Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis

Prior treatment

• Previous treatment with itacitinib or a Janus kinase (JAK) inhibitor,
• Contra-indications to itacitinib or Janus kinase inhibitor,
• Patient receiving or having received cyclophosphamide or rituximab within the last three months (possible inclusion beyond 3 months),
• Patient receiving or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)

Other illness

• Failure to sign the informed consent or unable to consent
• Acute or chronic active infections, including HBV, HCV, HIV,
• Patient with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
• Patient with Systemic Lupus, or Sjögren's syndrome with systemic manifestations justifying immunosuppressive therapy
• Atherosclerotic cardiovascular disease as defined by a history of myocardial infarction, ischaemic stroke, or peripheral artery thrombosis
• Anti-phospholipid syndrome

Lab values

• 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,

Other

• Patient participating in another investigational therapeutic study,
• Patient suspected not to be observant to the proposed treatments,
• Patient who have triglyceride level greater than 5g/L
• Pregnant or breastfeeding woman,
• Protected adults (including individual under guardianship by court order),

• Adult patient (≥18 years old)
• Patient with a diagnosis of diffuse SSc, as defined by the American College of Rheumatology / 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 from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined 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 childbearing potential should have reliable contraception for the 12 months' duration of the study,
• 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 on stable dose as follows:
  • Mycophenolate mofetil/sodium: stable dose for at least 2 months prior to randomisation
  • Methotrexate: stable dose and route of administration for at least 2 months prior to randomisation