Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower 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 Lower 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 lower respiratory tract infection (LRTI).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Hopital Saint-Louis, APHP
  • Suresnes, France
    • Hopital FOCH
  • Talence, France, 33404
    • CHU de Bordeaux
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul Saint Mary's Hospital
• Sweden
  • Stockholm, Sweden
    • Karolinska Institutet
• Switzerland
  • Basel, Switzerland
    • University Clinical Basel
• United States
  • California
    • Duarte, California, United States
      • City of Hope
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States
      • John Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States
      • University of Minnesota
  • New York
    • New York, New York, United States
      • New York Weill Cornell Medical Center
  • North Carolina
    • Durham, North Carolina, United States
      • Duke University
  • Texas
    • Houston, Texas, United States
      • MD Anderson Cancer Center
  • 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

Key Inclusion Criteria:

• Received an autologous or allogeneic HCT using any conditioning regimen
• Evidence of new abnormalities on chest X-ray obtained < 48 hours prior to screening, determined to be consistent with LRTI by the local radiologist, relative to the most recent previous chest X-ray. If chest X-ray is not available, a chest X-ray must be obtained for screening.
• Documented RSV in both the upper (eg, nasal swab, nasopharyngeal swab, nasal wash) and lower (eg, induced sputum, bronchoalveolar lavage, lung biopsy, but not spontaneous sputum) respiratory tract as determined by local testing (eg, polymerase chain reaction, direct fluorescence antibody, respiratory viral panel assay, or culture). All samples must have been collected ≤ 6 days prior to Day 1, or as determined at screening as per protocol.
• An informed consent document signed and dated by the participant or a legal guardian of the participant and 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

Key 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
• Use of a moderate or strong cytochrome P450 enzyme inducer including but not limited to rifampin, St. John's Wort, carbamazepine, phenytoin, efavirenz, bosentan, etravirine, modafinil, and nafcillin, within 2 weeks prior to the first dose of study drug

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 conditions:

• Requiring invasive mechanical ventilation at the time of randomization
• Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus), from the lower respiratory tract sample as determined by local testing
• 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 individuals without an NG 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 to match 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: Placebo; Placebo to match presatovir 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 Viral (RSV) Load From Baseline 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 factors.	Baseline to Day 9

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Supplemental O2-Free Days Through Day 28	Up to Day 28
Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28	Up to Day 28
Percentage of All-Cause Mortality Among Participants Through Day 28	Up to Day 28

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Marty FM, Chemaly RF, Mullane KM, Lee DG, Hirsch HH, Small CB, Bergeron A, Shoham S, Ljungman P, Waghmare A, Blanchard E, Kim YJ, McKevitt M, Porter DP, Jordan R, Guo Y, German P, Boeckh M, Watkins TR, Chien JW, Dadwal SS. 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 Infection of the Lower Respiratory Tract. Clin Infect Dis. 2020 Dec 31;71(11):2787-2795. doi: 10.1093/cid/ciz1167.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2015
• Primary Completion (Actual): April 17, 2017
• Study Completion (Actual): April 17, 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): September 24, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Respiratory Syncytial Virus (RSV); Antiviral; Hematopoietic Cell Transplant (HCT); Lower respiratory tract infection
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Disease Attributes; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: GS-US-218-1502; 2014-002475-29 (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