Phase 2, Multi-center, Randomized, Double- Masked and Placebo-Controlled Study of YP-P10 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye (ICECAP 1)

Study Overview
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Brief Summary
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The objective of this study is to compare the safety and efficacy of YP-P10 Ophthalmic Solution to placebo for the treatment of the signs and symptoms of dry eye.

Detailed Description
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The clinical hypotheses for this study is that 0.3% YP-P10 Ophthalmic Solution twice daily (BID) and 1.0% YP-P10 Ophthalmic Solution BID are superior to YP-P10 Placebo Ophthalmic Solution (vehicle) for the primary endpoints of signs and symptoms of dry eye, as follows: Sign: Total corneal fluorescein staining score of the study eye using the modified NEI grading scale, measured by mean change from baseline (Visit 2, Pre- Controlled Adverse Environment [CAE®]) to Visit 6 Symptom: Ocular discomfort score of both eyes using the Visual Analog Scale (VAS) Ocular Discomfort Scale, measured by mean change from baseline (Visit 2, Pre-CAE®) to Visit 6

Official Title
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A Phase 2, Multi-center, Randomized, Double- Masked and Placebo-Controlled Study Evaluating the Efficacy and Safety of YP-P10 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye (ICECAP 1)

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: 0.3% YP-P10 Ophthalmic Solution
* Drug: 1% YP-P10 Ophthalmic Solution
* Drug: YP-P10 Placebo Ophthalmic Solution (vehicle)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Individuals eligible to participate in this study must meet all of the following criteria: 0. Be at least 18 years of age; Provide written informed consent; Be willing and able to comply with all study procedures; Have a patient-reported history of dry eye for at least 6 months prior to Visit 1; Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1; Have a best corrected visual acuity (BCVA) of 0.7 logarithm of the minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1; Have a score of ≥ 2 for both eyes according to the Ora Calibra® Ocular Discomfort & 4- Symptom Questionnaire in at least one of the dry eye symptoms at Visits 1 and 2; Have an unanesthetized Schirmer's Test score of ≤ 10 mm/5 minutes and ≥ 1 mm/5 minutes in at least one eye at Visits 1 and 2; Have a corneal fluorescein staining score of ≥ 2 according to the Ora Calibra® Corneal and Conjunctival Staining Scale for Grading of Fluorescein Staining in at least one region in one eye at Visits 1 and 2 and a central score ≥ 1 in the same eye; Have a conjunctival redness score ≥ 1 according to the Ora Calibra® Conjunctival Redness for Dry Eye Scale in at least one eye at Visits 1 and 2 pre-CAE®; Demonstrate in the same eye(s) a response to the CAE® at Visits 1 and 2 as defined by: Having at least a ≥1 point increase in fluorescein staining in the inferior region in at least one eye following CAE® exposure; a. Reporting an Ocular Discomfort score ≥ 3 at 2 or more consecutive time points in at least one eye during CAE® exposure (if a subject has an Ocular Discomfort rating of 3 at time = 0 for an eye, s/he must report an Ocular Discomfort rating of 4 for two consecutive measurements for that eye). Note: a subject cannot have an Ocular Discomfort score of 4 at time = 0); Have at least one eye, the same eye, satisfy all criteria for 8, 9, 10 and 11 above; A negative urine pregnancy test if female of childbearing potential (those who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or post-menopausal [12 months after last menses]) and must use adequate birth control through the study period. For non-sexually active females, abstinence may be regarded as an adequate method of birth control.) Exclusion Criteria: • Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study: 0. Have any clinically significant slit lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction, lid margin inflammation, or active ocular allergies that require therapeutic treatment, and/or in the opinion of the investigator may interfere with study parameters; Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1; Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study; Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months; Have used Restasis®, Xiidra®, or Cequa®, Eysuvis™ and Tyrvaya™ within 60 days of Visit 1; Have had any ocular and/or lid surgeries in the past 6 months or have any