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
Year: 2019
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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 II trial in HCT recipients with RSV upper respiratory tract infections. METHODS: Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. RESULTS: From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, -0.33 log10 copies/mL; 95% confidence interval [CI] -.64 to -.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22-1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the 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. CLINICAL TRIALS REGISTRATION: NCT02254408; EUDRA-CT#2014-002474-36.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciz1166
Authors: Roy F Chemaly, Sanjeet S Dadwal, Anne Bergeron, Per Ljungman, Yae-Jean Kim, Guang-Shing Cheng, Sudhakar N Pipavath, Ajit P Limaye, Elodie Blanchard, Drew J Winston, Patrick J Stiff, Tsila Zuckerman, Silvy Lachance, Galia Rahav, Catherine B Small, Kathleen M Mullane, Roberto L Patron, Dong-Gun Lee, Hans H Hirsch, Alpana Waghmare, Matt McKevitt, Robert Jordan, Ying Guo, Polina German, Danielle P Porter, David L Gossage, Timothy R Watkins, Francisco M Marty, Jason W Chien, Michael Boeckh
Institutions: The University of Texas MD Anderson Cancer Center, City Of Hope National Medical Center, Hôpital Saint-Louis, Université Paris Diderot, Karolinska University Hospital, Karolinska Institutet, Samsung Medical Center, Sungkyunkwan University, University of Washington, Fred Hutch Cancer Center, Centre Hospitalier Universitaire de Bordeaux, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, Loyola University Medical Center, Loyola University Chicago, Rambam Health Care Campus, Hôpital Maisonneuve-Rosemont, Université de Montréal, Tel Aviv University, Sheba Medical Center, Weill Cornell Medicine, University of Chicago Medical Center, Mayo Clinic in Arizona, Mayo Clinic Hospital, Catholic University of Korea, University Hospital of Basel, Gilead Sciences (United States), Brigham and Women's Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Awards: G111615301, G876475942
OpenAlex ID: W2991708524