Clinical trial NCT02503644 (phase 2, status: completed)
Conditions: scleroderma, diffuse, diffuse cutaneous systemic sclerosis
ICD codes: A06.7, A22.0, A26.0, A32.0, A36.3, A43.1, B38.3
Drugs: iva337, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Informed Consent documented by signature

          -  Systemic sclerosis according to ACR/EULAR 2103 criteria (van de Hoogen 2013)

          -  Diffuse cutaneous SSc subset according to LeRoy's criteria

          -  Diagnosis within the past 3 years as defined by the first non-Raynaud's symptom

          -  MRSS between 10 and 25

          -  Age between 18 and 75, male or female

        Patients on stable treatment (for >3 months) with prednisone ≤ 10 mg, methotrexate≤ 20
        mg/w, azathioprine ≤ 150 mg/d, mycophenolate mofetil ≤ 2g/d, or leflunomide ≤ 20 mg/d may
        be included in the study; the therapy must be maintained as background therapy.

        Exclusion Criteria:

          -  Cyclophosphamide during the past 3 months

          -  Requirement of IV prostanoids for pulmonary hypertension in the last 3 months

          -  Renal insufficiency defined by a creatinine clearance of less than 30 ml/min (CKD-EPI
             or MDRD formula) and/or past/current renal crisis

          -  Hepatic impairment i.e. primary biliary cirrhosis and unexplained persistent liver
             function abnormality,

          -  Gallbladder disease (Cholelithiasis is not an exclusion criterion)

          -  Diabetic ketoacidosis

          -  Severe cardiac (LVEF <45%) and/or pulmonary disease (FVC < 50% or pulmonary
             hypertension proven by right heart catheterisation)

          -  History of heart failure, symptomatic coronary artery disease, significant ventricular
             tachyarrhythmia, stent placement, coronary artery bypass surgery, and/or myocardial
             infarction.

          -  Recipient of solid organ transplant

          -  Gastrointestinal involvement preventing oral administration of study drug

          -  Chronic infections, positive serology for infection with hepatitis B or C.

          -  Pregnancy, Lactation. Woman of childbearing potential unwilling to use a medically
             acceptable form of birth control

          -  History of malignancy within the last 5 years, except for resected basal or squamous
             cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer

          -  A recent history of alcohol or drug abuse, non-compliance with other medical therapies

          -  Participation in a clinical study involving another investigational drug or device
             within 4 weeks before the Pre-treatment Visit

          -  Laboratory parameters at the pre-treatment visit showing any of the following abnormal
             results: transaminases > 2x the upper limit of normal (ULN) and/or bilirubin > 2x ULN;
             neutrophil count < 1,500/mm3; platelet count < 100,000/mm3; haemoglobin < 9 g/dL

          -  Known hypersensitivity or allergy to class of drugs or the investigational product

          -  Any condition or treatment, which in the opinion of the investigator, places the
             subject at unacceptable risk as a patient in the trial

          -  Co-therapy with biologics: Wash-out period: Any anti-TNF agent in the last 3-months:
             adalimumab, certolizumab, etanercept, golimumab, infliximab; abatacept and tocilizumab
             in the last 3 months; rituximab in the last 6 months.

          -  Any other significant heart disease or any clinically significant ECG abnormality
             reported by central ECG reading.