Safety and Efficacy Study on Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (PROTEGO-1 Study)

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 Dry Eye Disease (DED).
• Patients with severe Sjögren's dry eye disease 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 ≤5mm/5min
• The same eye (eligible eye) must fulfill all the above criteria
• Patients diagnosed with severe Sjögren's dry eye disease at least 3 months before enrolment
• 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.
• Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent Form signed by patients and/or legal representative must have been approved by the IRB/IEC for the current study
• Patients must have the ability and willingness to comply with study procedures.

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 anesthetics 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) are excluded from participation in the study if they meet any one of the following conditions:
• are currently pregnant or,
• have a positive result at the urine pregnancy test (Baseline/Day 1) or,
• intend to become pregnant during the study treatment period or,
• are breast-feeding or,
• are not willing to use highly effective birth control measures

During the entire course of and 30 days after the study treatment periods

• Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
• Use of topical cyclosporine, or topical ophthalmic treatments of the same class, within 14 days of screening visit (day -8)
• Use of topical corticosteroids, lifitegrast, autologous serum tears in either eye during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
• Contact lenses, True Tear device, moistur