Anifrolumab Treatment for 24 Weeks in Patients With Primary Sjögren's Syndrome

Inclusion Criteria:

1. Written informed consent
2. Female or male aged ≥18 years
3. Disease duration (time since diagnosis) ≤10 years. In case of pediatric-onset pSS adisease duration of ≤15 years is allowed if there is residual gland function (UWS≥0.01or SWS≥0.1 ml/min).
4. Fulfilment of 2016 ACR-EULAR classification criteria for pSS (which includes focusscore ≥1 in salivary gland biopsy and/or anti-SSA/Ro positivity), based on previousdiagnostic examinations
5. Presence of anti-SSA antibodies
6. ESSDAI≥5 and/or ESSPRI≥5. ESSDAI≥5 implicates a moderate to high systemic diseaseactivity and ESSPRI≥5 implicates that the patient-reported symptom state isunacceptable. At least 50% of patients need to fulfil the ESSDAI≥5 criterion.Inclusion of patients with low ESSDAI (<5) should be discontinued when 15 includedpatients (50%) have a low ESSDAI.
7. Willingness to undergo a repeated parotid gland biopsy at baseline and 24 weeks afterstart treatment. If a recent parotid gland biopsy (within ≤1 year before the baselinevisit) is available, and enough material of this parotid gland biopsy is available,this biopsy can be used as baseline sample.
8. Use of reliable method of contraception for participants of reproductive potential.
9. Vaccinated against COVID-19 (at least two COVID-19 vaccinations) or previous confirmedCOVID-19 infection (from which the patient is recovered) in combination with at leastone COVID-19 vaccination or a previous confirmed COVID-19 infection (from which thepatients has recovered) in combination with a positive anti-SARS-CoV-2 antibody test.

Exclusion Criteria:

1. Presence of any other connective tissue disease
2. Positive pregnancy test (urinary HCG) at screening or breast-feeding
3. History of alcohol or drug abuse
4. History of malignancy or with a current suspicion for cancer, apart from local MALTlymphoma, squamous or basal cell carcinoma of the skin treated with documented successof curative therapy ≥3 months prior to week 0 or cervical cancer in situ treated withapparent success with curative therapy ≥1 year prior to week 0.
5. Subjects with evidence (as assessed by the investigator) of active or latent bacterialor viral infections at the time of potential enrollment, including subjects withevidence of HIV which will be tested during screening.
6. History of chronic or recurrent serious infections. (e.g. chronic pyelonephritis,osteomyelitis or bronchiectasis).
7. Subjects with serious bacterial infections within the last 3 months, unless treatedand resolved with antibiotics.
8. Opportunistic infection requiring hospitilization or IV antimicrobial treatment within 3 years of randomization
9. Any infection requiring hospitalization or treatment with IV anti-infectivemedications not completed at least 4 weeks prior to signing the ICF.
10. Subjects with herpes zoster that resolved less than 12 weeks before potentialenrollment or any severe case of herpes zoster in a subjects history, including, butnot limited to, non-cutaneous herpes (ever), herpes encephalitis (ever), recurrentherpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes involvingthe retina (ever).
11. Any clinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection that has notcompletely resolved within 12 weeks prior to signing the ICF.
12. Any history of severe COVID-19 infection (e.g. requiring hospitalization, ICU care orassisted ventilation) or any prior COVID-19 infection with unresolved sequelae. Anyacute COVID-19 infection (lab confirmed or suspected based on clinical symptoms)within the last 3 months prior to screening.
13. Subjects at risk for TB. Specifically excluded from this study will be subjects with ahistory of active TB; current clinical, radiographic, or laboratory evidence of activeTB, which will be tested during screening; history of latent TB, with the exception oflatent TB with documented completion of appropriate treatment.
14. Subjects who are positive for hepatitis B surface antigen, which will be tested duringscreening.
15. Subjects who are positive for hepatitis C antibody if the presence of hepatitis Cvirus was also shown with polymerase chain reaction or recombinant immunoblot assay,which will be tested during screening.
16. Subjects who have received any live or attenuated vaccines within 8 weeks prior tosigning the ICF.
17. Blood transfusion or receipt of blood products within 4 weeks prior to signing theICF.
18. Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal,hematological or neurological conditions, chronic or latent infectious diseases orimmune deficiency which places the patient at an unacceptable risk for participationin the study.
19. Preceding treatment with biological DMARDs, including abatacept, anti-TNF or othermonoclonal antibodies within 6 months, and rituximab within 12 months from baseline
20. Use of high-dose prednisone, less than 2 weeks before inclusion. Stable low dose (≤10mg) is allowed.
21. Use of hydroxychloroquine, methotrexate, cyclophosphamide, cyclosporine, azathioprine,MMF and leflunomide less than 3 months ago.
22. Use of pilocarpine less than 1 month ago.
23. Lab abnormalities:

• Serum creatinine > 2.8 mg/dl (250 μmol/l)
• ASAT or ALAT outside 2.5 x upper normal range of the laboratory
• Hb < 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
• Neutrophil granulocytes less than 0.5 x 109/l
• Platelet count less than 50 x 109/l

24. Any other laboratory test results that, in the opinion of the investigator, mightplace a subject at unacceptable risk for participation in the study.
25. A known history of allergy or reaction to any component of the IP formulation orhistory of anaphylaxis to any human gamma globuline therapy.
26. Involvement in the planning and/or conduct of the study (applies to both Investigatorstaff and/or staff at the study site)
27. Previous enrolment or randomisation in the present study
28. Participation in another clinical study with an investigational drug during the last 6months, or local investigational product during the last month