A phase 2b, randomized, double-blind, placebo-controlled multicenter study evaluating antiviral effects, pharmacokinetics, safety, and tolerability of presatovir in hematopoietic cell transplant recipients with respiratory syncytial virus infection of the lower respiratory tract

Francisco M. Marty, Roy F. Chemaly, Kathleen M. Mullane, Dong Gun Lee, Hans H. Hirsch, Catherine B. Small, Anne Bergeron, Shmuel Shoham, Per Ljungman, Alpana Waghmare, Elodie Blanchard, Yae Jean Kim, Matt McKevitt, Danielle P. Porter, Robert Jordan, Ying Guo, Polina German, Michael Boeckh, Timothy R. Watkins, Jason W. ChienSanjeet S. Dadwal

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Presatovir significantly reduced nasal viral load, signs, and symptoms of respiratory syncytial virus (RSV) infection in a human challenge study. We evaluated presatovir in hematopoietic-cell transplant (HCT) recipients with RSV lower respiratory tract infection (LRTI). Methods. Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. The primary endpoint was time-weighted average change in nasal RSV viral load through day 9. Secondary endpoints included supplemental oxygen-free days, incident respiratory failure requiring mechanical ventilation, and all-cause mortality. Results. From January 31, 2015, to March 20, 2017, 60 patients from 17 centers were randomized (31 presatovir, 29 placebo); 59 received study treatment (50 allogeneic, 9 autologous HCT). In the efficacy population (29 presatovir, 28 placebo), presatovir treatment did not significantly reduce time-weighted average change in viral load (−1.12 vs −1.09 log10 copies/mL; treatment difference −0.02 log10 copies/mL, 95% confidence interval: −.62,.57; P =.94), median supplemental oxygen-free days (26 vs 28 days, P =.84), incident respiratory failure (10.3 vs 10.7%, P =.98), or all-cause mortality (0 vs 7.1%, P =.19) versus placebo. Adverse events were similar between arms (presatovir 80%, placebo 79%). Resistance-associated substitutions in RSV fusion protein emerged in 6/29 presatovir-treated patients. Conclusions. Presatovir treatment was well tolerated in HCT patients with RSV LRTI but did not improve virologic or clinical outcomes versus placebo.

Original languageEnglish (US)
Pages (from-to)2787-2795
Number of pages9
JournalClinical Infectious Diseases
Volume71
Issue number11
DOIs
StatePublished - Dec 1 2020

Keywords

  • Hematopoietic cell transplant
  • Lower respiratory tract infection
  • Presatovir
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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