Dry Eye Disease
Conditions
Brief summary
SURF-200 is being studied in people experiencing an episodic flare-up of their dry eye disease. SURF-200 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-200 works and what side effects there are, and to compare it with vehicle (placebo). The study will involve about 120 study participants at multiple research sites in the United States.
Interventions
DRUG0.02% Betamethasone Sodium Phosphate
topical corticosteroid solution
DRUG0.04% Betamethasone Sodium Phosphate
topical corticosteroid solution
DRUGPlacebo
topical vehicle 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. Subjects 18 years of age and older who have a diagnosis of dry eye disease and experiencing an episodic flare up. Criteria for the diagnosis must include the following: 1. UNC DEMS score of greater than or equal to 5 but less than or equal to 9 2. Conjunctival hyperemia score of greater than or equal to 2 in the study eye when using the conjunctival hyperemia reference photos 3. Schirmer's Tear Test score (with anesthesia) greater than 1 mm but less than or equal to12 mm in the study eye 2. Subjects must be able to understand and sign the Informed Consent Form (ICF). 3. Female subjects of childbearing potential must agree to and submit a negative urine pregnancy test before any study-specific procedures are performed. The subjects must be using and continue to use a suitable method of contraception for the duration of the study: spermicide with barrier, oral contraceptive, transdermal contraceptive, injectable or implantable contraceptive, intrauterine device (IUD), abstinence or surgical sterilization of a partner. If a subject is not of childbearing potential (e.g., has been postmenopausal for at least 12 months or is premenarchal, or has undergone a hysterectomy, bilateral oophorectomy or a bilateral tubal ligation), a urine pregnancy test and use of a suitable method of contraception for the duration of the study will not be required. 4. Subjects must have a best-corrected visual acuity (BCVA) of at least +1.0 log of the minimum angle of resolution (logMAR) (Snellen equivalent of 20/200) in the non-study eye (fellow eye). 5. Subjects must have an intraocular pressure (IOP) of \>8 mmHg and ≤22 mmHg in the study eye. 6. Subjects who are on Restasis, Xiidra or other cyclosporine ophthalmic eye drops must be on a stable dose for at least 4 months prior to Screening Visit 1 (Day -14 to Day 0) and remain compliant with the use of these medications throughout the duration of this study. 7. Subjects who are on artificial tears, oral antihistamines, beta blockers and diuretics must be on a stable dose for at least 1 month prior to Screening Visit 1 (Day -14 to Day 0) and remain compliant with the use of these medications throughout the duration of this study. 8. Subjects must be willing and able to attend all study visits and follow all instructions. 9. Subjects must be able to self-instill the study drug (if unable, a caregiver must be available to instill all doses of the study drug). 10. Have a history of use or desire to use an eye drop for dry eye symptoms for longer than the past 6 months.
Exclusion criteria
1. Females who are pregnant or nursing or planning to become pregnant during the study. Females of childbearing potential (not surgically sterilized or postmenopausal) may not participate in the study if they do not agree to use adequate birth control methods for the duration of the study. 2. Use of contact lenses in either eye during the study. Contact lens wear must have been discontinued at least 2 weeks prior to Baseline/Randomization Visit 2 (Day 1). 3. Use of corticosteroids or nonsteroidal anti-inflammatory agents (NSAID) (except oral doses of aspirin at 81 mg/day or lower) within 2 weeks of the initiation of study drug at Baseline/Randomization Visit 2 (Day 1) and for the remainder of the study. 4. Inhaled, ingested, sublingual, transdermal or topical products containing marijuana, tetrahydrocannabinol (THC) or cannabidiol (CBD) within 7 days of the first dose of study drug at Baseline/Randomization Visit 2 (Day 1) and for the remainder of the study. 5. Presence or history of treatment with systemic immunosuppressive or chemotherapeutic agents. 6. History of high IOP response to steroids. 7. Participated in an ophthalmic investigational product clinical trial within 30 days of Screening Visit 1 (Day -14 to Day 0). 8. Active collagen vascular disorder or autoimmune disease. 9. A condition or a situation, which in the investigator's opinion may put the subject at increased risk, confound study data, or interfere significantly with the subject's study participation. 10. Known hypersensitivity to any component of the study drug or procedural medications. 11. Known hypersensitivity to steroids. 12. Any active corneal epithelial/stromal pathology noted in the study eye at Screening Visit 1 (Day -14 to Day 0). 13. Any history of corneal surgery in the study eye (including corneal crosslinking, radial keratotomy, corneal transplant, or LASIK). 14. Any ocular surgery in the study eye within the past year. 15. Subject has punctal occlusion with any modality or a change in punctal plug status in either eye within the 3 months prior to Screening Visit 1 (Day -14 to Day 0). 16. Subject has a history of glaucoma. 17. Subject has a history of herpes simplex infection in either eye. 18. Subject has active corneal, conjunctival or canalicular pathology (including ocular infection \[bacterial, viral or fungal\]) in either eye. Specifically, active viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and mycobacterial infection of either eye and fungal diseases of the ocular structures (such as fungal keratitis). 