TABLE 2.
Ongoing clinical trials of antifibrotic medications in non-idiopathic pulmonary fibrosis (IPF) fibrotic interstitial lung diseases (ILDs)
| Name | Phase | Patients | Intervention | Duration | Primary outcome | Key secondary outcomes | |
| Nintedanib | |||||||
| NCT02597933 [91] | Safety and Efficacy of 150 mg Nintedanib Twice Daily in Systemic Sclerosis (SENSCIS) | III | n=580, SSc-pulmonary fibrosis | Nintedanib 150 mg twice daily or placebo added to exisiting treatment (stable dose methotrexate, MMF and/or prednisone ≤10 mg daily) | 52 weeks | Annual 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®) | III | n=663, progressive fibrosing ILD (see text) | Nintedanib 150 mg twice daily or placebo | 52 weeks | Annual rate of decline FVC | Change 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) | III | n=80, ≥6 months post-lung transplant with BOS | Nintedanib 150 mg twice daily or placebo (patients already on azithromycin) | 6 months | Rate of decline in FEV1 (mL) over 6 months | Change 6MWD, change SGRQ, change in BOS grade, absolute change oxygen saturation |
| Pirfenidone | |||||||
| NCT02821689 [94] | Pirfenidone in Progressive ILD Associated with Clinically Amyopathic Dermatomyositis | IV | n=60, CADM with ILD | 1800 mg pirfenidone total per day or placebo added on to existing treatment | 52 weeks | Overall survival | Change in HRCT score, change in PFT from baseline |
| NCT03221257 [95] | Scleroderma Lung Study III – Combining Pirfenidone with Mycophenolate (SLSIII) | II | n=150, SSc-pulmonary fibrosis | Pirfenidone (target dose 801 mg three times daily) or placebo+MMF (target dose of 1500 mg twice daily) | 18 months | Change in FVC % pred | Change 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) | II | Collagen vascular disease-associated fibrosis, fibrotic NSIP, cHP, asbestos-related lung fibrosis | Pirfenidone (801 mg three times daily) or placebo | 48 weeks | Absolute change in FVC (%) from baseline to week 48 | Time 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 Disease | II | n=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 weeks | Rate of decline in FVC over 24 weeks | Change 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) | II | 15 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 weeks | Absolute change FVC % pred | Treatment emergent adverse events, change FVC % pred, 6MWD, change % DLCO, PFS |
| NCT02808871 [99] | Phase II Study of Pirfenidone in Patients with RA-ILD (TRAIL1) | II | 270 patients with RA-ILD | Pirfenidone 801 mg three times daily or placebo | 52 weeks | Composite end-point: ≥10% decline in FVC or death | Relative decline DLCO (≥15%), relative decline in FVC (≥10%), acute exacerbation, dyspnoea scores, SGRQ |
| NCT03260556 [100] | Pirfenidone for Progressive Fibrotic Sarcoidosis (PirFS) | IV | 60 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 placebo | 24 months | Time until clinical worsening | Change in FVC, change in composite physiologic index |
| NCT02958917 [90] | Study of Efficacy and Safety of Pirfenidone in Patients with Fibrotic Hypersensitivity Pneumonitis | N/A | 40 patients with fibrotic hypersensitivity pneumonitis | Pirfenidone 801 mg three times daily or placebo | 52 weeks | Mean change in FVC | PFS, ≥5% mean change FVC, acute exacerbation, 6MWD |
| NCT02496182 [89] | Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment (Picheon) | II/III | n=60, cHP | Pirfenidone (1800 mg or 1200 mg total daily dose) or placebo in addition to conventional therapy (prednisone and azathioprine) | 52 weeks | Change in FVC | Inflammation 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/III | n=80, ≥6 months post-lung transplant with grade 1–3 BOS | Pirfenidone 801 mg three times daily or placebo (patients already on azithromycin) | 26 weeks | Change 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.