethasone Sodium Phosphate 0.01% Eye drop:
Topical preservative free betamethasone sodium phosphate 0.01%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 49 |
| Betamethasone Sodium Phosphate 0.01% Eye drop:
Topical preservative free betamethasone sodium phosphate 0.01%
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 49 |
| Placebo Comparator: Vehicle Eye drop:
Topical preservative-free placebo comparator (vehicle)
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 47 |
| Placebo Comparator: Vehicle Eye drop:
Topical preservative-free placebo comparator (vehicle)
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 47 |
| Cyclosporine 0.05% Ophthalmic Emulsion Eye drop:
Topical preservative-free cyclosporine 0.05% ophthalmic emulsion
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 47 |
| Cyclosporine 0.05% Ophthalmic Emulsion Eye drop:
Topical preservative-free cyclosporine 0.05% ophthalmic emulsion
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 47 |
| Lifitegrast 5% Ophthalmic Solution Eye drop:
Topical, preservative-free lifitegrast 5% ophthalmic solution
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 54 |
| Lifitegrast 5% Ophthalmic Solution Eye drop:
Topical, preservative-free lifitegrast 5% ophthalmic solution
Dosing: One drop in the study eye (and fellow eye, if applicable) twice daily for 84 days. | 54 |
| Total | 698 |
Baseline characteristics
| Characteristic | Lifitegrast 5% Ophthalmic Solution | Total | SURF-100 | Mycophenolic Acid 0.1% | Mycophenolic Acid 0.3% | Betamethasone Sodium Phosphate 0.01% | Placebo Comparator: Vehicle | Cyclosporine 0.05% Ophthalmic Emulsion |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 14.53 | 61.7 years STANDARD_DEVIATION 14.42 | 61.4 years STANDARD_DEVIATION 14.16 | 61.4 years STANDARD_DEVIATION 16.29 | 60.3 years STANDARD_DEVIATION 14.34 | 61.8 years STANDARD_DEVIATION 13.92 | 60.7 years STANDARD_DEVIATION 14.75 | 63.2 years STANDARD_DEVIATION 13.41 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 18 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 31 Participants | 7 Participants | 2 Participants | 1 Participants | 6 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 44 Participants | 291 Participants | 40 Participants | 42 Participants | 47 Participants | 41 Participants | 41 Participants | 36 Participants |
| Schirmer Tear Test (with Anesthesia), Study Eye | 5.5 millimeters STANDARD_DEVIATION 2.38 | 5.5 millimeters STANDARD_DEVIATION 2.47 | 5.7 millimeters STANDARD_DEVIATION 2.48 | 5.1 millimeters STANDARD_DEVIATION 2.42 | 5.2 millimeters STANDARD_DEVIATION 2.54 | 5.8 millimeters STANDARD_DEVIATION 2.7 | 5.6 millimeters STANDARD_DEVIATION 2.34 | 5.4 millimeters STANDARD_DEVIATION 2.48 |
| Sex: Female, Male Female | 41 Participants | 265 Participants | 37 Participants | 35 Participants | 39 Participants | 44 Participants | 35 Participants | 34 Participants |
| Sex: Female, Male Male | 13 Participants | 84 Participants | 15 Participants | 15 Participants | 11 Participants | 5 Participants | 12 Participants | 13 Participants |
| Tear Break-up Time (TBUT), Study Eye | 3.43 seconds STANDARD_DEVIATION 0.88 | 3.5 seconds STANDARD_DEVIATION 0.88 | 3.43 seconds STANDARD_DEVIATION 0.98 | 3.60 seconds STANDARD_DEVIATION 0.87 | 3.41 seconds STANDARD_DEVIATION 0.91 | 3.39 seconds STANDARD_DEVIATION 0.87 | 3.62 seconds STANDARD_DEVIATION 0.83 | 3.36 seconds STANDARD_DEVIATION 0.78 |
| University of North Carolina Dry Eye Management Scale (UNC DEMS) Score at Baseline | 6.9 UNC DEMS units STANDARD_DEVIATION 1.32 | 6.9 UNC DEMS units STANDARD_DEVIATION 1.2 | 7.1 UNC DEMS units STANDARD_DEVIATION 1.13 | 6.9 UNC DEMS units STANDARD_DEVIATION 1.23 | 6.7 UNC DEMS units STANDARD_DEVIATION 1.33 | 6.7 UNC DEMS units STANDARD_DEVIATION 1.11 | 7.0 UNC DEMS units STANDARD_DEVIATION 1.19 | 6.8 UNC DEMS units STANDARD_DEVIATION 1.07 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 50 | 0 / 50 | 0 / 49 | 0 / 47 | 0 / 47 | 0 / 54 |
| other Total, other adverse events | 10 / 52 | 10 / 50 | 9 / 50 | 3 / 49 | 6 / 47 | 6 / 47 | 20 / 54 |
| serious Total, serious adverse events | 1 / 52 | 0 / 50 | 1 / 50 | 0 / 49 | 0 / 47 | 1 / 47 | 0 / 54 |
Outcome results
Primary
University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis
The UNC DEMS scale is a participant-specific 10-point scale with a minimum score of 1 (\[1-2\] My symptoms are not a problem. My dry eye does not affect my daily life at all) and a maximum score of 10 (\[9-10\] my symptoms are severe and I need immediate medical care. My dry eye greatly affects my daily life). Participants with a 10% or higher reduction in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group.
