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Ophthalmology. 2019 Jan 28. pii: S0161-6420(18)32132-8. doi: 10.1016/j.ophtha.2019.01.024. [Epub ahead of print]

A Clinical Phase 2 Study to Assess Efficacy, Safety and Tolerability of CyclASol® for Treatment of Dry Eye Disease (DED).

Author information

1
Eye Research Foundation, Newport Beach, USA.
2
Andover Eye Associates, Andover, USA.
3
MedRACS, LLC., Quincy, USA.
4
Central Maine Eye Care, Lewiston, USA.
5
Massachusetts Eye and Ear Infirmary / Harvard Medical School, Boston, USA.
6
BAST, Heidelberg, Germany.
7
CaRACS Berlin, Germany.
8
Ora, Andover, USA.
9
Department of Ophthalmology, Medical Faculty, University of Cologne, Germany.
10
Novaliq GmbH, Heidelberg, Germany.

Abstract

PURPOSE:

To compare the efficacy, safety and tolerability of CyclASol® at two concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with Dry Eye Disease (DED). An open-label RestasisTM arm was included to allow a direct comparison with an approved therapy.

DESIGN:

An exploratory Phase 2, multicenter, randomized, vehicle controlled clinical trial, double-masked between CyclASol® and vehicle with an open-label comparator.

PARTICIPANTS:

Two hundred and seven eligible patients with a history of dry eye were randomized 1:1:1:1 to one of four treatment arms (CyclASol® 0.05%, n=51; CyclASol® 0.1%, n=51; vehicle, n=52 and RestasisTM, n=53).

METHODS:

After a 2-week run-in period with twice daily dosing of SystaneTM Balance, patients were randomized to the respective treatment arm and dosed twice daily for 16-weeks.

MAIN OUTCOME MEASURES:

The study was set up to explore efficacy on a number of sign and symptom endpoints including total and sub-region corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity and Ocular Surface Disease Index (OSDI©) questionnaire.

RESULTS:

CyclASol showed a consistent reduction in corneal and conjunctival staining compared to both vehicle and Restasis over the 16-week treatment period with an early onset of effect (at day 14). A mixed-effect-model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining p<0.1, central corneal staining p<0.001, conjunctival staining p<0.01). This model-based analysis suggests a significant CyclASol effect for OSDI© as symptom parameter (p<0.01). The number of ocular AEs were low in all treatment groups.

CONCLUSIONS:

CyclASol® showed efficacy, safety and tolerability at two concentrations in moderate to severe DED. In a direct head to head against open-label RestasisTM, CyclASol® was found to have an earlier onset of action, as early as after two weeks of treatment in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.

PMID:
30703441
DOI:
10.1016/j.ophtha.2019.01.024
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