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-Reference-Cited by-同舟云学术

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

Published:2019-12-03 Issue:11 Volume:71 Page:2777-2786
ISSN:1058-4838
Container-title:Clinical Infectious Diseases
language:en
Short-container-title:

Author:

Chemaly Roy F¹,Dadwal Sanjeet S²,Bergeron Anne³,Ljungman Per⁴,Kim Yae-Jean⁵,Cheng Guang-Shing⁶⁷,Pipavath Sudhakar N⁷,Limaye Ajit P⁷,Blanchard Elodie⁸,Winston Drew J⁹,Stiff Patrick J¹⁰,Zuckerman Tsila¹¹,Lachance Silvy¹²,Rahav Galia¹³,Small Catherine B¹⁴,Mullane Kathleen M¹⁵,Patron Roberto L¹⁶,Lee Dong-Gun¹⁷,Hirsch Hans H¹⁸,Waghmare Alpana⁶⁷,McKevitt Matt¹⁹,Jordan Robert¹⁹,Guo Ying¹⁹,German Polina¹⁹,Porter Danielle P¹⁹,Gossage David L¹⁹,Watkins Timothy R¹⁹,Marty Francisco M²⁰,Chien Jason W¹⁹,Boeckh Michael⁶⁷

Affiliation:

1. Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2. Division of Infectious Disease, City of Hope National Medical Center, Duarte, California, USA

3. Service de Pneumologie, Université Paris Diderot, Hôpital Saint Louis, Paris, France

4. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

5. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

6. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

7. Department of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington, USA

8. Department of Respiratory Diseases, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

9. Department of Medicine, University of California Los Angeles Ronald Reagan Medical Center, Los Angeles, California, USA

10. Department of Hematology/Oncology, Loyola University Medical Center, Chicago, Illinois, USA

11. Hematology Institute, Rambam Medical Health Care Campus, Haifa, Israel

12. Hematology-Oncology Department, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Québec, Canada

13. Infectious Diseases Unit, Chaim Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel

14. Department of Medicine/Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA

15. Section of Infectious Diseases, University of Chicago Medical Center, Chicago, Illinois, USA

16. Department of Infectious Diseases, Mayo Clinic Arizona, Phoenix, Arizona, USA

17. Department of Infectious Disease, College of Medicine, The Catholic University of Korea, Seoul, South Korea

18. Department of Biomedicine, University Hospital Basel, Basel, Switzerland

19. Gilead Sciences Inc., Foster City, California, USA

20. Department of Infectious Disease, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts, USA

Abstract

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.

Funder

Gilead Sciences Inc

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Link

http://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciz1166/31773236/ciz1166.pdf

Reference30 articles.

1. Respiratory syncytial virus infection in patients with hematological diseases: single-center study and review of the literature;Khanna;Clin Infect Dis,2008

2. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies;Martino;Biol Blood Marrow Transplant,2005

3. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience;Nichols;Biol Blood Marrow Transplant,2001