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Publications

Journal Article Ahead of print

PubMed: 42085224 DOI: 10.1093/ajrccm/aamag155

Deupirfenidone Compared with Pirfenidone and Placebo in Idiopathic Pulmonary Fibrosis (ELEVATE-IPF): a Phase 2b Randomized Placebo-Controlled Trial.

Am J Respir Crit Care Med

Authors: Toby M Maher, Mark J Hamblin, Won-Ii Choi, Amy Hajari Case, Ioannis P Tomos, Argyrios E Tzouvelekis, Jessica E Shore, Miguel A Bergna, David Golod, Eric Elenko, Yanqiong Zhang, Camilla S Graham, Jin Woo Song, Tejaswini Kulkarni

Affiliations

  • National Heart and Lung Institute, Imperial College, London, United Kingdom and Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
  • Internal Medicine, University of Kansas Medical Center, Kansas City, KS, United States.
  • Dept. of Internal Medicine, Hanyang University, Myongji Hospital, Goyang-si, Republic of Korea.
  • Pulmonary, Critical Care, and Sleep, Piedmont Healthcare, Atlanta, GA, United States.
  • 5th Pulmonary Medicine Department, SOTIRIA Chest Diseases Hospital of Athens, Athens, Greece.
  • Department of Respiratory Medicine, University of Patras, PATRAS, Greece.
  • Pulmonary Fibrosis Foundation, Chicago, IL, United States.
  • Research, CEMER, FL, Vicente López, Argentina.
  • PureTech Health, Boston, MA, United States.
  • Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.

Abstract

RATIONALE

Deupirfenidone is a strategically deuterated form of pirfenidone that retains pharmacodynamic activity but has a differentiated pharmacokinetic profile that may enable improved efficacy and favorable tolerability in patients with idiopathic pulmonary fibrosis (IPF).

OBJECTIVE

To evaluate the efficacy and safety of deupirfenidone compared with placebo and pirfenidone in patients with IPF.

METHODS

Patients were randomized 1:1:1:1 to deupirfenidone 550 mg TID, deupirfenidone 825 mg TID, pirfenidone 801 mg TID or placebo. The primary endpoint was the rate of change in forced vital capacity (FVC) for the combined arms of deupirfenidone versus placebo at 26 weeks. The primary and secondary analyses used Bayesian and frequentist approaches, respectively.

MEASUREMENTS AND MAIN RESULTS

257 patients with IPF were randomized and the proportion on treatment at end of study was 80.0%, 68.3%, 64.6%, and 78.1% for the placebo, pirfenidone, deupirfenidone 550 mg, and deupirfenidone 825 mg arms, respectively. Posterior mean change in FVC for placebo was -110.71 mL (95% credible interval (CI), -148.75, -70.98) and for the combined deupirfenidone arms was -48.42 mL (95% CI, -87.66, -9.04) with a posterior mean difference of 62.29 mL (95% CI l, -6.13, 115.73; posterior probability, 0.985). Using a frequentist approach, the adjusted mean change in FVC for the placebo arm was -112.5 mL (95% CI, -167.2, -57.8) and for the deupirfenidone 825 mg arm was -21.5 mL (95% CI, -78.2, 35.1); the adjusted mean difference was 91.0 mL (95% CI, 12.2, 169.7; P = .02). The most common adverse events for each active treatment arm were gastrointestinal.

CONCLUSIONS

In patients with IPF, treatment with deupirfenidone slowed lung disease progression over 26 weeks.

TRIAL REGISTRATION

Clinicaltrials.gov number NCT05321420.

MeSH

Idiopathic Pulmonary Fibrosis, Fibrosis, Critical Care, Pulmonary Fibrosis, Therapeutics, Vital Capacity