Phase 3
Completed N=580
A Trial to Compare Nintedanib With Placebo for Patients With Scleroderma Related Lung Fibrosis
Scleroderma, Systemic
Source: ClinicalTrials.gov NCT02597933 ↗
Enrolled (actual)
580
Serious AEs
29.0%
Results posted
Dec 2019
Primary outcomePrimary: Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks — -93.3; -52.4 millilitre (mL)/year (yr) — p=0.0350
◆ Published Evidence
Established
33citations · ~11 / year
Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial.
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.
Linked Publications (5)
-
Extent of fibrosis and lung function decline in patients with systemic sclerosis and interstitial lung disease: data from the SENSCIS trial.
-
Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease.
-
Risk of Malnutrition in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease Treated With Nintedanib in the Randomized, Placebo-Controlled SENSCIS Trial.
-
Outcomes in Systemic Sclerosis-Associated Interstitial Lung Disease Based on Serological Profiles With a Focus on Anticentromere and Anti-RNA Polymerase III Antibodies.
-
Nailfold capillaroscopy in patients with systemic sclerosis-associated interstitial lung disease: a substudy of the SENSCIS trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks |
-93.3; -52.4 | 0.0350 sig |
| SECONDARY Absolute Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52 |
-1.96; -2.17 | 0.5785 |
| SECONDARY Absolute Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 52. |
-0.88; 0.81 | 0.1711 |
| SECONDARY Annual Rate of Decline in FVC in Percentage (%) Predicted Over 52 Weeks |
-2.6; -1.4 | 0.0331 sig |
| SECONDARY Absolute Change From Baseline in FVC in mL at Week 52 |
-101.03; -54.63 | 0.0177 sig |
| SECONDARY Relative Change From Baseline [%] of mRSS at Week 52 |
-3.92; -10.20 | 0.4547 |
| SECONDARY Time to Death |
9; 10 | 0.7535 |
| SECONDARY The Percentage (%) of Responder Based on Combined Response Index in Systemic Sclerosis (CRISS) at Week 52 |
11.8; 12.2 | 0.9115 |
| SECONDARY Absolute Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) in % Predicted at Week 52 |
-2.77; -3.21 | 0.5668 |
| SECONDARY Absolute Change From Baseline in Digital Ulcer Net Burden at Week 52 |
0.06; 0.03 | 0.5914 |
| SECONDARY Absolute Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 |
0.022; 0.054 | 0.3447 |
| SECONDARY Absolute Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnoea Score at Week 52 |
0.34; 0.99 | 0.2727 |
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 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)
Data sourced from ClinicalTrials.gov (NCT02597933) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.