Clinical trial NCT05467293: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dry Eye
Lead sponsor: Yuyu Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-20
Enrollment: 257
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

• Individuals eligible to participate in this study must meet all of the following criteria: 0. Be at least 18 years of age;

1. Provide written informed consent;
2. Be willing and able to comply with all study procedures;
3. Have a patient-reported history of dry eye for at least 6 months prior to Visit 1;
4. Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
5. 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;
6. 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;
7. 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;
8. 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;
9. 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®;
10. 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);
11. Have at least one eye, the same eye, satisfy all criteria for 8, 9, 10 and 11 above;
12. 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;

1. Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1;
2. Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study;
3. Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months;
4. Have used Restasis®, Xiidra®, or Cequa®, Eysuvis™ and Tyrvaya™ within 60 days of Visit 1;
5. 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;
6. Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;
7. 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
8. Have an uncontrolled systemic disease;
9. Be a woman who is pregnant, nursing, or planning a pregnancy;
10. 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);
11. 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;
12. Have a known allergy and/or sensitivity to the test article or its components;
13. 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;
14. Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days of Visit 1;
15. Be unable or unwilling to follow instructions, including participation in all study assessments and visits.

Primary outcomes:
measure: Total Corneal Fluorescein Staining
timeFrame: Day 85
measure: Ocular Discomfort Score
timeFrame: Day 85
Secondary outcomes:
measure: Fluorescein Staining: Inferior
timeFrame: 13 weeks
measure: Fluorescein Staining: Superior
timeFrame: 13 weeks
measure: Fluorescein Staining: Central
timeFrame: 13 weeks
measure: Fluorescein Staining: Temporal
timeFrame: 13 weeks
measure: Fluorescein Staining: Nasal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Conjunctival Sum
timeFrame: 13 weeks
measure: Lissamine Green Staining: Inferior Temporal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Superior Temporal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Temporal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Inferior Nasal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Superior Nasal
timeFrame: 13 weeks
measure: Lissamine Green Staining: Nasal
timeFrame: 13 weeks
measure: Conjunctival Redness
timeFrame: 13 weeks
measure: Unanesthetized Schirmer's Test
timeFrame: 13 weeks
measure: Tear Film Break-up Time (TFBUT)
timeFrame: 13 weeks
measure: Ocular Surface Disease Index (OSDI): Subtotal 1-5
timeFrame: 13 weeks
measure: Ocular Surface Disease Index (OSDI): Subtotal 6-9
timeFrame: 13 weeks
measure: Ocular Surface Disease Index (OSDI): Subtotal 10-12
timeFrame: 13 weeks
measure: Ocular Surface Disease Index (OSDI): Total
timeFrame: 13 weeks
measure: Burning/Stinging
timeFrame: 13 weeks
measure: Itching
timeFrame: 13 weeks
measure: Foreign Body Sensation
timeFrame: 13 Weeks
measure: Blurred Vision
timeFrame: 13 Weeks
measure: Eye Dryness
timeFrame: 13 Weeks
measure: Photophobia
timeFrame: 13 Weeks
measure: Pain in Eyes
timeFrame: 13 Weeks
measure: Treatment Compliance Using a Daily Compliance Diary
timeFrame: 13 weeks
measure: Drop Comfort - Positive Response
timeFrame: 13 weeks
measure: Visual Acuity - Subjects With Increase Greater Than 0.2 logMAR
timeFrame: 13 weeks
measure: Slit-lamp Evaluation Biomicroscopy - Subjects That Had a Shift From Normal/Abnormal NCS to Abnormal CS
timeFrame: 13 weeks
measure: Adverse Event Query - TEAEs
timeFrame: 13 weeks
measure: Adverse Event Query - Ocular TEAEs
timeFrame: 13 Weeks
measure: Adverse Event Query - Non Ocular TEAEs
timeFrame: 13 Weeks
measure: Adverse Event Query - TEAEs Causing Premature Treatment Discontinuation
timeFrame: 13 Weeks
measure: Adverse Event Query - TEAEs Suspected to be Related to Study Drug
timeFrame: 13 Weeks
measure: Adverse Event Query - SEA Reported
timeFrame: 13 Weeks
measure: Dilated Fundoscopy: Shift From Normal/Abnormal NCS to Abnormal CS
timeFrame: 13 weeks
measure: Intraocular Pressure (IOP) by Contact Tonometry by the Examiner: Unsafe and Abnormal Ranges
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cornea Consultants of Arizona
state: Arizona
city: Newport Beach
country: United States
facility: Aesthetic Eye Care Institute
state: California
city: Colorado Springs
country: United States
facility: Vision Institute
state: Colorado
city: Andover
country: United States
facility: Andover Eye Associates
state: Massachusetts
city: Apex
country: United States
facility: NC Eye Associates
state: North Carolina
city: Garner
country: United States
facility: Oculus Research
state: North Carolina
city: Memphis
country: United States
facility: Total Eye Care
state: Tennessee
Study officials:
References: