1. 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
- Author
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Marty, Francisco M, Chemaly, Roy F, Mullane, Kathleen M, Lee, Dong-Gun, Hirsch, Hans H, Small, Catherine B, Bergeron, Anne, Shoham, Shmuel, Ljungman, Per, Waghmare, Alpana, Blanchard, Elodie, Kim, Yae-Jean, McKevitt, Matt, Porter, Danielle P, Jordan, Robert, Guo, Ying, German, Polina, Boeckh, Michael, Watkins, Timothy R, and Chien, Jason W
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ANTIVIRAL agents , *CONFIDENCE intervals , *HEMATOPOIETIC stem cell transplantation , *MEDICAL cooperation , *PATIENT safety , *RESEARCH , *RESPIRATORY infections , *TRANSPLANTATION of organs, tissues, etc. , *RANDOMIZED controlled trials , *TREATMENT effectiveness , *BLIND experiment , *DATA analysis software , *DESCRIPTIVE statistics , *RESPIRATORY syncytial virus infections , *PHARMACODYNAMICS - 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. Clinical Trials Registration www.clinicaltrials.gov , NCT02254421; EudraCT, #2014-002475-29 [ABSTRACT FROM AUTHOR]
- Published
- 2020
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