Efficacy and Safety of USL for Dry Eye Disease

Efficacy and Safety of USL for Dry Eye Disease (DED): a Randomized, Double-blind, Placebo-controlled, Parallel, Phase 2 Clinical Trial

The objective is to compare the USL and placebo in terms of efficacy and safety, and to determine the appropriate dosage.

Study Overview

• Status: Not yet recruiting
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: USL; Drug: USL Placebo

Detailed Description

This study is a phase 2, dose-finding, double-blind, randomized placebo-controlled trial of two different doses of USL compared with placebo. A total of 120 patients, aged over 19 years, with Corneal staining score(Oxford grading) ≥ 2 or TBUT < 10 sec and OSDI ≥ 10 points will be recruited at Daejeon University Daejeon Korean Medicine Hospital. Patients will take medications two times daily for 12 weeks, with 5 visiting days(screening, week 0, week 6, week 12, week 14).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yee Ran Lyu, PhD; Phone Number: 82-10-9904-8049; Email: onedoctor2ran@kiom.re.kr
• Study Contact Backup: Name: Chan-Sik Kim, PhD; Phone Number: 82-10-3018-0213; Email: chskim@kiom.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged over 19
• Screening both eyes, the corrected visual acuity is 0.2 or more
• Subjects with Fluorescein Corneal Staining score (Oxford grading) ≥ 2 or TBUT test ≤10 at screening
• Subjects with OSDI ≥ 13
• Subjects who voluntarily agreed to participate in this clinical study in written form

Exclusion Criteria:

• Current or history of ocular disorders possibly affecting the study results (ocular surgery, trauma, diseases) as followings within 2 months:

