A Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis
Condition: Scleroderma, Systemic
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse
Intervention: Nintedanib; Placebo
Intervention MeSH terms: Nintedanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 580.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Systemic Sclerosis (SSc) is a devastating disease of unknown etiology. Patients suffer from
      multiple organ fibrosis whereas lung fibrosis (interstitial lung disease, ILD) is one of the
      main driver for mortality. There is preclinical evidence for efficacy of nintedanib in SSc
      and associated ILD (SSc-ILD) and the anti-fibrotic efficacy of nintedanib was proven in
      idiopathic pulmonary fibrosis patients, who are presenting a similar pattern regarding lung
      fibrosis. Hence it is the purpose of the trial to confirm the efficacy and safety of
      nintedanib 150 mg bid in treating patients with SSc-ILD, compared with placebo. The trial
      will be conducted as a double blind, randomised, placebo-controlled trial with primary
      efficacy evaluation at week 52 and placebo-controlled treatment until last patient out (up to
      a maximum of 100 weeks). Respiratory function is globally accepted for assessment of
      treatment effects in patients with lung fibrosis. The chosen endpoint (Forced Vital Capacity
      (FVC) decline) is easy to obtain and is part of the usual examinations done in patients with
      SSc-ILD.
    

Eligibility criteria:

        Inclusion criteria:

          -  Age >= 18 years

          -  2013 American College of Rheumatology (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 High Resolution Computer Tomography
             (HRCT); Extent of fibrotic disease in the lung >= 10%

          -  FVC >= 40% of predicted normal

          -  Carbon Monoxide Diffusion Capacity (DLCO) 30% to 89% of predicted normal

        Exclusion criteria:

          -  Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) >1.5 x ULN

          -  Bilirubin >1.5 x ULN

          -  Creatinine clearance <30 mL/min

          -  Airway obstruction (pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC
             <0.7)

          -  Other clinically significant pulmonary abnormalities

          -  Significant Pulmonary Hypertension (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, colchicine,
             D-penicillamine, sulfasalazine, cyclophosphamide, rituximab, tocilizumab, abatacept,
             leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and
             cyclosporine 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)