A Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis

Inclusion criteria:

- Age >= 18 years

- 2013 ACR / EULAR classification criteria for SSc fulfilled

- SSc disease onset (defined by first non-Raynaud symptom) within 7 years

- SSc related Interstitial Lung Disease confirmed by HRCT; Extent of fibrotic disease in
the lung >= 10%

- FVC >= 40% of predicted normal

- DLCO 30% to 89% of predicted normal

Exclusion criteria:

- AST, ALT >1.5 x ULN

- Bilirubin >1.5 x ULN

- Creatinine clearance <30 mL/min

- Airway obstruction (pre-bronchodilator FEV1/FVC <0.7)

- Other clinically significant pulmonary abnormalities

- Significant PH

- Cardiovascular diseases

- More than 3 digital fingertip ulcers or a history of severe digital necrosis requiring
hospitalization or severe other ulcers

- Bleeding risk (such as predisposition to bleeding, fibrinolysis, full-dose
anticoagulation, high dose antiplatelet therapy, history of hemorrhagic central
nervous system (CNS) event within last year

- international normalised ratio (INR) >2, prolongation of prothrombin time (PT) and
partial thromboplastin time (PTT) by >1.5 x ULN)

- History of thrombotic event within last year

- Clinical signs of malabsorption or needing parenteral nutrition

- Previous treatment with nintedanib or pirfenidone

- Treatment with prednisone >10 mg/day, azathioprine, hydroxychloroquine, colchizine,
D-penicillamine, sulfasalazine, cyclophosphamide, rituximab, tocilizumab, abatacept,
leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and
ciclosporine A, potassium para-aminobenzoate

- Unstable background therapy with either mycophenolate mofetil or methotrexate

- Previous or planned hematopoietic stem cell transplantation

- Patients with underlying chronic liver disease (Child Pugh A, B, C hepatic impairment)