Safety and Efficacy of Itacitinib in Adults with Systemic Sclerosis

Inclusion Criteria:

• Adult patient (≥18 years old)

• Patient with a diagnosis of diffuse SSc, as defined by the American College ofRheumatology / EULAR 2013 criteria,

• Patient with a diffuse SSc, according to Leroy and Medsger dichotomy

• Patient with a SSc disease duration of less than 36 months (defined as time fromfirst non-Raynaud phenomenon manifestation) or with an active SSc disease, asdefined by EUSTAR disease activity score,

• Patient with a modified Rodnan skin score (mRSS) ≥ 10 and ≤ 35 units at screening,

• Negative pregnancy test for woman of childbearing potential, woman of childbearingpotential should have reliable contraception for the 12 months' duration of thestudy,

• Patient able to give written informed consent prior to participation in the study,

• Affiliation to a social security scheme (profit or being entitled)

• If patients receive mycophenolate or methotrexate for SSc, these need to be onstable dose as follows:

• Mycophenolate mofetil/sodium: stable dose for at least 2 months prior torandomisation

• Methotrexate: stable dose and route of administration for at least 2 monthsprior to randomisation

Exclusion Criteria:

• Previous treatment with itacitinib or a Janus kinase (JAK) inhibitor,

• Contra-indications to itacitinib or Janus kinase inhibitor,

• Failure to sign the informed consent or unable to consent

• Patient participating in another investigational therapeutic study,

• Acute or chronic active infections, including HBV, HCV, HIV,

• Patient with other uncontrolled diseases, including drug or alcohol abuse, severepsychiatric diseases, that could interfere with participation in the trial accordingto the protocol,

• Patient suspected not to be observant to the proposed treatments,

• Patient who have white blood cell count ≤ 4,000/mm3,

• Patient who have platelet count ≤ 100,000/mm3,

• Patients who have ALT or AST level greater that 3 times the upper limit of normal,

• Patient who have triglyceride level greater than 5g/L

• Pregnant or breastfeeding woman,

• Protected adults (including individual under guardianship by court order),

• Patient receiving or having received cyclophosphamide or rituximab within the lastthree months (possible inclusion beyond 3 months),

• Patient receiving or having received a biotherapy (anti-TNF, abatacept ortocilizumab) in the last 3 months (possible inclusion beyond 3 months)

• Patient with Systemic Lupus, or Sjögren's syndrome with systemic manifestationsjustifying immunosuppressive therapy

• Atherosclerotic cardiovascular disease as defined by a history of myocardialinfarction, ischaemic stroke, or peripheral artery thrombosis

• Anti-phospholipid syndrome