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)

Phase 2

Completed

Conditions: Dry Eye

Interventions: Drug: 0.3% YP-P10 Ophthalmic Solution
Drug: 1% YP-P10 Ophthalmic Solution
Drug: YP-P10 Placebo Ophthalmic Solution (vehicle)

Registration Number: NCT05467293

Lead Sponsor: Yuyu Pharma, Inc.

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 257

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
  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
  2. Corticosteroids or mast cell stabilizers (including ocular): 14 days prior to Visit 1
  3. 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
  4. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
0.3% YP-P10 Ophthalmic Solution	0.3% YP-P10 Ophthalmic Solution	-
1% YP-P10 Ophthalmic Solution	1% YP-P10 Ophthalmic Solution	-
YP-P10 Placebo Ophthalmic Solution (vehicle)	YP-P10 Placebo Ophthalmic Solution (vehicle)	-

Primary Outcome Measures

Name	Time	Method
Total Corneal Fluorescein Staining	Day 85	Modified National Eye Institute Scale; 0-20: Higher is Worse
Ocular Discomfort Score	Day 85	Visual Analogue Scale; 0-100: Higher is Worse

Secondary Outcome Measures

Name	Time	Method
Lissamine Green Staining: Temporal	13 weeks	Modified National Eye Institute Scale; 0-4 Higher is Worse
Lissamine Green Staining: Inferior Nasal	13 weeks	Modified National Eye Institute Scale; 0-4 Higher is Worse
Ocular Surface Disease Index (OSDI): Subtotal 1-5	13 weeks	Ocular Surface Disease Index Scale 0-100 (higher is worse)
Pain in Eyes	13 Weeks	Visual Analog Scale; 0-100: Higher is Worse
Fluorescein Staining: Nasal	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Conjunctival Redness	13 weeks	Ora Calibra Scale; 0-4 Higher is Worse
Ocular Surface Disease Index (OSDI): Subtotal 6-9	13 weeks	Ocular Surface Disease Index Scale 0-100 (higher is worse)
Ocular Surface Disease Index (OSDI): Subtotal 10-12	13 weeks	Ocular Surface Disease Index Scale 0-100 (higher is worse)
Ocular Surface Disease Index (OSDI): Total	13 weeks	Ocular Surface Disease Index Scale 0-100 (higher is worse)
Burning/Stinging	13 weeks	Visual Analog Scale; 0-100: Higher is Worse
Itching	13 weeks	Visual Analog Scale; 0-100: Higher is Worse
Foreign Body Sensation	13 Weeks	Visual Analog Scale; 0-100: Higher is Worse
Blurred Vision	13 Weeks	Visual Analog Scale; 0-100: Higher is Worse
Eye Dryness	13 Weeks	Visual Analog Scale; 0-100: Higher is Worse
Photophobia	13 Weeks	Visual Analog Scale; 0-100: Higher is Worse
Fluorescein Staining: Superior	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Fluorescein Staining: Central	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Fluorescein Staining: Inferior	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Fluorescein Staining: Temporal	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Lissamine Green Staining: Nasal	13 weeks	Modified National Eye Institute Scale; 0-4 Higher is Worse
Unanesthetized Schirmer's Test	13 weeks	score on a scale of ≤ 10 mm/5 minutes and ≥ 1 mm/5 minutes in at least one eye. Schirmer's test can be interpreted as follows: 0 to 5 mm: extremely dry eyes; 5 to 10 mm: moderately dry eyes; 10 to 15 mm: possible dry eyes; Longer than 15 mm: normal tear function.
Tear Film Break-up Time (TFBUT)	13 weeks
Lissamine Green Staining: Conjunctival Sum	13 weeks	Modified National Eye Institute Scale; 0-24: Higher is Worse
Lissamine Green Staining: Inferior Temporal	13 weeks	Modified National Eye Institute Scale; 0-4: Higher is Worse
Lissamine Green Staining: Superior Temporal	13 weeks	Modified National Eye Institute Scale; 0-4 Higher is Worse
Lissamine Green Staining: Superior Nasal	13 weeks	Modified National Eye Institute Scale; 0-4 Higher is Worse
Adverse Event Query - TEAEs	13 weeks	Each subject will be queried regarding adverse events
Adverse Event Query - Ocular TEAEs	13 Weeks	Each subject will be queried regarding adverse events
Treatment Compliance Using a Daily Compliance Diary	13 weeks	Self-Administrating with use of Daily Compliance Diary. Subject daily diaries were collected at Visits 1 through 6, and the subject's used and unused study drug ampules were collected at Visit 3 through 6. Dosing compliance was based on the used and unused ampule count. If the subject was less than 80% or more than 125% compliant with dosing based on the expected number of used ampules, then the subject was deemed noncompliant and a dosing deviation was recorded. Dosing compliance (% compliance) was assessed by calculating the number of actual doses received and comparing that to the number of expected doses as follows: Compliance (%) = Number of Actual Doses Received / Number of Expected Doses x 100% The number of expected doses that will be used for calculating compliance was calculated as: 2 x \[(Date of Last Dose - Date of First Dose) + 1\]
Drop Comfort - Positive Response	13 weeks	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
Visual Acuity - Subjects With Increase Greater Than 0.2 logMAR	13 weeks	Visual Acuity was assessed using an ETDRS chart
Slit-lamp Evaluation Biomicroscopy - Subjects That Had a Shift From Normal/Abnormal NCS to Abnormal CS	13 weeks	Slit lamp biomicroscopic observations will be graded as Normal or Abnormal
Adverse Event Query - Non Ocular TEAEs	13 Weeks	Each subject will be queried regarding adverse events
Adverse Event Query - TEAEs Causing Premature Treatment Discontinuation	13 Weeks	Each subject will be queried regarding adverse events
Adverse Event Query - TEAEs Suspected to be Related to Study Drug	13 Weeks	Each subject will be queried regarding adverse events
Adverse Event Query - SEA Reported	13 Weeks	Each subject will be queried regarding adverse events
Dilated Fundoscopy: Shift From Normal/Abnormal NCS to Abnormal CS	13 weeks	using indirect ophthalmoscopy. The Investigator will make observations of the vitreous, retina, macula, choroid and optic nerve.
Intraocular Pressure (IOP) by Contact Tonometry by the Examiner: Unsafe and Abnormal Ranges	13 weeks	A single measurement is made

Trial Locations

Locations (7): Cornea Consultants of Arizona
🇺🇸
Phoenix, Arizona, United States
Vision Institute
🇺🇸
Colorado Springs, Colorado, United States
Andover Eye Associates
🇺🇸
Andover, Massachusetts, United States
Aesthetic Eye Care Institute
🇺🇸
Newport Beach, California, United States
NC Eye Associates
🇺🇸
Apex, North Carolina, United States
Oculus Research
🇺🇸
Garner, North Carolina, United States
Total Eye Care
🇺🇸
Memphis, Tennessee, United States