A Study to Assess the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution in Participants With Dry Eye

Study Overview
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Brief Summary
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The objective of this study was to compare the safety and efficacy of tanfanercept ophthalmic solution 0.25% with placebo for the treatment of the signs and symptoms of dry eye.

Official Title
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A Phase 3, Multicenter, Randomized, Double Masked and Placebo-Controlled Study Evaluating the Efficacy and Safety of Tanfanercept (HL036) Ophthalmic Solution 0.25% Compared to Placebo in Subjects With Dry Eye

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: 0.25% Tanfanercept Ophthalmic Solution
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a participant-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 minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1 Report a score of ≥ 2 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 a Schirmer's Test score of ≤ 10 millimeter (mm) and ≥ 1 mm in at least one eye at Visits 1 and 2 Have a corneal fluorescein staining score ≥ 2 according to the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining in at least 1 of the corneal regions (inferior, superior, or central) in at least 1 eye at Visits 1 and 2 Have a conjunctival redness score ≥ 1 according to the Ora Calibra® conjunctival redness for dry eye scale in at least 1 eye at Visits 1 and 2 Exclusion Criteria: 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 any cyclosporine-containing drops (such as Restasis®, Cequa®), or lifitegrast ophthalmic solution (Xiidra®) within 60 days of Visit 1 Have any previous experience using TNF inhibitor ophthalmic solutions, such Tanfanercept Ophthalmic Solution Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter (OTC) 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) Be a woman who is pregnant, nursing or planning a pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Placebo Run-in<br>Participants self-administered placebo ocular drops, twice daily (BID) in both eyes for 14 days in the Placebo Run-in Period. | Drug: Placebo<br>* Placebo vehicle solution.<br>|
| Experimental: 0.25% Tanfanercept Ophthalmic Solution<br>Participants self-administered tanfanercept 0.25 percent (%) ophthalmic solution as topical ophthalmic drops, BID for up to 8 weeks in Treatment Period. | Drug: 0.25% Tanfanercept Ophthalmic Solution<br>* Tanfanercept ophthalmic solution.<br>* Other names: HL036;|
| Placebo Comparator: Placebo<br>Participants self-administered tanfanercept placebo (vehicle solution) solution as topical ophthalmic drops, BID for up to 8 weeks in Treatment Period. | Drug: Placebo<br>* Placebo vehicle solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Central Corneal Staining Score (CCSS) at Day 57 | CCSS was graded using the Ora Calibra® Corneal and Conjunctival Fluorescein Staining Scale. The Ora Calibra® Corneal and Conjunctival Staining Scale ranged 0 = None, 1 = Trace, 2 = Mild, 3 = Moderate, and 4 = Severe; lower score indicated improvement. | Baseline, Day 57 (Week 8) | 
| Change From Baseline in Eye Dryness Score (EDS) Assessed by Visual Analogue Scale at Day 57 | Eye dryness score was scored on a Visual Analogue Scale (VAS) that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline, Day 57 (Week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Central Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Superior Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Inferior Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Temporal Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Nasal Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Corneal Sum | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. Fluorescein total staining score for corneal regions was derived as the sum of the reported scores for the inferior, superior, and central regions. Total score ranged between 0 to 12, and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Conjunctival Sum | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. Fluorescein total staining score for conjunctival regions was derived the sum of the reported scores for the nasal and temporal regions. Total score ranged between 0 to 8, and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Fluorescein Staining at Weeks 1, 2, 4, and 8: Total Staining | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of fluorescein staining. The score ranged from 0 to 4 (0=none and 4=severe), and lower score indicated improvement. Fluorescein total staining score for corneal and conjunctival regions was derived as the sum of the reported scores for the inferior, superior, central, temporal, and nasal regions. Total score ranged between 0 to 20, and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Central Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Superior Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Inferior Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Temporal Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Nasal Region | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Corneal Sum | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Lissamine Green total staining score for corneal regions was derived as the sum of