Clinical trial NCT03569202: Piiloset Trehalose Emulsion Eye Drop Study in Moderate or Severe Dry Eye
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dry Eye Syndrome
Keywords: 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
Lead sponsor: Kuopio University Hospital
Sponsor class: OTHER
Collaborators: name: Finnsusp Ltd.
name: 4Pharma Ltd.
name: Business Finland
First posted: 2018-06-26
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Ability and willingness to give informed written consent prior to any screening procedure after explanation of the nature and possible consequences of the study.
2. Age between 18 and 80 years.
3. 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
4. Body weight at least 45 kg.
5. 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.
6. Ability and willingness to self-administer eye drops.
7. Ability and willingness to understand and fill in the OSDI questionnaire.
8. Ability and willingness to comply with the study protocol and other study-related procedures.

Exclusion Criteria:

1. History of ocular surgery, trauma, or refractive laser vision correction procedure less than 3 months earlier.
2. Evidence of acute or chronic infection in the cornea or conjunctiva.
3. Diagnosis of Sjögren's syndrome.
4. Unwillingness or apparent disability to discontinue contact lens use during study period and at least one week before the first dosing day.
5. Current ocular allergy symptoms.
6. Known allergy to any constituent of the trehalose emulsion eye drops or control eye drops.
7. Currently pregnant, nursing or planning to become pregnant before completion of the study period.
8. 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.

Primary outcomes:
measure: Change From Baseline OSDI
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Tear Osmolarity
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline TBUT
timeFrame: From baseline to Day 30 (Part 3)
Secondary outcomes:
measure: Change From Baseline Blink Rate
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Ocular Protection Index (OPI)
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Corneal Staining
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Conjunctival (Temporal) Staining
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Conjunctival (Nasal) Staining
timeFrame: From baseline to Day 30 (Part 3)
Other outcomes:
measure: Change From Baseline Visual Acuity
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Conjunctival Redness
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Lid Redness
timeFrame: From baseline to Day 30 (Part 3)
measure: Change From Baseline Intraocular Pressure
timeFrame: From baseline to Day 30 (Part 3)
Locations:
city: Kuopio
country: Finland
facility: Department of Ophthalmology, Kuopio University Hospital
Study officials:
affiliation: Kuopio University Hospital
name: Kai Kaarniranta, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Laihia J, Jarvinen R, Wylegala E, Kaarniranta K. Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial. Acta Ophthalmol. 2020 May;98(3):244-254. doi: 10.1111/aos.14252. Epub 2019 Oct 3.