A trial to compare nintedanib with placebo for patients with scleroderma related lung fibrosis

Phase 1

• Conditions: Patients with Systemic Sclerosis and associated Interstitial Lung Disease; MedDRA version: 20.0Level: LLTClassification code 10012977Term: Diffuse systemic sclerosisSystem Organ Class: 100000004859; MedDRA version: 20.0Level: LLTClassification code 10036814Term: Progressive systemic sclerosisSystem Organ Class: 100000004859; MedDRA version: 20.0Level: PTClassification code 10042954Term: Systemic sclerosis pulmonarySystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.0Level: LLTClassification code 10025109Term: Lung involvement in systemic sclerosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.0Level: LLTClassification code 10042953Term: Systemic sclerosisSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2015-000392-28-BE
• Lead Sponsor: SCS Boehringer Ingelheim Comm. V

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-25
• Study Completion: 2018-11-28
• Last Update Posted: 4 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 819

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

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

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 pulmonary hypertension
- Cardiovascular diseases
- More than 3 digital fingertip 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)
- Patients with a history of Scleroderma Renal Crisis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate a reduction in the annual rate of decline in FVC in mL over 52 weeks;Secondary Objective: To demonstrate efficacy in regard to skin fibrosis at week 52 and to demonstrate an improvement of patient's symptoms at week 52;Primary end point(s): 1: Annual rate of decline in FVC in mL<br><br>;Timepoint(s) of evaluation of this end point: 1: 52 weeks<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1: Absolute change from baseline in the mRSS<br>2: Absolute change from baseline in SGRQ total score<br>3: Annual rate of decline in FVC in percent predicted<br>4: Absolute change from baseline in FVC in mL<br>5: Relative change from baseline (%) of mRSS<br>6: Time to all-cause mortality<br>7: Absolute change from baseline at week 52 in CRISS index score<br>8: Absolute change from baseline in DLCO in percent predicted<br>9: Absolute change from baseline in digital ulcer net burden<br>10: Absolute change from baseline in HAQ-DI score<br>11: Absolute change from baseline in FACIT dyspnoea score<br>;Timepoint(s) of evaluation of this end point: 1: 52 weeks<br>2: 52 weeks<br>3: 52 weeks<br>4: 52 weeks<br>5: 52 weeks<br>6: 52 weeks<br>7: 52 weeks<br>8: 52 weeks<br>9: 52 weeks<br>10: 52 weeks<br>11: 52 weeks<br>