19. Subject has thinning of the cornea or sclera in the study eye. 20. Subject has active anterior blepharitis in the study eye. 21. Subject has a history of uveitis in the study eye. 22. Subject is suffering from alcohol and/or drug abuse. 23. Subject has tested positive for the COVID-19 virus within 30 days prior to Screening Visit 1 (Day -14 to Day 0). 24. Subject has previously received treatment in this study protocol. 25. Subject is taking a medication, that in the opinion of the investigator, might interfere with the study parameters.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | Baseline and Day 8 | 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 minimum reduction of ≥1 point in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | Baseline and Day 15 | 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 minimum reduction of ≥1 point in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group. |
| Conjunctival Hyperemia Responder Analysis | Baseline and Day 8 | Conjunctival hyperemia was graded by Investigator using the scale below and clinical grade reference photos: Grade 0 (none: no hyperemia of the bulbar conjunctiva) Grade 0.5 (Grade 0 plus dilation of at least a couple of conjunctival blood vessels \[CBVs\] but less than Grade 1) Grade 1 (mild: the dilation of a few CBVs) Grade 1.5 (Grade 1 plus dilation of some CBVs but less than Grade 2) Grade 2 (moderate: the dilation of several CBVs) Grade 2.5 (Grade 2 plus dilation of many CBVs but less than Grade 3) Grade 3 (severe: the abundant and overwhelming dilation of many CBVs) Participants with a minimum reduction of ≥0.5 point in conjunctival hyperemia grade in the study eye from baseline were defined as responders, and response rates were summarized by treatment group. |
Countries
United States
Participant flow
Recruitment details
Study periods: Dosing Days 1-14. Follow-up (FU) to Day 28: Responders continued in the study; non-responders discontinued. Responders had to have a reduction of ≥1 unit in UNC DEMS score and a ≥0.5 point reduction in conjunctival hyperemia grade (study eye) compared to baseline. FU to Day 70 or rebound: Responders were followed up to Day 70 or rebound. Rebound was defined as worsening in UNC DEMS score of ≥1 unit and a worsening in conjunctival hyperemia of ≥0.5 point (study eye).
Pre-assignment details
Prior to each participant's assignment by chance to one of the three 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-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) Eye drops: 0.02% Betamethasone Sodium Phosphate (topical corticosteroid solution)
Dosing: One drop twice daily in the study eye for 14 days. | 47 |
| SURF-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) Eye drops: 0.02% Betamethasone Sodium Phosphate (topical corticosteroid solution)
Dosing: One drop twice daily in the study eye for 14 days. | 47 |
| SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) Eye drops: 0.04% Betamethasone Sodium Phosphate (topical corticosteroid solution)
Dosing: One drop twice daily in the study eye for 14 days. | 45 |
| SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) Eye drops: 0.04% Betamethasone Sodium Phosphate (topical corticosteroid solution)
Dosing: One drop twice daily in the study eye for 14 days. | 45 |
| Vehicle Eye drops: Placebo (topical vehicle solution)
Dosing: One drop twice daily in the study eye for 14 days. | 47 |
| Vehicle Eye drops: Placebo (topical vehicle solution)
Dosing: One drop twice daily in the study eye for 14 days. | 47 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Two-week Dosing Period (Days 1 - 14) | Did not complete dosing with study drug but remained in the study for safety follow-up at Day 28. | 1 | 0 | 0 |
| Two-week Dosing Period (Days 1 - 14) | Did not dose with study drug; missed Day 8 visit and did not return dosing diary. Lost to follow-up. | 0 | 0 | 1 |
| Two-week Dosing Period (Days 1 - 14) | Protocol Violation | 1 | 0 | 0 |
| Two-week Dosing Period (Days 1 - 14) | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | SURF-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) | SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) | Vehicle | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 years STANDARD_DEVIATION 15.9 | 60.9 years STANDARD_DEVIATION 14.1 | 59.7 years STANDARD_DEVIATION 15.3 | 60.2 years STANDARD_DEVIATION 15.03 |
| Conjunctival hyperemia score in study eye at baseline | 2.2 units on a scale STANDARD_DEVIATION 0.4 | 2.3 units on a scale STANDARD_DEVIATION 0.4 | 2.4 units on a scale STANDARD_DEVIATION 0.4 | 2.3 units on a scale STANDARD_DEVIATION 0.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 14 Participants | 13 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 30 Participants | 32 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 4 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 41 Participants | 40 Participants | 39 Participants | 120 Participants |
| Sex: Female, Male Female | 35 Participants | 34 Participants | 37 Participants | 106 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 10 Participants | 33 Participants |
| University of North Carolina Dry Eye Management Scale (UNC DEMS) Score at Baseline | 6.9 UNC DEMS units STANDARD_DEVIATION 1.2 | 7.2 UNC DEMS units STANDARD_DEVIATION 1.1 | 6.9 UNC DEMS units STANDARD_DEVIATION 1.2 | 7.0 UNC DEMS units STANDARD_DEVIATION 1.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 45 | 0 / 46 |
| other Total, other adverse events | 0 / 47 | 0 / 45 | 0 / 46 |
| serious Total, serious adverse events | 0 / 47 | 0 / 45 | 0 / 46 |
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 minimum reduction of ≥1 point in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group.
