Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients With Respiratory Syncytial Virus (RSV) Infection of the Upper Respiratory Tract

The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV upper respiratory tract infection (URTI), the effect of presatovir on development of lower respiratory tract complication, being free of any supplemental oxygen progression to respiratory failure, and pharmacokinetics (PK), safety, and tolerability of presatovir.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Drug: Presatovir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia
    • Royal Brisbane & Women's Hospital
  • Melbourne, Australia
    • Royal Melbourne Hospital
  • New South Wales
    • Westmead, New South Wales, Australia
      • Westmead Hospital
• Brazil
  • Porto Alegre, Brazil
    • Hospital de Clínicas de Porto Alegre
  • Sao Paulo, Brazil
    • Hospital Israelita Albert Einstein
  • Sao Paulo, Brazil
    • Hospital Universitário USP
  • São Paulo, Brazil
    • Fundacao Faculdade Regional Medicina de Sao Jose do Rio Preto
  • São Paulo, Brazil
    • Fundação Antonio Prudente - Hospital do Câncer AC Camargo
  • São Paulo, Brazil
    • Hospital Santa Marcelina
  • São Paulo, Brazil
    • Instituto Brasileiro de Controle do Cancer-IBCC
• Canada
  • Calgary, Canada
    • Tom Baker Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada
      • Hôpital Maisonneuve-Rosemont
• France
  • Bordeaux, France
    • CHU de Bordeaux
  • Paris, France
    • Hopital Saint-Louis, APHP
  • Suresnes, France
    • Hopital Foch
  • Toulouse, France
    • Institut Universitaire du Cancer Oncopole
• Germany
  • Wurzburg, Germany
    • Universitatsklinikum Wurzburg
• Israel
  • Beer Sheva, Israel
    • Soroka Medical Center
  • Haifa, Israel
    • Rambam Medical Center
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Ramat Gan, Israel
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • Seoul Saint Mary's Hospital
• Netherlands
  • Amsterdam, Netherlands
    • VUmc cancer center
  • Rotterdam, Netherlands
    • Erasmus Medical Center (Rotterdam)
• Singapore
  • Singapore, Singapore
    • Singapore General Hospital
  • Singapore, Singapore
    • UMC National University Health System
• Spain
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio
• Sweden
  • Stockholm, Sweden
    • Karolinska Institutet
• Switzerland
  • Basel, Switzerland
    • University Clinic Basel
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taoyuan, Taiwan
    • Chang Gung Medical Foundation-Linkou Branch
• United Kingdom
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals Trust
  • London, United Kingdom
    • King's College Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Mayo Clinic Arizona
  • California
    • Duarte, California, United States
      • City of Hope
    • Los Angeles, California, United States
      • UCLA David Geffen School of Medicine
    • Stanford, California, United States
      • Stanford University
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University
    • Atlanta, Georgia, United States
      • Northside Medical Center
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern University
    • Chicago, Illinois, United States
      • University of Chicago
    • Maywood, Illinois, United States
      • Loyola University
  • Maryland
    • Baltimore, Maryland, United States
      • John Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States
      • University of Massachusetts Memorial Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan
    • Detroit, Michigan, United States
      • Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington University
  • New York
    • New York, New York, United States
      • Memorial Sloan Kettering
    • New York, New York, United States
      • New York Presbyterian Hospital Cornell Medical Center
  • North Carolina
    • Durham, North Carolina, United States
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States
      • University Hospital Case Medical
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health Sciences University
  • Tennessee
    • Nashville, Tennessee, United States
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States
      • Md Anderson Cancer Center
    • San Antonio, Texas, United States
      • Texas Transplant Institute (SCRI)
  • Utah
    • Salt Lake City, Utah, United States
      • University of Utah
  • Washington
    • Seattle, Washington, United States
      • Fred Hutchison Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Received an autologous or allogeneic HCT using any conditioning regimen
• Documented to be RSV-positive as determined by local testing (eg, polymerase chain reaction, direct fluorescence antibody, respiratory viral panel assay, or culture) using an upper respiratory tract sample collected ≤ 6 days prior to Day 1
• New onset of at least 1 of the following respiratory symptoms for ≤ 7 days prior to Day 1: nasal congestion, runny nose, cough, or sore throat, or worsening of one of these chronic (associated with a previously existing diagnosis, eg, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms ≤ 7 days prior to Day 1
• No evidence of new abnormalities consistent with lower respiratory tract infection (LRTI) on a chest X-ray relative to the most recent chest X-ray, as determined by the local radiologist. If a chest X-ray is not available or was not obtained during standard care < 48 hours prior to screening, a chest X-ray must be obtained for screening
• O2 saturation ≥ 92% on room air
• An informed consent document signed and dated by the participant or a legal guardian of the participant and the investigator or his/her designee
• A negative urine or serum pregnancy test is required for female participants (unless surgically sterile or greater than two years post-menopausal)
• Male and female participants of childbearing potential must agree to contraceptive requirements as described in the study protocol
• Willingness to complete necessary study procedures and have available a working telephone or email

