Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™).

Abstract

OBJECTIVES:

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). The pathological pathways involved in fibrogenesis in IPF and interstitial lung disease associated with systemic sclerosis (SSc-ILD) show commonalities; both involve fibroblast activation, myofibroblast accumulation and deposition of extracellular matrix. The SENSCIS™ trial is a randomised, placebo-controlled Phase III trial that will evaluate the efficacy and safety of nintedanib in patients with SSc-ILD (NCT02597933).

METHODS:

Approximately 520 patients with SSc (based on 2013 American College of Rheumatology/European League Against Rheumatism criteria) and ILD (≥10% fibrosis of the lungs, confirmed by central assessment of chest high resolution computed tomography), forced vital capacity (FVC) ≥40% predicted and diffusing capacity for carbon monoxide of 30-89% predicted will be enrolled. Patients will be randomised (1:1) to nintedanib 150 mg twice daily or placebo, stratified by the presence of anti-topoisomerase I antibody. To reflect real-world management, patients receiving prednisone (≤10 mg/day) and/or a stable dose of mycophenolate or methotrexate, will be eligible. The primary endpoint is the annual rate of decline in FVC (mL/ year) assessed over 52 weeks. Patients will remain on blinded study treatment until the last patient completes 52 weeks of treatment or for a maximum of 100 weeks of treatment. Key secondary endpoints are absolute changes from baseline in modified Rodnan skin score and St George's Respiratory Questionnaire at week 52.

RESULTS:

Recruitment for the trial began in November 2015.

CONCLUSIONS:

This trial will assess the efficacy and safety of nintedanib in patients with SSc-ILD.

• Authors: Oliver Distler, Kevin K Brown, Jörg H W Distler, Shervin Assassi, Toby M Maher, Vincent Cottin, John Varga, Carl Coeck, Martina Gahlemann, Wiebke Sauter, Hendrik Schmidt, Kristin B Highland, SENSCIS™ trial investigators
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2017 Sep-Oct Vol. 35 Suppl 106 Issue 4 Pg. 75-81 ISSN: 0392-856X [Print] Italy
• PMID: 28664834 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Indoles
• nintedanib

Topics

• Adult
• Double-Blind Method
• Humans
• Indoles (therapeutic use)
• Lung Diseases, Interstitial (drug therapy, etiology, physiopathology)
• Prospective Studies
• Research Design
• Scleroderma, Systemic (complications)
• Vital Capacity