Time frame: Baseline and Day 8
Population: Intent-to-Treat (ITT) Population: included all randomized subjects regardless of whether post-baseline measures were collected, or study drug was received. For the ITT responder analysis, the analysis was conducted based on the observed available data without any imputation for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SURF-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 53.2 percentage of responders |
| SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 60.0 percentage of responders |
| Vehicle | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 65.2 percentage of responders |
Comparison: Exploratory Phase 2 Study; approximately 120 subjects (approximately 40 subjects per each of the 3 treatment groups) were planned to be enrolled in the study. The sample size was based on medical judgment. No formal sample size calculation was performed, and the sample size was empirical. However, the sample size selected was considered sufficient to adequately characterize the general safety and efficacy profile of the study treatments.p-value: 0.2933Fisher Exact
Secondary
Conjunctival Hyperemia Responder Analysis
Conjunctival hyperemia was graded by Investigator using the scale below and clinical grade reference photos: Grade 0 (none: no hyperemia of the bulbar conjunctiva) Grade 0.5 (Grade 0 plus dilation of at least a couple of conjunctival blood vessels \[CBVs\] but less than Grade 1) Grade 1 (mild: the dilation of a few CBVs) Grade 1.5 (Grade 1 plus dilation of some CBVs but less than Grade 2) Grade 2 (moderate: the dilation of several CBVs) Grade 2.5 (Grade 2 plus dilation of many CBVs but less than Grade 3) Grade 3 (severe: the abundant and overwhelming dilation of many CBVs) Participants with a minimum reduction of ≥0.5 point in conjunctival hyperemia grade in the study eye from baseline were defined as responders, and response rates were summarized by treatment group.
Time frame: Baseline and Day 8
Population: Intent-to-Treat (ITT) Population: included all randomized subjects regardless of whether post-baseline measures were collected, or study drug was received. For the ITT responder analysis, the analysis was conducted based on the observed available data without any imputation for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SURF-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) | Conjunctival Hyperemia Responder Analysis | 38.3 percentage of responders |
| SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) | Conjunctival Hyperemia Responder Analysis | 62.2 percentage of responders |
| Vehicle | Conjunctival Hyperemia Responder Analysis | 37.0 percentage of responders |
Comparison: Exploratory Phase 2 Study; approximately 120 subjects (approximately 40 subjects per each of the 3 treatment groups) were planned to be enrolled in the study. The sample size was based on medical judgment. No formal sample size calculation was performed, and the sample size was empirical. However, the sample size selected was considered sufficient to adequately characterize the general safety and efficacy profile of the study treatments.p-value: 0.0213Fisher Exact
Secondary
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 minimum reduction of ≥1 point in UNC DEMS score from baseline were defined as responders, and response rates were summarized by treatment group.
Time frame: Baseline and Day 15
Population: Intent-to-Treat (ITT) Population: included all randomized subjects regardless of whether post-baseline measures were collected, or study drug was received. For the ITT responder analysis, the analysis was conducted based on the observed available data without any imputation for missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SURF-200 (0.02% Betamethasone Sodium Phosphate in Vehicle) | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 88.9 percentage of responders |
| SURF-200 (0.04% Betamethasone Sodium Phosphate in Vehicle) | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 93.2 percentage of responders |
| Vehicle | University of North Carolina Dry Eye Management Scale (UNC DEMS) Responder Analysis | 82.2 percentage of responders |
Comparison: Exploratory Phase 2 Study; approximately 120 subjects (approximately 40 subjects per each of the 3 treatment groups) were planned to be enrolled in the study. The sample size was based on medical judgment. No formal sample size calculation was performed, and the sample size was empirical. However, the sample size selected was considered sufficient to adequately characterize the general safety and efficacy profile of the study treatments.p-value: 0.1966Fisher Exact