the reported scores for the inferior, superior, and central regions. Total score ranged between 0 to 12,and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Conjunctival Sum | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Lissamine Green total staining score for conjunctival regions was derived as the sum of the reported scores for the nasal and temporal regions. Total score ranged between 0 to 8, and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Lissamine Green Staining at Weeks 1, 2, 4, and 8 : Total Staining | The score for individual region was assessed by the Ora Calibra® corneal and conjunctival staining scale for grading of lissamine green staining. The score ranges from 0 to 4 (0=none and 4=severe), and lower score indicates improvement. Lissamine Green total staining score for corneal and conjunctival regions was derived as the sum of the reported scores for the inferior, superior, central, nasal, and temporal regions. Total score ranged between 0 to 20, and lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Conjunctival Redness Score at Weeks 1, 2, 4, and 8 | It was evaluated by the Ora Calibra® conjunctival redness scale for dry eye. The score ranged from 0 to 4 (0=none and 4=severe), where lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Schirmer's Test Score at Weeks 2, 4, and 8 | The Schirmer test strip was placed in the lower temporal lid margin of each eye. Participants were instructed to close their eyes and after 5 minutes had elapsed, the length of moistened area of schirmer strip was recorded (millimeter [mm]) for each eye. | Baseline; Weeks 2, 4, and 8 | 
| Change From Baseline in Tear Film Break-up Time at Weeks 1, 2, 4, and 8 | Sodium fluorescein solution was instilled into each eye and participants were instructed to blinked several times. The time it took to form micelles from the time that the eye is opened was noted. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Burning/Stinging | Participants rated ocular symptom of burning/stinging by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Foreign Body Sensation | Participants rated ocular symptom of foreign body sensation by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Itching | Participants rated ocular symptom of itching by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Blurred Vision | Participants rated ocular symptom of blurred vision by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Eye Dryness | Participants rated ocular symptom of eye dryness by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Photophobia | Participants rated ocular symptom of photophobia by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Visual Analogue Scale at Weeks 1, 2, 4, and 8 : Pain | Participants rated ocular symptom of pain by placing a vertical mark on VAS that ranged from 0%-100% (0=no discomfort; 100=maximal discomfort). | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ocular Surface Disease Index (OSDI) at Weeks 1, 2, 4, and 8 | OSDI was a simple 12-question survey that rated the severity of the participant's dry eye disease based on the symptoms. Each question response ranged from 0 to 4, where 0 = None of the Time, 1 = Some of the Time, 2 = Half of the Time, 3 = Most of the Time, and 4 = All of the Time. Total OSDI score = (Sum of all answered questions) * 25/ (number of questions answered); which ranged from 0 to 100, with higher score representing greater disability. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ora Calibra® Ocular Discomfort Scale at Weeks 1, 2, 4, and 8 | It was assessed by the Ora Calibra® ocular discomfort scale. The score ranged from 0 to 4 (0=none and 4=severe), where lower score indicated improvement. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire at Weeks 1, 2, 4, and 8 : Burning Discomfort | Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye included rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of burning at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire at Weeks 1, 2, 4, and 8 : Dryness Discomfort | Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye included rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of dryness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire at Weeks 1, 2, 4, and 8 : Grittiness Discomfort | Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye included rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of grittiness at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. | Baseline; Weeks 1, 2, 4, and 8 | 
| Change From Baseline in Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire at Weeks 1, 2, 4, and 8 : Stinging Discomfort | Ora Calibra® ocular discomfort & 4-symptom questionnaire for dry eye included rating of the severity of 5 symptoms: ocular discomfort, burning, dryness, grittiness, and stinging. Participants rated the severity of stinging at all scheduled visits on 0 to 5 scale, where 0=none and 5=severe. Higher score represent higher severity. | Baseline; Weeks 1, 2, 4, and 8 | 
| Ora Calibra® Drop Comfort Assessment at Week 1 | Ora Calibra® drop comfort scale ranged from 0 to 10. A score of 0 indicated comfortable and 10 indicated uncomfortable. Lower score indicated better comfort level. Immediately Upon Instillation, 1 Minute Post Instillation and 2 Minutes Post Instillation at Week 1 | Week 1 |