A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study
| Autor: | Dale W. Usner, Thomas Schlüter, George W Ousler, Joseph B. Ciolino, Blair E. Boehmer, Eugene B McLaurin, David Wirta, John D. Sheppard, Sonja Krösser, Meides Alice |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Active Comparator Adolescent Phases of clinical research Administration Ophthalmic corneal staining Cornea Quality of life Double-Blind Method Ophthalmology medicine visual function Humans Prospective Studies cyclosporine Lead (electronics) DED Corneal epithelium Aged Fluorescent Dyes Aged 80 and over semi-fluorinated alkane Staining and Labeling business.industry conjunctival staining Water dryness score Middle Aged Clinical Science eye diseases Bioavailability medicine.anatomical_structure Treatment Outcome Tolerability Dry Eye Syndromes Female Fluorescein Ophthalmic Solutions business Conjunctiva Immunosuppressive Agents |
| Zdroj: | Cornea |
| ISSN: | 1536-4798 |
| Popis: | Dry eye disease (DED) is defined by the International Dry Eye Workshop (TFOS DEWS II) as a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.1 In DED patients, activities requiring prolonged gazing with involuntary suppression of blinking can lead to ocular surface irregularities and corneal epithelium damage,2 both affecting visual function3 and eventually preventing patients from performing basic activities of daily life such as reading, driving, or working with screens.4 Consequently, DED negatively impacts quality of life comparable with other severe diseases.5 Recently, the impact of DED on reading speed has been increasingly investigated,6–11 suggesting that reading speed might be substantially affected by the level of corneal staining, especially under straining conditions in daily life such as prolonged duration of reading. The treatment under investigation, CyclASol 0.1%, is a clear topical water-free ophthalmic solution of cyclosporine A in a novel vehicle, the semifluorinated alkane (SFA)-based EyeSol technology, using the SFA perfluorobutylpentane (abbreviated F4H5). This topical formulation was developed for the treatment of DED with the goal of increasing local bioavailability, avoiding the use of oils, surfactants, and preservatives. Cyclosporine A is an antiinflammatory agent with immunomodulatory properties with proven efficacy in DED.12 Potential benefits of the CyclASol 0.1% formulation in a water-free SFA solution include improved tolerability and decreased visual disturbance compared with typical cyclosporine A formulations, which frequently involve surfactants and oils. A further potential benefit is an improved clinical efficacy because of better local bioavailability. CyclASol has been investigated previously in one phase 1 clinical study with healthy volunteers and one phase 2 clinical study in patients with DED. Both clinical studies showed an excellent tolerability and safety profile. The CyclASol phase 2 study was a randomized, double-masked, vehicle-controlled, dose finding study with CyclASol 0.05% and CyclASol 0.1% and an open-label active comparator and showed a consistent reduction in corneal and conjunctival staining after treatment with CyclASol compared with the vehicle and with the active comparator, with an early onset of effect as of week 2.13 The central area of the cornea, which is an important region relevant to visual function, benefitted most. Thus, reading assessments were included in the present phase 2B/3 study. The treatment effect on cornea staining parameters was more pronounced in patients with higher baseline values of total corneal fluorescein staining (CFS). Therefore, patients with total CFS scores ≥10 [National Eye Institute (NEI) scale] at baseline were chosen for the confirmatory clinical phase 2B/3 study. The 0.1% concentration was selected for its trend toward a better effect on symptoms in the target population. This work presents the results of the phase 2B/3 study CYS-003 (ESSENCE) designed to confirm the efficacy, safety, and tolerability of CyclASol 0.1% ophthalmic solution in comparison with its vehicle (F4H5) for the treatment of signs and symptoms of DED. |
| Databáze: | OpenAIRE |
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