Exclusion Criteria:

Related to concomitant or previous medication use:

• Use of non-marketed (according to region) investigational agents within 30 days, OR use of any monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT

Related to medical history:

• Pregnant, breastfeeding, or lactating females
• Unable to tolerate nasal sampling required for this study, as determined by the investigator
• Known history of HIV/AIDS with a CD4 count <200 cells/μL within the last month
• History of drug and/or alcohol abuse that, in the opinion of the investigator, may prevent adherence to study activities

Related to medical condition at screening:

• Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, or human metapneumovirus, or coronavirus) within 7 days prior to the screening visit, as determined by local testing (additional testing is not required)
• Clinically significant bacteremia or fungemia within 7 days prior to screening that has not been adequately treated, as determined by the investigator
• Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to screening that has not been adequately treated, as determined by the investigator
• Excessive nausea/vomiting at screening, as determined by the investigator, or an inability to swallow pills that precludes oral administration of the investigational medical product (for participants without an nasogastric tube in place)
• Any condition which, in the opinion of the investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints

Related to laboratory results:

• Creatinine clearance < 30 mL/min (calculated using the Cockcroft-Gault method)
• Clinically significant aspartate aminotransferase/alanine aminotransferase, as determined by the investigator
• Clinically significant total bilirubin, as determined by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Presatovir; Participants will receive presatovir on Days 1, 5, 9, 13, and 17, with follow-up visits through Day 28, and may continue in an optional extended monitoring phase with visits through Day 56.	Drug: Presatovir; Presatovir 200 mg (4 × 50 mg tablets) administered orally or via nasogastric (NG) tube; Other Names: GS-5806
Placebo Comparator: Placebo; Participants will receive placebo on Days 1, 5, 9, 13, and 17, with follow-up visits through Day 28, and may continue in an optional extended monitoring phase with visits through Day 56.	Drug: Placebo; Tablets administered orally or via nasogastric tube

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9	The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.	Baseline; Day 9
Percentage of Participants Who Developed a Lower Respiratory Tract Complication	A Lower Respiratory Tract Complication (LRTC) was defined as one of the below as determined by the adjudication committee: Primary RSV lower respiratory tract infection (LRTI); Secondary bacterial LRTI; LRTI due to unusual pathogens; Lower respiratory tract complication of unknown etiology	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality	Participants were considered to have an event if either condition is met: Participant develops a respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) or;; Participant dies prior to or on Day 28	Up to Day 28

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Chemaly RF, Dadwal SS, Bergeron A, Ljungman P, Kim YJ, Cheng GS, Pipavath SN, Limaye AP, Blanchard E, Winston DJ, Stiff PJ, Zuckerman T, Lachance S, Rahav G, Small CB, Mullane KM, Patron RL, Lee DG, Hirsch HH, Waghmare A, McKevitt M, Jordan R, Guo Y, German P, Porter DP, Gossage DL, Watkins TR, Marty FM, Chien JW, Boeckh M. 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. Clin Infect Dis. 2020 Dec 31;71(11):2777-2786. doi: 10.1093/cid/ciz1166.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2015
• Primary Completion (Actual): July 14, 2017
• Study Completion (Actual): July 14, 2017

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Actual): August 6, 2018
• Last Update Submitted That Met QC Criteria: July 10, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Respiratory Syncytial Virus (RSV); Antiviral; Hematopoietic Cell Transplant (HCT); Upper respiratory tract infection
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: GS-US-218-0108; 2014-002474-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No