Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease

Inclusion Criteria

• Male or female aged ≥ 18 years.
• Patients with a confirmed diagnosis of Sjögren's syndrome or other autoimmune disease known to induce Sjögren's DED.
• Patients with severe Sjögren's DED characterized by the following clinical features:
• Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system ≥ 3.
• SANDE questionnaire >25 mm.
• Schirmer test I (without anaesthesia) ≥ 2 ≤ 5 mm/5 min.
• The same eye (eligible eye) must fulfil all the above criteria.
• Patients diagnosed with severe Sjögren's DED at least 3 months before enrolment (current use or recommended use of artificial tears for the treatment of Sjögren's related DE).
• Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in each eye at the time of study enrolment.
• If a female of childbearing potential, have a negative urine pregnancy test and use a highly effective method to avoid pregnancy for the duration of the trial and 30 days after the study treatment period. Males of reproductive potential should use effective contraception during treatment and 30 days after the study treatment period.
• Patients who have given written informed consent before any study-related procedures not part of standard medical care are performed.
• Patients must have the ability and willingness to comply with study procedures.
• Patients under treatment with topical cyclosporine (CsA), or topical ophthalmic treatments of the same class for at least 30 days before Screening Visit (Day -8).

Exclusion Criteria

• Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments.
• Evidence of an active ocular infection, in either eye.
• Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study in either eye.
• History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye.
• Intraocular inflammation defined as Tyndall score > 0.
• History of malignancy in the last 5 years.
• Systemic disease not stabilized within 1 month before Screening Visit (e.g., diabetes with glycemia out of range, thyroid malfunction) or judged by the Investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study.
• Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anaesthetics or other materials including commercial artificial tears (in the opinion of the Investigator).
• Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) were excluded from participation in the study if they met any one of the following conditions:
• were currently pregnant or,
• had a positive result at the urine pregnancy test (Baseline/Day 1) or,
• intended to become pregnant during the study treatment period or,
• were breast-feeding or,
• were not willing to use highly effective birth control measures, such as: combined (oestrogen and progesterone containing) hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, implantable, injectable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence - during the entire course of and 30 days after the study treatment period.
• Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the stud