A phase 2, randomized, double-blind, placebo-controlled trial of presatovir for the treatment of respiratory syncytial virus upper respiratory tract infection in hematopoietic-cell transplant recipients. Journal Article


Authors: Chemaly, RF; Dadwal, SS; Bergeron, A; Ljungman, P; Kim, YJ; Cheng, GS; Pipavath, SN; Limaye, AP; Blanchard, E; Winston, DJ; Stiff, PJ; Zuckerman, T; Lachance, S; Rahav, G; Small, CB; Mullane, KM; Patron, RL; Lee, DG; Hirsch, HH; Waghmare, A; McKevitt, M; Jordan, R; Guo, Y; German, P; Porter, DP; Gossage, DL; Watkins, TR; Marty, FM; Chien, JW; Boeckh, M
Article Title: A phase 2, randomized, double-blind, placebo-controlled trial of presatovir for the treatment of respiratory syncytial virus upper respiratory tract infection in hematopoietic-cell transplant recipients.
Abstract: BACKGROUND: Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind phase 2 trial in HCT recipients with RSV upper respiratory tract infection (URTI). METHODS: Patients were randomized, stratified by lymphopenia (200/┬ÁL) and ribavirin use, to receive oral presatovir 200 mg or placebo on days 1, 5, 9, 13, and 17, and followed through day 28. The coprimary efficacy endpoints were time-weighted average change in nasal RSV viral load between days 1 and 9, and proportion of patients developing lower respiratory tract complications (LRTC) through day 28. RESULTS: From January 23, 2015, to June 16, 2017, 189 patients were randomized (96 presatovir, 93 placebo). Presatovir vs placebo treatment did not significantly affect (prespecified a = 0.01) time-weighted average decline in RSV viral load from day 1 to 9 (treatment difference: -0.33 log10 copies/mL; 95% CI: -0.64, -0.02 log10 copies/mL; p = 0.040) or progression to LRTC (11.2% vs 19.5%; odds ratio [95% CI], 0.50 [0.22, 1.18]; p = 0.11). In post hoc analysis among patients with lymphopenia, presatovir vs placebo treatment decreased LRTC development by day 28 (2/15 [13.3%] vs 9/14 [64.3%], p = 0.008). Adverse events were similar for patients receiving presatovir vs placebo. CONCLUSIONS: Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia.
Journal Title: Clinical Infectious Diseases
ISSN: 1058-4838
Publisher: Unknown  
Date Published: 2019