Efficacy & trial design
SENSCIS® trial design
SENSCIS® is the largest phase 3, randomized, double-blind, placebo-controlled trial to date that investigated the efficacy and safety of Cyendiv® in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).1–3
Decline in lung function (FVC)
FVC, forced vital capacity; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
SENSCIS® trial design
- Annual rate of decline in forced vital capacity (FVC) in mL over 52 weeks
Key secondary endpoints:
- Absolute change from baseline in modified Rodnan skin score (mRSS) at week 52
- Absolute change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score at week 52
- Prednisone ≤10 mg/day and/or stable therapy with mycophenolate (mofetil or sodium) or methotrexate (≥6 months) was permitted
- In cases of clinically significant deterioration, additional therapy was allowed during the trial at the discretion of the investigator†
- Prednisone >10 mg/day or equivalent ≤2 weeks prior to randomization
- Unstable background therapy with mycophenolate or methotrexate
- Azathioprine, hydroxychloroquine, colchicine, D-penicillamine, or sulfasalazine ≤8 weeks prior to randomization
- Cyclophosphamide, rituximab, tocilizumab, abatacept, leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and cyclosporine A, or potassium para-aminobenzoate ≤6 months prior to randomization
The SENSCIS® trial population is representative of a broad range of patients with SSc-ILD1
ACR, American College of Rheumatology; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DLCO, diffusing capacity of the lung for carbon monoxide; EULAR, European League Against Rheumatism; FVC, forced vital capacity; HRCT, high-resolution computed tomography; HSCT, hematopoietic stem cell transplant; mRSS, modified Rodnan skin score; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire; SpO2, peripheral oxygen saturation; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; ULN, upper limit of normal.
* Disease onset defined as the time of the first non-Raynaud phenomenon symptom.4
† The additional (otherwise restricted) therapies permitted were mycophenolate mofetil, mycophenolate sodium, methotrexate, azathioprine, cyclophosphamide, cyclosporine A, prednisone >10 mg/day, hydroxychloroquine, colchicine, D-penicillamine, sulfasalazine, rituximab, tocilizumab, abatacept, leflunomide, tacrolimus, and newer anti-arthritic treatments such as tofacitinib and potassium para-aminobenzoate.1
‡ Defined as previous clinical or echocardiographic evidence of significant right heart failure, history of right heart catheterization showing a cardiac index ≤2 L/min/m2, or pulmonary hypertension requiring parenteral therapy with epoprostenol/treprostinil.1
Cyendiv® showed an early and sustained reduction in lung function decline over 52 weeks1
The curves for the change from baseline in FVC (mL) clearly separated by week 12 and continued to diverge up to week 521
The adjusted mean absolute change from baseline in FVC at week 52 was consistent with the results of annual rate of decline1
ATA, anti-topoisomerase; CI, confidence interval; FVC, forced vital capacity; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; SE, standard error; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
* Adjusted for fixed categorical effects of ATA status, visit, treatment-by-visit interaction, baseline-by-visit interaction, age, gender, and height.1
ATA, anti-topoisomerase; CI, confidence interval; FVC, forced vital capacity; SE, standard error; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
- Distler O, et al; the SENSCIS Trial Investigators. Nintedanib for systemic sclerosis-associated lung disease. N Engl J Med. 2019;380(26):2518-2528. doi:10.1056/NEJMoa1903076.
- Cyendiv® India pack insert version dated
- Boehringer Ingelheim. Presentations for the July 25, 2019 Meeting of the Arthritis Advisory Committee. 2019 (Accessed August 2020). Available at: https://www.fda.gov/advisory-committees/arthritis-advisory-committee/sli...
- Distler O, et al; SENSCIS™ trial investigators. Design of a randomised, placebo-controlled clinical trial of nintedanib in patients with systemic sclerosis-associated interstitial lung disease (SENSCIS™). Clin Exp Rheumatol. 2017;35(4)(suppl 106):75-81.
- Richeldi L, et al; INPULSIS® Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;380(22):2071-2082. doi:10.1056/NEJMoa1402584.
- Richeldi L, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079-1087. doi:10.1056/NEJMoa1103690.
- Flaherty KR, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681.
- Highland K, et al. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease by use of mycophenolate at baseline: Subgroup analysis of the SENSCIS trial [abstract]. Arthritis Rheumatol. 2019;71(suppl 10). (Accessed August 2020). Available at: https://acrabstracts.org/abstract/efficacy-and-safety-of-nintedanib-in-p...
- Vonk MC, et al. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS® trial by corticosteroid use. Poster presented at the ACR/ARP Annual Meeting, Atlanta, Georgia, 8–13 November 2019.