To Demonstrate the Non-inferiority of Eyestil Protection® Compared to Vismed® in Terms of Clinical Performance

A Prospective Multicenter, Comparative, Randomized, Single-blind, Non-inferiority Study of Eyestil Protection® Unidose Versus Vismed® Unidose in Patients With Moderate to Severe Dry Eye Syndrome

This is a national, prospective, multicenter, comparative, randomized, single-blinded non-inferiority study performed in two parallel groups.

3 months (plus a run in period of 15 days prior inclusion) Patients with moderate to severe dry eye syndrome.

Public hospitals and private practices specialized in ophthalmology Approximately 10 sites France Approximately 80 patients globally: 40 per arm with a 1:1 ratio including an expected dropout rate of 15%.

Dry eye has been defined 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 the tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.

However, prevalence estimates for dry eye vary dramatically from 5% to 50% due to the various operational definitions of dry eye used and the characteristics of the population studied.

The available evidence suggests also that dry eye has a negative impact on overall quality of life. It causes pain and irritation and affects ocular and general health and well-being, the perception of visual function and visual performance. Reduced quality of life in everyday activities and leisure pursuits is reported by 60% of patients, while 38% of patients complain of reduced efficiency at work.

Therefore, the economic burden and impact of dry eye on vision and quality of life, work productivity, psychological and physical impact of pain are considerable. As a consequence, dry eye represents a public health burden. However, only a handful of therapies are available for dry eye patient and are used according to the disease severity.

In such context, SIFI SpA. has developed Eyestil Protection® (or SF-104 XNT Single dose). It is a sterile preservative-free device (eye drops) for ophthalmic use containing 0.2% xanthan gum, presented in 0.3 ml unidose containers. The main action of Eyestil Protection is to lubricate and moisturize the ocular surface as well as to protect it from oxidative stress thanks to the anti-oxidative properties of the xanthan gum (as demonstrated by in-vitro studies (Amico, Tornetta et al. 2015). It is indicated in all cases of dry-eye related ocular discomfort and to relief ocular discomfort due to the use of contact lenses.

Eyestil Protection® unidose is CE marked but is not available yet in all European countries, notably in France.

Confronted to a European regulatory change on medical devices - from a Directive (Directive 1993/42/EEC) to a Regulation (MDR 2017/745) that now requires clinical evidence of device performance and safety; SIFI SpA decided to implement the present clinical comparative performance study. The choice of Vismed® (unidose) as the comparator has been done since it is the current French standard of care treatment for patients with moderate to severe dry eyes.

Primary objective

• To demonstrate the non-inferiority of Eyestil Protection® compared to Vismed® in terms of clinical performance as detected by a reduction of keratitis lesions objectified by staining tests after 1 month of treatment, in patients with moderate to severe dry eye syndrome with keratoconjunctivitis.

Secondary objectives Clinical performance

• To evaluate the tear film stability per group as objectified by the tear break up time (TBUT) test at month 1 and 3;
• To evaluate the long term clinical performance of Eyestil Protection® compared to Vismed® as detected by a reduction of keratitis lesions objectified by staining tests after 3 months of treatment;
• To evaluate the tear production per group as objectified by the Schirmer test at month 3.

Patient reported outcomes

• To compare patients reported outcomes (PRO) measures per group at month 1 and 3, including:

  • Patient's reported symptoms and
  • Patient's quality of life (QoL). Investigator overall satisfaction

• To assess investigator's overall satisfaction of the treatment's clinical performance at month 1 and 3.

Safety • To describe the safety profile of Eyestil Protection® compared to Vismed® after 3 months of treatment.

Exploratory objectives

• To compare patient's QoL subscale scores per group at each time point.

Inclusion Criteria:

• Adult patients, male or female, of at least 18 years of age at the screening visit
• Patients understanding the study, willing to follow the instructions and providing their written Informed Consent Form to participate
• Patients with moderate up severe dry eye with keratoconjunctivitis sicca diagnosed at least 4 weeks before the screening visit
• Patients using artificial tears at least once a day for at least 4 weeks before the screening visit
• Patients with corneal/conjunctival lesions consistent with a diagnosis of keratoconjunctivitis measured by tests of staining: i.e. the overall score of the corneal staining test must be ≥ 3 and ≤ 9 on the 15-point Oxford scale
• And at least one of the following element: Tear volume decreased: must be either present a Schirmer test ≥ 3 mm and ≤ 9 mm / 5 minutes or the sum of 3 consecutive measurements of the tear film break-up time (TBUT) ≤ 30s for at least one eye;
• OSDI score ≥18
• Covered by healthcare insurance.

Exclusion Criteria:

• Patients with medical history of herpetic keratitis, peripheral ulcerative keratitis, sclerites, diabetic retinopathy
• Any systemic disease that is not well controlled for at least 2 months (e.g. lupus, rheumatoid arthritis, thyroiditis…) according to clinical judgment
• Patients using any topical therapies such as non-steroidal anti-inflammatory drugs, cortisone, cyclosporine, vasoconstrictor
• Patients with at least one of the following concomitant ocular inflammatory disease: Stevens Johnson Disease, Atopic Keratoconjunctivitis; Scarlet Eye Pemphigoid
• Patients with anomalies of the eyelid, sucking, infectious conjunctivitis, pterygia, and/or a glaucoma treated with eyedrops
• Presence of graft versus host disease (GVHD)
• Patients who have undergone surgery in the eye, within three months before the study enrolment
• Patients who have undergone corneal transplantation or refractive surgery or plan to undergo any eye surgery in the next four months
• Patients with known or suspected eye allergy
• Patients with a condition or history that, in the opinion of the investigator, may interfere significantly with the subject's participation in the study
• Female pregnant, planning a pregnancy during the study period and nursing an infant
• Patients who are participating or have participated in other clinical trial with investigational drug or device within 30 days prior to screening
• Patients unable to be compliant with the study procedures and requirements, according to the opinion of the investigator
• Patient deprived of liberty by a judicial or administrative decision, or who is under a measure of legal protection (e.g. guardianship or curatorship)