Proof-of-concept Trial of IVA337 in Diffuse Cutaneous Systemic Sclerosis

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.