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

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 DED.

3. Patients with severe Sjögren's DED characterized by the following clinical 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 ≤ 5 mm/5 min.

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

8. 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'srelated DE).

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. Patients who have given written informed consent before any study-related proceduresnot part of standard medical care are performed.

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

13. Patients under treatment with topical cyclosporine (CsA), or topical ophthalmictreatments of the same class for at least 30 days before Screening Visit (Day -8).

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.,diabetes with glycemia out of range, thyroid malfunction) or judged by theInvestigator to be incompatible with the study (e.g., current systemic infections)or with a condition incompatible 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 anaesthetics 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) were excluded from participation in the studyif they met any one of the following conditions:

10. were currently pregnant or,

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

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

13. were breast-feeding or,

14. were not willing to use highly effective birth control measures, such as:combined (oestrogen and progesterone containing) hormonal contraceptivesassociated with inhibition of ovulation (oral, intravaginal, transdermal),progestogen-only hormonal contraception associated with inhibition of ovulation (oral, implantable, injectable), intrauterine device (IUD), intrauterinehormone-releasing system (IUS), bilateral tubal occlusion, vasectomisedpartner, sexual abstinence - during the entire course of and 30 days after thestudy treatment period.

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 corticosteroids, lifitegrast, autologous serum tears in either eyeduring the study (previous use not an exclusion criteria but must be discontinued atthe Screening Visit).

17. 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).

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

19. Any prior ocular surgery (including refractive, palpebral and cataract surgery) ifwithin 90 days before the Screening Visit.

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

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