Time frame: Baseline and Day 84
Population: Intent-to Treat Analysis Population: Includes all randomized subjects. Missing values were imputed using last observation carried forward (LOCF).~LOCF: common statistical approach to the analysis of longitudinal repeated measures where some follow-up \[FU\] observations may be missing.~In a LOCF analysis, a missing FU value is replaced by/imputed as that participant's previously observed value. The combination of the observed and imputed data is then analyzed as if there were no missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SURF-100 | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 65.4 percentage of responders |
| Mycophenolic Acid 0.1% | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 90.0 percentage of responders |
| Mycophenolic Acid 0.3% | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 66.0 percentage of responders |
| Betamethasone Sodium Phosphate 0.01% | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 71.4 percentage of responders |
| Placebo Comparator: Vehicle | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 80.9 percentage of responders |
| Cyclosporine 0.05% Ophthalmic Emulsion | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 72.3 percentage of responders |
| Lifitegrast 5% Ophthalmic Solution | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 57.4 percentage of responders |
Comparison: Exploratory Phase 2 Study; the sample size of approximately 280-350 subjects (between 40 and 50 subjects per each of the 7 treatment groups) was based on medical judgement.p-value: 0.004Fisher Exact
Secondary
Schirmer Tear Test Score, Study Eye
The absolute change from baseline in Schirmer tear score in the study eye at Day 84.
Time frame: Baseline and Day 84
Population: Intent-to Treat (ITT) Analysis Population: It included all randomized subjects regardless of whether a study medication was taken. Missing data were not imputed. For subjects who were withdrawn from the study prior to study completion, all data compiled up to the point of subject withdrawal from the study was used for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SURF-100 | Schirmer Tear Test Score, Study Eye | 3.20 millimeters |
| Mycophenolic Acid 0.1% | Schirmer Tear Test Score, Study Eye | 2.94 millimeters |
| Mycophenolic Acid 0.3% | Schirmer Tear Test Score, Study Eye | 4.46 millimeters |
| Betamethasone Sodium Phosphate 0.01% | Schirmer Tear Test Score, Study Eye | 1.66 millimeters |
| Placebo Comparator: Vehicle | Schirmer Tear Test Score, Study Eye | 3.98 millimeters |
| Cyclosporine 0.05% Ophthalmic Emulsion | Schirmer Tear Test Score, Study Eye | 2.25 millimeters |
| Lifitegrast 5% Ophthalmic Solution | Schirmer Tear Test Score, Study Eye | 2.73 millimeters |
Comparison: MMRM analysis included fixed effects of baseline Schirmer test score, age, treatment, visit, and treatment by visit interaction.~LSMs of the absolute change from baseline in Schirmer test score and their 95% CIs were estimated from the MMRM model for each treatment group.p-value: 0.2027Fisher Exact
Secondary
Tear Break Up Time (TBUT), Study Eye
The absolute change from baseline in TBUT in the study eye at Day 84.
Time frame: Baseline and Day 84
Population: Intent-to Treat Analysis Population: It included all randomized subjects regardless of whether a study medication was taken. Missing data were not imputed. For subjects who were withdrawn from the study prior to study completion, all data compiled up to the point of subject withdrawal from the study was used for analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SURF-100 | Tear Break Up Time (TBUT), Study Eye | 1.70 seconds |
| Mycophenolic Acid 0.1% | Tear Break Up Time (TBUT), Study Eye | 1.84 seconds |
| Mycophenolic Acid 0.3% | Tear Break Up Time (TBUT), Study Eye | 1.41 seconds |
| Betamethasone Sodium Phosphate 0.01% | Tear Break Up Time (TBUT), Study Eye | 2.56 seconds |
| Placebo Comparator: Vehicle | Tear Break Up Time (TBUT), Study Eye | 1.12 seconds |
| Cyclosporine 0.05% Ophthalmic Emulsion | Tear Break Up Time (TBUT), Study Eye | 2.40 seconds |
| Lifitegrast 5% Ophthalmic Solution | Tear Break Up Time (TBUT), Study Eye | 1.52 seconds |
Comparison: Mixed Model for Repeated Measures (MMRM) analysis included fixed effects of baseline TBUT, age, treatment, visit, and treatment by visit interaction.~Least squares means (LSMs) of the absolute TBUT change from baseline and their 95% CIs were estimated from the MMRM model for each treatment group.p-value: 0.3111Fisher Exact