Skip to main content
Full Prescribing Information Opens in new tab
  • Full Prescribing Information Opens in new tab

    • INBUILD® was a phase 3 trial that grouped chronic fibrosing ILDs with a progressive phenotype together based on clinical and biological similarities1

    INBUILD® WAS A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 TRIAL OVER 52 WEEKS IN PATIENTS WITH CHRONIC FIBROSING ILDs WITH A PROGRESSIVE PHENOTYPE2*

    INBUILD - Chronic Fibrosing ILD
    INBUILD - Chronic Fibrosing ILD

    * A range of ILDs, including autoimmune ILDs, with a progressive phenotype were included in INBUILD®: HP, 26.1% (n=173); iNSIP, 18.9% (n=125); unclassifiable IIP, 17.2% (n=114); other ILDs including sarcoidosis and exposure-related ILDs, 12.2% (n=81); autoimmune ILDs, 25.6% (n=170). Specific autoimmune ILDs included in INBUILD®: RA-ILD, 13.4% (n=89); SSc-ILD, 5.9% (n=39); mixed connective tissue disease-associated ILD, 2.9% (n=19); other autoimmune ILDs, 3.5% (n=23).3

    † Primary endpoint was assessed at 52 weeks.2

    Part B: Variable treatment period beyond Week 52 during which patients continued blinded treatment until all patients had completed Part A.3

    Primary endpoint2

    • Annual rate of decline in FVC over 52 weeks (measured in mL/year)

    INBUILD® recruited a range of patients with chronic fibrosing ILDs with clinical signs of progression3

    Key inclusion criteria3

    • Physician-diagnosed chronic fibrosing ILD, excluding IPF, with relevant fibrosis
    • Age ≥18 years (no upper limit)
    • >10% extent of fibrosis on HRCT
    • FVC ≥45% predicted value
    • DLCO 30%–<80% of predicted value
    • Met at least one of the following criteria for ILD progression within 24 months before screening, despite standard treatment‡:

      • Relative FVC decline of ≥10% predicted
      • Relative FVC decline of 5%–<10% predicted and worsening respiratory symptoms, or increased extent of fibrosis on HRCT
      • Worsening respiratory symptoms and an increased extent of fibrosis on HRCT

    Exclusion criteria2

    • Physician-diagnosed IPF
    • Relevant airways obstruction (ie, pre-bronchodilator FEV1/FVC <0.7)
    • Significant pulmonary hypertension
    • Had >1.5 times ULN of ALT, AST, or bilirubin
    • Known risk or predisposition to bleeding
    • Patients receiving a full dose of anticoagulation treatment
    • Recent history of myocardial infarction or stroke

    Patients were also excluded if they received other investigational therapy, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids >20 mg/day, or the combination of oral corticosteroids + azathioprine + n-acetylcysteine within 4 weeks of randomization, cyclophosphamide within 8 weeks prior to randomization, or rituximab within 6 months, or previous treatment with nintedanib or pirfenidone.

    ‡ Patients taking nintedanib or pirfenidone were excluded.2

    A total of 663 patients underwent randomization3

    Key demographic and baseline characteristics

    Demographics

     OFEV (n=332)Placebo (n=331)
    Male sex, %53.953.5
    Age–years, (SD)65.2 (9.7)66.3 (9.8)
    Former or current smoker, %50.951.1

    Lung function

     OFEV (n=332)Placebo (n=331)
    Mean FVC, mL2340 (740)2321 (728)
    Mean FVC, % predicted (SD)68.7 (16)69.3 (15.2)
    Mean DLCO, % mL§3.5 (1.2)3.7 (1.3)
    Mean DLCO, % predicted (SD)§44.4 (11.9)47.9 (15)

    Diagnostic criteria (previous 24 months)

     OFEV (n=332)Placebo (n=331)
    UIP-like fibrotic pattern on HRCT, %6262.2
    Other fibrotic pattern on HRCT, %3837.8

    Progression criteria (previous 24 months)

     OFEV (n=332)Placebo (n=331)

    Relative decline in FVC of ≥10% of 

    predicted value, %

    		48.252

    Relative decline in FVC of 5% to 

    <10% of predicted value plus 

    worsening of respiratory symptoms 

    or increased extent of fibrosis 

    on HRCT, %

    		33.129.3

    Worsening of respiratory symptoms

    and increased extent of fibrosis on 

    HRCT, %

    		18.718.4

    § The values for DLCO were corrected for the hemoglobin level.

