scholarly journals Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD)

2021 ◽  
Vol 8 (1) ◽  
pp. e001026
Author(s):  
Tamera J Corte ◽  
Lisa Lancaster ◽  
Jeffrey J Swigris ◽  
Toby M Maher ◽  
Jonathan G Goldin ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Treatment Period ◽  
Lysophosphatidic Acid ◽  
Good Clinical Practice ◽  
Rate Of Change ◽  
Phase 2 ◽  
Double Blind ◽  
Controlled Treatment ◽  
Fibrotic Diseases

IntroductionIdiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA1–6). Signalling via LPA1 appears to be fundamental in the pathogenesis of fibrotic diseases. BMS-986278, a second-generation LPA1 antagonist, is currently in phase 2 development as a therapy for IPF and PF-ILD.Methods and analysisThis phase 2, randomised, double-blind, placebo-controlled, parallel-group, international trial will include adults with IPF or PF-ILD. The trial will consist of a 42-day screening period, a 26-week placebo-controlled treatment period, an optional 26-week active-treatment extension period, and a 28-day post-treatment follow-up. Patients in both the IPF (n=240) and PF-ILD (n=120) cohorts will be randomised 1:1:1 to receive 30 mg or 60 mg BMS-986278, or placebo, administered orally two times per day for 26 weeks in the placebo-controlled treatment period. The primary endpoint is rate of change in per cent predicted forced vital capacity from baseline to week 26 in the IPF cohort.Ethics and disseminationThis study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.Trial registration numberNCT04308681.

Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial

2017 ◽  
Vol 5 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Ganesh Raghu ◽  
Kevin K Brown ◽  
Harold R Collard ◽  
Vincent Cottin ◽  
Kevin F Gibson ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Trial

scholarly journals Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis

2020 ◽  
pp. 1902442
Author(s):  
Toby M. Maher ◽  
Ulrich Costabel ◽  
Marilyn K. Glassberg ◽  
Yasuhiro Kondoh ◽  
Takashi Ogura ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Primary Endpoint ◽  
Safety Profile ◽  
Controlled Trial ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Treatment Naïve ◽  
To Receive

This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ≥40 years with % predicted forced vital capacity (%FVC) 40%–100% and diffusing capacity for carbon monoxide 25%–90% and who were treatment-naive (Cohort A) or receiving pirfenidone (2403 mg·day−1; Cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of %FVC decline over 52 weeks.In Cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In Cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of %FVC decline) was not met in Cohort A (lebrikizumab versus placebo, −5.2% versus −6.2%; p=0.456) or Cohort B (lebrikizumab versus placebo, −5.5% versus −6.0%; p=0.557). In Cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio, 0.42 [95% CI, 0.17–1.04]). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced %FVC decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.

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