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Clin Infect Dis. 2019 Dec 3. pii: ciz1166. doi: 10.1093/cid/ciz1166. [Epub ahead of print]

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.

Author information

1
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston TX, USA.
2
Division of Infectious Disease, City of Hope National Medical Center, Duarte, CA, USA.
3
Service de pneumologie, Univ 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, WA, USA.
7
Department of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA, USA.
8
Department of Respiratory Diseases, CHU de Bordeaux, Bordeaux, France.
9
Department of Medicine, UCLA Ronald Reagan Medical Center, Los Angeles, CA, USA.
10
Department of Hematology/Oncology, Loyola University Medical Center, Chicago, IL, 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, Israel.
14
Department of Medicine/Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA.
15
Section of Infectious Diseases, University of Chicago Medical Center, Chicago, IL, USA.
16
Department of Infectious Diseases, Mayo Clinic Arizona, Phoenix/Scottsdale, AZ, 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, CA, USA.
20
Department of Infectious Disease, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA.

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/µL) 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 α = 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.

KEYWORDS:

hematopoietic cell transplant; presatovir; respiratory syncytial virus

PMID:
31793991
DOI:
10.1093/cid/ciz1166

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