    THERE WERE 2 COPRIMARY POPULATIONS IN INBUILD®2,3||

    • Overall population
    • Patients with a UIP-like HRCT pattern

    UIP-LIKE AND OTHER FIBROTIC PATTERNS WERE INCLUDED IN INBUILD®3¶

    All patients enrolled in INBUILD® were required to have reticular abnormality with traction bronchiectasis, with or without honeycombing, with disease extent of >10% on HRCT. INBUILD® also included the following HRCT features:

    • Ground glass opacity
    • Centrilobular nodules
    • Mosaic attenuation
    • Air trapping
    • Upper lung or peribronchovascular predominance

    UIP-like HRCT pattern3

    The co-population of patients with UIP-like HRCT features were required to have one of the following combinations of radiological criteria to be classified as UIP-like: A+B+C, A+C, or B+C

    Ico PlaceholderA
    Definite honeycomb lung destruction with basal and peripheral predominance
    Ico Placeholder B
    Presence of reticular abnormality and traction bronchiectasis consistent with fibrosis with basal and peripheral predominance
    Ico Placeholder (2)
    The absence of atypical features, specifically nodules and consolidation. Ground-glass opacity, if present, should be less extensive than reticular opacity pattern

    || Patients with other HRCT patterns represented the “complementary” population.4

    Widespread consolidation and progressive massive fibrosis on HRCT were not allowed in INBUILD®.4

    Other Fibrotic Patterns3

    HRCT scans that did not meet the UIP-like pattern criteria were classified as other fibrotic patterns.

    OFEV is proven to reduce lung function decline2

    OFEV (nintedanib) SIGNIFICANTLY REDUCED THE ANNUAL RATE OF DECLINE IN FVC BY 57% IN PATIENTS WITH CHRONIC FIBROSING ILDs WITH A PROGRESSIVE PHENOTYPE VS PLACEBO2#

    INBUILD
    INBUILD

    # The annual rate of decline in FVC (mL/year) was analyzed using a random coefficient regression model.2

    OFEV reduced the annual rate of decline in FVC in patients with and without a UIP-like HRCT pattern vs placebo2

    HRCT
    HRCT

    # The annual rate of decline in FVC (mL/year) was analyzed using a random coefficient regression model.2

    ** Comparison based on the other HRCT subpopulation was not included in the multiple testing procedure. Values shown are for descriptive purposes.2

    The safety profile of OFEV has been demonstrated in a clinical trial with 663 patients with chronic fibrosing ILDs with a progressive phenotype2

    Adverse reactions reported in ≥5% of OFEV (nintedanib)-treated patients and more commonly than placebo4

     OFEV (n=322)Placebo (n=331)
    Diarrhea367%24%
    Nausea329%9%
    Liver enzyme elevation4††23%6%
    Abdominal pain4‡‡18%5%
    Vomiting318%5%
    Decreased appetite315%5%
    Nasopharyngitis213%12%
    Weight decreased312%3%
    Headache311%7%
    Fatigue210%6%
    Upper respiratory tract infection27%6%
    Urinary tract infection26%4%
    Back pain26%5%
    • 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)4
    • The safety profile in patients with chronic fibrosing ILDs with a progressive phenotype treated with OFEV was consistent with that observed in IPF patients2

    †† Includes alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, and blood alkaline phosphatase increased.4

    ‡‡ Includes abdominal pain, abdominal pain upper, and abdominal pain lower.4

    Dose reduction, treatment interruption, and discontinuation were used to manage adverse reactions2

    THE MOST COMMON ADVERSE REACTIONS WERE GASTROINTESTINAL IN NATURE AND GENERALLY OF MILD OR MODERATE INTENSITY2

    intensity
    The majority of diarrhea events in patients taking OFEV were of mild or moderate intensity2
    months
    The majority of diarrhea events occurred within the first 3 months of treatment2
    6%patient
    6% of all patients studied discontinued treatment due to diarrhea events vs <1% of placebo-treated patients2

    ALT, alanine aminotransferase; AST, aspartate aminotransferase; DLCO, diffusing capacity of the lungs for carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HP, hypersensitivity pneumonitis; HRCT, high-resolution computed tomography; IIP, idiopathic interstitial pneumonia; ILD, interstitial lung disease; iNSIP, idiopathic nonspecific interstitial pneumonia; IPF, idiopathic pulmonary fibrosis; RA, rheumatoid arthritis; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; SD, standard deviation; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease; UIP, usual interstitial pneumonia; ULN, upper limit of normal.

    References

    1. Flaherty KR, et al. BMJ Open Respir Res. 2017;4(1):e000212.

    2. 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.

    3. Flaherty KR, et al. N Engl J Med. 2019;381(18):1718-1727.

    4. OFEV® Local Summary of Product Characteristics, July 2024.