  1. Abnormal eyelid function: disorders of the eyelids or eyelashes
  2. Ocular allergies or currently under the treatment of allergic diseases of the eye (topical ocular mast cell stabilizer, antihistamine use, etc.)
  3. Cicatricial keratoconjunctivitis caused by herpetic keratopathy, conjunctival scarring (alkali damage, Steven-Johnson syndrome, cicatricial pemphigoid), pterygium, pinguecula, lack of congenital lacrimal, neurogenic keratitis, keratoconus, corneal transplantation
• Those with acute eye inflammation/infection within 1 month
• Those who have undergone eye surgery (including LASIK/LASIK) within 3 months
• Those who had taken lacrimal punctal occlusion, cauterization of the punctum, or intense pulsed light procedure within 3 months
• Those who wear contact lenses within 72 hours of screening or plan to wear contact lens during the study period
• Intraocular pressure (IOP)> 25 mmHg in more than one side
• Autoimmune disease (e.g., Sjogren's syndrome, Rheumatoid arthritis, systemic lupus erythematosus, Graves' disease)
• Those who have used cyclosporine or diquafosol use in any form (systemic, topical) within 1 month
• Medical condition or history within 1 month to be treated with topical agents besides artificial tears (glaucoma, ocular allergy, ocular inflammation/infectious disease, etc.)
• Those who have taken or are taking steroid drugs or immunosuppressants (Azathioprine, Tacrolimus, Cyclosporin, Mycophenolate mofetil etc.) that may affect immune function within 3 months prior to screening
• Those who had taken antihypertensive drugs such as antihistamine and beta blockers, diuretics, antidepressants (especially tricyclic antidepressants, Parkinson's treatment drugs, etc.) that can worsen dry eye cannot participate in this study
• Severe abnormal liver function tests (Alanine transaminase (ALT) or Aspartate transaminase (AST) values ≥ 2 times the upper limit of normal) and abnormal renal function (Creatinine values ≥ 2 times the upper limit of normal)
• Genetic disorders, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Comorbidities that may interrupt the treatment of cancers or clinically significant disorders of the kidney, liver, psychiatric system, cardiovascular system, respiratory system, endocrine system, and central nervous system, the safety assessment, or completion of this clinical study
• Unregulated hypertension (high blood pressure of 160 mmHg in the condenser or high blood pressure exceeding 100 mmHg in the relaxation period)
• Unregulated diabetes (fasting blood sugar (FBS) exceeding 180 mg/dL)
• Hepatitis A (active) or hepatitis B (active) or hepatitis C
• History of hypersensitivity reaction to active ingredients or excipients of the investigational product
• History of excessive alcohol use or drug addiction
• Pregnant or lactating women
• Those who did not agree to use contraception by medically permitted methods (e.g., surgical treatment of infertility, intrauterine device, condom or diaphragm, and injectable or insertable contraceptives) during the period from dosing of the investigational product to 90 days after the clinical study, among female subjects of childbearing potential and male subjects with the female partner
• Those who had experience of participating in a different clinical study within 4 weeks prior to participation in this clinical study
• Subjects who were determined to be ineligible to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard-dose USL group; 2 tablets(1 USL, 1 placebo) b.i.d for 12 weeks	Drug: USL; 500mg of Achyranthis Radix Extract; Drug: USL Placebo; USL Placebo
Experimental: High-dose USL group; 2 tablets(2 USL) b.i.d for 12 weeks	Drug: USL; 500mg of Achyranthis Radix Extract
Placebo Comparator: Placebo group; 2 tablets(2 placebo) b.i.d for 12 weeks	Drug: USL Placebo; USL Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TBUT(Tear break-up time)	The tear break-up time test measures the time in seconds. The time is from the last blinking to the point of tear layer defect or streak-like defect after blinking the eye with 1% of fluorescein. 10 seconds or more as normal, between 5 and 10 seconds as mild dry eye syndrome, and 5 seconds or less as severe dry eye syndrome.	Screening, 6 week, 12 week, 14 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OSDI(Ocular Surface Disease Index)	The Ocular Surface Disease Index consisted of 12 questions each of which included visual symptoms, visual work status, and environmental factors. The Ocular Surface Disease Index scores are ranged from 0 to 100, and the high score is the more severe the symptoms. The Ocular Surface Disease Index score is calculated as follows. : (Sum of all items answered × 25) / total number of questions answered	Screening, 6 week, 12 week, 14 week
VAS(Visual analog scale)	The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.	0 week, 6 week, 12 week, 14 week
Schirmer's test	The eyes were wiped and the Schirmer test paper was inserted into the right eye at 1/3 of the lower eyelid without eye anesthesia and inserted into the left eye. After 5 minutes with the eyes closed, the Schirmer test paper was removed from the right side in the order of insertion and the left side removed. The wet length was measured in millimeters and the length of the midpoint was measured when the wet border was oblique.	0 week, 6 week, 12 week, 14 week
Meibomian gland test	By expression of eyelid, scoring of expressibility and quality of meibum will be tested. Form of secretion predominantly secreted by the eight meibomian glands in the center of the lid was evaluated as follows. grade 0, clear meibum is easily expressed; grade 1, cloudy meibum is expressed with mild pressure; grade 2, cloudy meibum is expressed with more than moderate pressure; and grade 3, meibum cannot be expressed even with the hard pressure. Higher score means a worst outcome.	0 week, 6 week, 12 week, 14 week
Fluorescein corneal staining score - Oxford grading	The degree of corneal inflammation is scored (total of 5 points) according to the Oxford grading scale from 0 (no staining, A) to 5 (severe, confluent staining, >E).	Screening, 6 week, 12 week, 14 week
SPEED-II (Standard Patient Evaluation for Eye Dryness-II)	The SPEED questionnaire was designed in order to quickly track the progression of dry eye symptoms over time. This questionnaire gives a score from 0 to 28 that is the result of 8 items that assess frequency and severity of symptoms. The symptoms assessed include dryness, grittiness, scratchiness, irritation, burning, watering, soreness, and eye fatigue. The questionnaire further assesses whether these symptoms were not problematic, tolerable, uncomfortable, bothersome, or intolerable.	0 week, 6 week, 12 week, 14 week
Biomarkers	The levels of IL-1β, IFN-γ, TNF-α	0 week, 12 week

Collaborators and Investigators

• Sponsor: Chan-Sik Kim
• Investigators: Principal Investigator: Chan-Sik Kim, PhD, Korea Institute of Oriental Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: KIOM_2301_DED_USL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No