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

Inclusion Criteria:

1. Male or female aged ≥ 18 years

2. Patients with a confirmed diagnosis of Sjögren's syndrome or other autoimmunedisease known to induce Sjögren's Dry Eye Disease (DED).

3. Patients with severe Sjögren's dry eye disease characterized by the followingclinical features:

4. Corneal and/or conjunctival staining with fluorescein using National EyeInstitute (NEI) grading system ≥3

5. SANDE questionnaire >25 mm

6. Schirmer test I (without anaesthesia) ≥2 ≤5mm/5min

7. The same eye (eligible eye) must fulfill all the above criteria

8. Patients diagnosed with severe Sjögren's dry eye disease at least 3 months beforeenrolment

9. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200Snellen value) in each eye at the time of study enrolment

10. If a female of childbearing potential, have a negative urine pregnancy test and usea highly effective method to avoid pregnancy for the duration of the trial and 30days after the study treatment period. Males of reproductive potential should useeffective contraception during treatment and 30 days after the study treatmentperiod.

11. Only patients who satisfy all Informed Consent requirements may be included in thestudy. The patient and/or his/her legal representative must read, sign and date theInformed Consent document before any study-related procedures are performed. TheInformed Consent Form signed by patients and/or legal representative must have beenapproved by the IRB/IEC for the current study

12. Patients must have the ability and willingness to comply with study procedures.

Exclusion Criteria:

1. Inability to speak and understand the local language sufficiently to understand thenature of the study, to provide written informed consent, and to allow thecompletion of all study assessments

2. Evidence of an active ocular infection, in either eye

3. Presence of any other ocular disorder or condition requiring topical medicationduring the entire duration of study in either eye

4. History of severe systemic allergy or of ocular allergy (including seasonalconjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye

5. Intraocular inflammation defined as Tyndall score >0

6. History of malignancy in the last 5 years

7. Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabeteswith glycemia out of range, thyroid malfunction) or judged by the investigator to beincompatible with the study (e.g. current systemic infections) or with a conditionincompatible with the frequent assessment required by the study

8. Patient had a serious adverse reaction or significant hypersensitivity to any drugor chemically related compounds or had a clinically significant allergy to drugs,foods, amide local anesthetics or other materials including commercial artificialtears (in the opinion of the investigator).

9. Females of childbearing potential (those who are not surgically sterilized orpost-menopausal for at least 1 year) are excluded from participation in the study ifthey meet any one of the following conditions:

10. are currently pregnant or,

11. have a positive result at the urine pregnancy test (Baseline/Day 1) or,

12. intend to become pregnant during the study treatment period or,

13. are breast-feeding or,

14. are not willing to use highly effective birth control measures During the entire course of and 30 days after the study treatment periods

15. Any concurrent medical condition, that in the judgment of the PI, might interferewith the conduct of the study, confound the interpretation of the study results, orendanger the patient's well-being

16. Use of topical cyclosporine, or topical ophthalmic treatments of the same class,within 14 days of screening visit (day -8)

17. Use of topical corticosteroids, lifitegrast, autologous serum tears in either eyeduring the study (previous use not an exclusion criteria but must be discontinued atthe screening visit)

18. Contact lenses, True Tear device, moisture goggles, sutureless amniotic membrane orpunctum plug use during the study (previous use not an exclusion criteria but mustbe discontinued at the screening visit)

19. History of drug addiction or alcohol abuse in the last 2 years

20. Any prior ocular surgery (including refractive, palpebral and cataract surgery) ifwithin 90 days before the screening visit

21. Participation in a clinical trial with a new active substance during the past 3months

22. Participation in another clinical trial study at the same time as the present study.