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 (RSV) Infection of the Lower Respiratory Tract.
- Marty FM Division of Infectious Disease, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
- Chemaly RF Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
- Mullane KM Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois, USA.
- Lee DG Department of Infectious Disease, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- Hirsch HH Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
- Small CB Department of Medicine/Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
- Bergeron A Service de pneumologie, Univ Paris Diderot, Hôpital Saint Louis, Paris, France.
- Shoham S Department of Medicine, Division of Infectious Diseases, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
- Ljungman P Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
- Waghmare A Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Blanchard E Department of Respiratory Diseases, CHU de Bordeaux, Bordeaux, France.
- Kim YJ Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
- McKevitt M Gilead Sciences, Inc., Foster City, California, USA.
- Porter DP Gilead Sciences, Inc., Foster City, California, USA.
- Jordan R Gilead Sciences, Inc., Foster City, California, USA.
- Guo Y Gilead Sciences, Inc., Foster City, California, USA.
- German P Gilead Sciences, Inc., Foster City, California, USA.
- Boeckh M Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
- Watkins TR Gilead Sciences, Inc., Foster City, California, USA.
- Chien JW Gilead Sciences, Inc., Foster City, California, USA.
- Dadwal SS Division of Infectious Disease, City of Hope National Medical Center, Duarte, California, USA.
- 2020-01-10
Published in:
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - 2019
Presatovir
hematopoietic cell transplant
lower respiratory tract infection
respiratory syncytial virus
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/cid/ciz1167
- PMID 31915807
- Persistent URL
- https://sonar.rero.ch/global/documents/11392
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