TABLE 2

Ongoing clinical trials of antifibrotic medications in non-idiopathic pulmonary fibrosis (IPF) fibrotic interstitial lung diseases (ILDs)

NamePhasePatientsInterventionDurationPrimary outcomeKey secondary outcomes
Nintedanib
NCT02597933 [91]Safety and Efficacy of 150 mg Nintedanib Twice Daily in Systemic Sclerosis (SENSCIS)IIIn=580, SSc-pulmonary fibrosisNintedanib 150 mg twice daily or placebo added to exisiting treatment (stable dose methotrexate, MMF and/or prednisone ≤10 mg daily)52 weeksAnnual rate of decline FVC (mL)Time to all-cause mortality, absolute change dyspnoea score, Modified Rodan Skin Score, SGRQ, change in FVC % pred, change DLCO
NCT02999178 [92]Efficacy and Safety of Nintedanib in Patients with Progressive Fibrosing-ILD (INBUILD®)IIIn=663, progressive fibrosing ILD (see text)Nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVCChange in K-BILD score, time to first AE or death, time to progression (≥10% decrease FVC or death)
NCT03283007 [93]Nintedanib in Lung Transplant Recipients with BOS Grade 1–2 (INFINITx-BOS)IIIn=80, ≥6 months post-lung transplant with BOSNintedanib 150 mg twice daily or placebo (patients already on azithromycin)6 monthsRate of decline in FEV1 (mL) over 6 monthsChange 6MWD, change SGRQ, change in BOS grade, absolute change oxygen saturation
Pirfenidone
NCT02821689 [94]Pirfenidone in Progressive ILD Associated with Clinically Amyopathic DermatomyositisIVn=60, CADM with ILD1800 mg pirfenidone total per day or placebo added on to existing treatment52 weeksOverall survivalChange in HRCT score, change in PFT from baseline
NCT03221257 [95]Scleroderma Lung Study III – Combining Pirfenidone with Mycophenolate (SLSIII)IIn=150, SSc-pulmonary fibrosisPirfenidone (target dose 801 mg three times daily) or placebo+MMF (target dose of 1500 mg twice daily)18 monthsChange in FVC % predChange DLCO % pred, change modified Rodan Skin Score, SGRQ, dyspnoea assessment score, change from baseline ILD by computer-quantified HRCT
 DRKS00009822 [96]Exploring Efficacy and Safety of Pirfenidone for Progressive, Non-IPF Lung Fibrosis (RELIEF)IICollagen vascular disease-associated fibrosis, fibrotic NSIP, cHP, asbestos-related lung fibrosisPirfenidone (801 mg three times daily) or placebo48 weeksAbsolute change in FVC (%) from baseline to week 48Time to disease worsening, change in DLCO, 6MWD, SGRQ and EQ-5D
NCT03099187 [97]A Study of Pirfenidone in Patients with Unclassifiable Progressive Fibrosing Interstitial Lung DiseaseIIn=252, nonclassifiable ILD (cannot be classified to a specific category of ILD with moderate or high level of confidence with MDD)Pirfenidone (801 mg three times daily) or placebo (stable dose MMF allowed)24 weeksRate of decline in FVC over 24 weeksChange in FVC (% pred), change in DLCO (% pred), change in FVC of >5%, change in FVC of >10%, change in 6MWD, change in symptom scores (dyspnoea, cough), SGRQ score, AE-IPF, PFS
NCT03385668 [98]Pilot Study of Pirfenidone in Pulmonary Fibrosis with Anti-myeloperoxidase Antibodies (PIRFENIVAS)II15 patients with+anti-MPO antibody and pulmonary fibrosis (definite or possible UIP or NSIP on HRCT)Pirfenidone (2403 mg total daily dose) (no placebo group)52 weeksAbsolute change FVC % predTreatment emergent adverse events, change FVC % pred, 6MWD, change % DLCO, PFS
NCT02808871 [99]Phase II Study of Pirfenidone in Patients with RA-ILD (TRAIL1)II270 patients with RA-ILDPirfenidone 801 mg three times daily or placebo52 weeksComposite end-point: ≥10% decline in FVC or deathRelative decline DLCO (≥15%), relative decline in FVC (≥10%), acute exacerbation, dyspnoea scores, SGRQ
NCT03260556 [100]Pirfenidone for Progressive Fibrotic Sarcoidosis (PirFS)IV60 patients with sarcoidosis and >20% fibrosis on HRCT (stable immunosuppressive medications and/or ≤ 20 mg prednisone/day for 2 months prior allowed)Pirfenidone 801 mg three times daily or placebo24 monthsTime until clinical worseningChange in FVC, change in composite physiologic index
NCT02958917 [90]Study of Efficacy and Safety of Pirfenidone in Patients with Fibrotic Hypersensitivity PneumonitisN/A40 patients with fibrotic hypersensitivity pneumonitisPirfenidone 801 mg three times daily or placebo52 weeksMean change in FVCPFS, ≥5% mean change FVC, acute exacerbation, 6MWD
NCT02496182 [89]Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment (Picheon)II/IIIn=60, cHPPirfenidone (1800 mg or 1200 mg total daily dose) or placebo in addition to conventional therapy (prednisone and azathioprine)52 weeksChange in FVCInflammation and fibrosis grade on HRCT (Kazerooni scale), 6MWD, SGRQ score
NCT02262299 [101]European Trial of Pirfenidone in BOS, A European Multi-center Study (EPOS)II/IIIn=80, ≥6 months post-lung transplant with grade 1–3 BOSPirfenidone 801 mg three times daily or placebo (patients already on azithromycin)26 weeksChange in FEV1 (in L) over 26 weeks% change in FEV1, % change FVC, change in % pred DLCO, change 6MWD, change BOS grade, hospitalisation, survival

SSc: systemic sclerosis; MMF: mycophenolate mofetil; FVC: forced vital capacity; SGRQ: St George's Respiratory Questionnaire; % pred: % predicted; DLCO: diffusing capacity of the lung for carbon monoxide; K-BILD: King's Brief Interstitial Lung Disease questionnaire; AE: adverse event; BOS: bronchiolitis obliterans syndrome; FEV1: forced expiratory volume in 1 s; 6MWD: 6-min walk distance; CADM: clinically amyopathic dermatomyositis; HRCT: high-resolution computed tomography; PFT: pulmonary function test; NSIP: nonspecific interstitial pneumonia; cHP: chronic hypersensitivity pneumonitis; EQ-5D: EuroQuol five-dimensions questionnaire; MDD: multidisciplinary discussion; MPO: myeloperoxidase; UIP: usual interstitial pneumonia; PFS: progression-free survival; RA: rheumatoid arthritis.