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

> Learn more about the SENSCIS® trial design

Decline in lung function (FVC)

Cyendiv® significantly reduced the annual rate of decline in forced vital capacity (FVC) by ~44% in patients with SSc-ILD.1,2 

> Find out more about the efficacy of Cyendiv® in SSc-ILD1,2

Patient subgroups 

Cyendiv® showed consistent efficacy across a variety of patient subgroups in SSc-ILD.1,2 

® works in a heterogeneous trial population">> Discover how Cyendiv® works in a heterogeneous trial population1

Footnotes

FVC, forced vital capacity; SSc-ILD, systemic sclerosis-associated interstitial lung disease.
 

SENSCIS® trial design

Cyendiv® was investigated in SENSCIS®, the largest phase 3 clinical trial to date in systemic sclerosis-associated interstitial lung disease (SSc-ILD), with 819 patients enrolled (screened) at 194 centres in 32 countries2–4

Randomized, double-blind, placebo-controlled trial design2,4

INPULSIS Trial Design
Primary and secondary endpoints1,2,4
Primary endpoint:
  • 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
Inclusion criteria1,4
SENSCIS Inclusion Criteria
Background therapy allowed, reflecting clinical practice:1,4
  • 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
Exclusion criteria1,4

 

 

P3.3_Desktop_03_exclusion-criteria
Medications excluded at randomization:1,4
  • 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
SENSCIS Trial Demographic Data
Footnotes

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

Decline in lung function (FVC)

Cyendiv® modified disease progression in systemic sclerosis-associated interstitial lung disease (SSc-ILD) by slowing decline in forced vital capacity (FVC) by ~44% over 52 weeks1,2
Decline In Lung Function (FVC) Data
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

Baseline Results Chance In FVC

The adjusted mean absolute change from baseline in FVC at week 52 was consistent with the results of annual rate of decline1

Adjusted Mean Absolute Change
The relative treatment effect on slowing FVC decline seen in SENSCIS® was consistent with results in Cyendiv® trials studying patients with idiopathic pulmonary fibrosis (IPF) and progressive fibrosing interstitial lung diseases (ILDs)1,2,5-7
3 Clinical Trials Data
Footnotes

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

Patient subgroups

Cyendiv® slowed forced vital capacity (FVC) decline in a broad range of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD)1

In the SENSCIS® trial:1
Patient Subgroups In SENSCIS Trial
Cyendiv® demonstrated a consistent treatment effect across the heterogeneous trial population reflective of typical clinical practice1
Absolute change from baseline in FVC over 52 weeks was similar for both those using and not using mycophenolate1,8
Absolute Change Data Graph
The annual rate of decline in FVC was similar for both those using and not using corticosteroids9
Rate Of Decline By Corticosteroid Use
Footnotes

ATA, anti-topoisomerase; CI, confidence interval; FVC, forced vital capacity; SE, standard error; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease.

References

  1. 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.
  2. Cyendiv® India pack insert version dated
  3. 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...
  4. 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.
  5. 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.
  6. 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.
  7. Flaherty KR, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681.
  8. 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...
  9. 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.