Piiloset Trehalose Emulsion Eye Drop Study in Moderate or Severe Dry Eye

Study Overview
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Brief Summary
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The study evaluates the safety, ocular tolerability and efficacy of emulsion eye drops with sacha inchi seed oil, trehalose and hyaluronic acid in the treatment of moderate or severe dry eye in adult patients. The investigative device is studied in comparison with control eye drops containing hyaluronic acid for up to 30 days.

Detailed Description
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According to the current view on dry eye disease, tear film instability, tear film hyperosmolarity, and ocular surface inflammation and damage are identified as etiological factors. The first-line medicinal management options include ocular lubricants such as eye drops and sprays. Emulsion eye drops are a relatively recent entity among topical therapies with an intention to account for deficiencies in the outermost lipid layer of the tear film. Piiloset Trehalose Emulsion Eye Drops was developed to target and restore the three main layers (mucin, aqueous, and lipid) of the tear film and to counteract the key etiological factors leading to dry eye. Hyaluronic acid and the oil component are intended to restore tear film instability, the hypo-osmolar composition and trehalose as an osmoprotectant are intended to protect the ocular epithelium against hyperosmolarity, and ocular surface inflammation and cellular damage are prevented by the cytoprotective and/or anti-oxidative action of hyaluronic acid, trehalose, and sacha inchi oil components. Additional water binding in the tear film is provided by hyaluronic acid, trehalose, and glycerol. Lubricating the ocular surface by high-molecular-weight hyaluronic acid will extend the precorneal retention time. Adjustments made to certain physical and chemical parameters in the formulation are anticipated to improve tear film spreading and adhesion. The optically clear o/w emulsion formulation is free of preservatives, materials of animal origin, phosphates, or alcohol. The combined action of the individual components is expected to produce clinically relevant mitigation of the signs and symptoms of dry eye. The study comprises three Parts with scheduled visits on Day 1 (all Parts) and on end-of-study date (Parts 2 and 3) to the study centre. Each study subject will participate in no more than one Part of the study.

Official Title
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A Randomized, Active-controlled, Parallel, Double-blind Study on the Safety, Ocular Tolerability and Efficacy of Piiloset Trehalose Emulsion Eye Drop in Adult Patients With Moderate or Severe Dry Eye

Conditions
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Dry Eye Syndrome

Intervention / Treatment
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* Device: Piiloset Trehalose Emulsion Eye Drops
* Device: Control Eye Drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness to give informed written consent prior to any screening procedure after explanation of the nature and possible consequences of the study. Age between 18 and 80 years. At least two the following conditions (A and B): A. Symptomatic dry eye with OSDI score ≥20. AND B1. Tear film break-up time (TBUT) <10 seconds. OR B2. Positive ocular (corneal and conjunctival) staining pattern Body weight at least 45 kg. Under stable topical and/or systemic therapy for at least 4 weeks before the study procedures and apparent ability and willingness to abstain from other therapies until completion of the study period. Ability and willingness to self-administer eye drops. Ability and willingness to understand and fill in the OSDI questionnaire. Ability and willingness to comply with the study protocol and other study-related procedures. Exclusion Criteria: History of ocular surgery, trauma, or refractive laser vision correction procedure less than 3 months earlier. Evidence of acute or chronic infection in the cornea or conjunctiva. Diagnosis of Sjögren's syndrome. Unwillingness or apparent disability to discontinue contact lens use during study period and at least one week before the first dosing day. Current ocular allergy symptoms. Known allergy to any constituent of the trehalose emulsion eye drops or control eye drops. Currently pregnant, nursing or planning to become pregnant before completion of the study period. Any other condition that may, in the Investigator's opinion, jeopardize the safety or availability of the subject or adherence to the study protocol or may interfere with the interpretation of the results and would thus make the subject inappropriate for entry in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Part 1. Piiloset Trehalose Emulsion Eye Drop is administered on the worst eye four times during office hours of one day at the study centre. Part 2. Piiloset Trehalose Emulsion Eye Drop is self-administered on a randomized eye and the control eye drops on the contralateral eye three times a day for 10 days in a double-blinded fashion. Part 3. Either Piiloset Trehalose Emulsion Eye Drop or the control eye drops are self-administered on both eyes three times a day for 30 days in a randomized and double-blinded fashion.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emulsion Eye Drops<br>Daily treatment with Piiloset Trehalose Emulsion Eye Drops | Device: Piiloset Trehalose Emulsion Eye Drops<br>* Topical application of preservative-free multidose Piiloset Trehalose Emulsion Eye Drops 3 times daily<br>|
| Active Comparator: Control Eye Drops<br>Daily treatment with Hyaluronic Acid Eye Drops (a CE-marked medical device) | Device: Control Eye Drops<br>* Topical application of preservative-free multidose Hyaluronic Acid Eye Drops 3 times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline OSDI | Ocular Surface Disease Index (OSDI) is a questionnaire consisting of 12 questions subdivided into 3 subscales for measuring the frequency of dry eye symptoms, vision-related quality of life and environmental triggers during the previous week. Answers to each question are on a scale of 0 (None of the time) to 4 (All of the time). Both total OSDI and its subscale scores are on a scale of 0 to 100, calculated as follows: score = (sum of scores for questions answered/number of questions answered) x 25. Higher scores represent greater disability. | From baseline to Day 30 (Part 3) | 
| Change From Baseline Tear Osmolarity | Instrumental assay of tear fluid osmolarity (mOsm/L) | From baseline to Day 30 (Part 3) | 
| Change From Baseline TBUT | Tear film break-up time (TBUT) (s) | From baseline to Day 30 (Part 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Blink Rate | Measurement of spontaneous eyelid blinks per minute | From baseline to Day 30 (Part 3) | 
| Change From Baseline Ocular Protection Index (OPI) | OPI is the ratio of TBUT/IBI (IBI, interblink interval calculated from blink rate). An OPI value >1 indicates that TBUT (s) exceeds IBI (s) and that the ocular surface is mostly tear-film protected, because tear film break-ups do not take place within spontaneous blink cycles. | From baseline to Day 30 (Part 3) | 
| Change From Baseline Corneal Staining | Corneal staining score is assessed as the average number of punctate dots on an ordinal scale of 0, 1, 2, 3, 4, and 5 (Oxford scale) when compared to a pictorial standard. The number of dots increases on a log scale. Higher score represents more intense staining. | From baseline to Day 30 (Part 3) | 
| Change From Baseline Conjunctival (Temporal) Staining | Conjunctival staining score is assessed as the average number of punctate dots on an ordinal scale of 0, 1, 2, 3, 4, and 5 (Oxford scale) when compared to a pictorial standard. The number of dots increases on a log scale. Higher score represents more intense staining. | From baseline to Day 30 (Part 3) | 
| Change From Baseline Conjunctival (Nasal) Staining | Conjunctival staining score is assessed as the average number of punctate dots on an ordinal scale of 0, 1, 2, 3, 4, and 5 (Oxford scale) when compared to a pictorial standard. The number of dots increases on a log scale. Higher score represents more intense staining. | From baseline to Day 30 (Part 3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lubricant Eye Drops, Moderate or Severe Dry Eye, Hyaluronic Acid, Trehalose, Disaccharides, Polysaccharides, Fatty Acids, Omega-3, Tears, Osmolar Concentration, Anterior Eye Segment, Severity of Illness Index