SENSCIS® enrolled 580 patients across 32 countries around the globe1,2
SENSCIS® WAS A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIAL OVER 52 WEEKS IN PATIENTS WITH SSc-ILD1,2
SENSCIS®1,2
Primary endpoint1,2
- Annual rate of decline in FVC over 52 weeks (measured in mL/year)
SENSCIS® RECRUITED A RANGE OF PATIENTS WITH SSc-ILD
Key inclusion criteria1,2
- Age ≥18 years
- Diagnosis of SSc with disease onset <7 years from screening†
- HRCT performed within 12 months with ≥10% extent of fibrosis
- FVC ≥40% of predicted value (no upper limit)
- DLCO 30%–89% of predicted value
Exclusion criteria1,2
- Had AST, ALT, or bilirubin >1.5 times ULN
- Bleeding risk (eg, requiring full-dose therapeutic anticoagulation)
- History of myocardial infarction
- History of stroke
- >3 digital ulcers or history of severe digital necrosis requiring hospitalization
- Significant pulmonary hypertension
- History of scleroderma renal crisis
Patients were also excluded if they received other investigational therapy, azathioprine within 8 weeks prior to randomization, or cyclophosphamide or cyclosporine A within 6 months prior to randomization, or previous treatment with nintedanib or pirfenidone. Women who were pregnant, nursing, or who planned to become pregnant while in the trial, and women of childbearing potential not willing or able to use highly effective methods of birth control for 28 days prior to and 3 months after nintedanib administration were excluded.
Co-medication allowed in the trial2
- Treatment with prednisone ≤10 mg/day or equivalent
- Stable dose of mycophenolate or methotrexate
- In cases of clinically significant deterioration, additional therapy was allowed during the trial at the discretion of the investigator
THE TRIAL POPULATION WAS REPRESENTATIVE OF PATIENTS WITH SSc-ILD SEEN IN CLINICAL PRACTICE2
Key demographic and baseline characteristics
Demographics
| OFEV (n=288) | Placebo (n=288) | |
|---|---|---|
| Mean age, years (SD) | 54.6 (11.8) | 53.4 (12.6) |
| Female sex, % | 76.7 | 73.6 |
| White, % | 69.8 | 64.6 |
| Asian, % | 21.5 | 28.1 |
| Black, % | 6.9 | 5.6 |
Lung function
| OFEV (n=288) | Placebo (n=288) | |
|---|---|---|
| Mean FVC, mL (SD) | 2459 (736) | 2541 (816) |
| Mean FVC, % predicted (SD) | 72.4 (16.8) | 72.7 (16.6) |
| DLCO, % predicted (SD) | 52.9 (15.1) | 53.2 (15.1) |
| Extent of fibrosis on HRCT, % (SD) | 36.8 (21.8) | 35.2 (20.7) |
SSc characteristics
| OFEV (n=288) | Placebo (n=288) | |
|---|---|---|
Median time since onset of first non–Raynaud’s symptom, years (SD) | 3.4 (0.3, 7.1) | 3.5 (0.4, 7.2) |
| SSc subtype: dcSSc, % | 53.1 (n=153) | 50.7 (n=144) |
| SSc subtype: lcSSc, % | 46.9 (n=135) | 49.3 (n=142) |
| ATA positive, %‡ | 60.1 | 61.5 |
Concomitant medication
| OFEV (n=288) | Placebo (n=288) | |
|---|---|---|
| Background mycophenolate use, % | 48.3 | 48.6 |
| Background methotrexate use, % | 8.0 | 5.2 |
* Primary endpoint was assessed at 52 weeks.1
† Disease onset defined as the time of the first non–Raynaud phenomenon symptom.2
‡ Historical information on anti-topoisomerase antibody status was used, or, if this information was not available to the sites, it was provided by a central laboratory.2
OFEV is proven to slow the rate of decline in pulmonary function in patients with SSc-ILD1,2
OFEV SIGNIFICANTLY REDUCED THE ANNUAL RATE OF FVC DECLINE BY 44% VS PLACEBO IN PATIENTS WITH SSc-ILD1,2§
SENSCIS®1,2
§ The annual rate of decline in FVC (mL/year) was analyzed using a random coefficient regression model.1
The safety and tolerability profile of OFEV has been demonstrated in a clinical trial with over 500 patients with SSc-ILD1
Adverse reactions reported in ≥5% of OFEV-treated patients and more commonly than placebo1
| OFEV (n=288) | Placebo (n=288) | |
|---|---|---|
| Diarrhea | 76% | 32% |
| Nausea | 32% | 14% |
| Vomiting | 25% | 10% |
| Skin ulcer | 18% | 17% |
| Abdominal pain|| | 18% | 11% |
| Liver enzyme elevation¶ | 13% | 3% |
| Weight decreased | 12% | 4% |
| Fatigue | 11% | 7% |
| Decreased appetite | 9% | 4% |
| Headache | 9% | 8% |
| Pyrexia | 6% | 5% |
| Back pain | 6% | 4% |
| Dizziness | 6% | 4% |
| Hypertension | 5% | 2% |
- The incidence of infections and infestations was similar in the OFEV and placebo groups across trials (TOMORROW, INPULSIS®-1, and INPULSIS®-2: 56% vs 55%, respectively; INBUILD®: 53% vs 56%, respectively; and SENSCIS®: 63% vs 64%, respectively)3
- The most frequent serious adverse events reported in patients treated with OFEV, more than placebo, were ILD (2.4% OFEV vs 1.7% placebo) and pneumonia (2.8% OFEV vs 0.3% placebo)1
- In addition, alopecia was reported in patients treated with OFEV, more than placebo (1.4% vs 1.0%)1
|| Includes abdominal pain, abdominal pain upper, abdominal pain lower, and esophageal pain.1
¶ Includes alanine aminotransferase increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, hepatic enzyme increased, blood alkaline phosphatase increased, transaminase increased, and hepatic function abnormal.1
THE MOST COMMON ADVERSE REACTIONS WERE GASTROINTESTINAL IN NATURE AND GENERALLY OF MILD OR MODERATE INTENSITY1
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATA, anti-topoisomerase antibodies; dcSSc, diffuse cutaneous systemic sclerosis; DLCO, diffusing capacity of the lungs for carbon monoxide; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ILD, interstitial lung disease; lcSSc, limited cutaneous systemic sclerosis; SD, standard deviation; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; ULN, upper limit of normal.
References
-
Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079-1087.
-
Distler O, et al.N Engl J Med. 2019;380(26):2518-2528.
-
OFEV® Local Summary of Product Characteristics, July 2024.