planned ocular and/or lid surgeries over the study period; Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1; Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study); the respective wash- out periods are required for the following medications: Antihistamines (including ocular): 72 hours prior to Visit 1 Oral aspirin or aspirin-containing products allowed if dose has been stable over past 30 days prior to Visit 1 and no change in dose is anticipated during the study period Corticosteroids or mast cell stabilizers (including ocular): 14 days prior to Visit 1 Any medication (oral or topical) known to cause ocular drying that has not been administered as a stable dose for at least 30 days prior to Visit 1 and during the study All other topical ophthalmic preparations (including artificial tear substitutes) other than the study drops: 72 hours prior to Visit 1 Have an uncontrolled systemic disease; Be a woman who is pregnant, nursing, or planning a pregnancy; Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 6 (or early termination visit) if of childbearing potential. Non- childbearing potential is defined as a woman who is permanently sterilized (e.g., has had a hysterectomy or tubal ligation), or is post- menopausal (without menses for 12 consecutive months); Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as a diaphragm or condom; intrauterine device; or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use adequate birth control as defined above for the remainder of the study; Have a known allergy and/or sensitivity to the test article or its components; Have a condition or be in a situation which the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study; Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1; Be unable or unwilling to follow instructions, including participation in all study assessments and visits.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: multicenter, randomized, double-masked, placebo-controlled clinical study. Subjects will be randomized to one of the following treatment arms at Visit 2 (Day 1): 0.3% YP-P10 Ophthalmic Solution: 1 drop BID in each eye (N =  80) 1% YP-P10 Ophthalmic Solution: 1 drop BID in each eye (N =  80) YP-P10 Placebo Ophthalmic Solution (vehicle): 1 drop BID in each eye (N =  80)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.3% YP-P10 Ophthalmic Solution<br> | Drug: 0.3% YP-P10 Ophthalmic Solution<br>* Drug: YP-P10 Ophthalmic Solution<br>|
| Active Comparator: 1% YP-P10 Ophthalmic Solution<br> | Drug: 1% YP-P10 Ophthalmic Solution<br>* Drug: YP-P10 Ophthalmic Solution<br>|
| Placebo Comparator: YP-P10 Placebo Ophthalmic Solution (vehicle)<br> | Drug: YP-P10 Placebo Ophthalmic Solution (vehicle)<br>* Placebo YP-P10 Placebo Ophthalmic Solution (vehicle)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total corneal fluorescein staining score of the study eye using the modified NEI scale | Sign | Day 85 | 
| Ocular discomfort score of both eyes using the VAS | Symptom | Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorescein staining | by region and total staining of each eye | Up to 13 weeks | 
| Lissamine green staining on the modified NEI scale | by region and total staining of each eye | Up to 13 weeks | 
| Conjunctival redness | of each eye | Up to 13 weeks | 
| Schirmer's Test | of each eye | Up to 13 weeks | 
| Tear film break-up time (TFBUT) | of each eye | Up to 13 weeks | 
| Ocular Surface Disease Index© (OSDI©) | of eye | Up to 13 weeks | 
| Dryness as measured by visual analog scale (VAS) | Burning/stinging, Itching, Foreign body sensation, Blurred vision, Photophobia, Pain, Eye | Up to 13 weeks | 
| Daily compliance diary | Verification of compliance | Up to 13 weeks | 
| Drop comfort | A drop comfort evaluation will be performed immediately upon administration of study drug and then at 1, 2, and 3 minutes following initial dosing using the Ora Calibra Drop Comfort Scale | Up to 13 weeks | 
| Visual acuity | assessed using an ETDRS chart | Up to 13 weeks | 
| Slit-lamp evaluation Biomicroscopy | Slit lamp biomicroscopic observations will be graded as Normal or Abnormal | Up to 13 weeks | 
| Adverse event query | Each subject will be queried regarding adverse events | Up to 13 weeks | 
| Intraocular Pressure (IOP) by contact tonometry by the examiner | A single measurement is made | Up to 13 weeks | 
| Dilated fundoscopy | using indirect ophthalmoscopy. The Investigator will make observations of the vitreous, retina, macula, choroid and optic nerve. | Up to 13 weeks |