Clinical trial NCT02254408: Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus
Keywords: Respiratory Syncytial Virus (RSV)
Antiviral
Hematopoietic Cell Transplant (HCT)
Upper respiratory tract infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-10-01
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9
timeFrame: Baseline; Day 9
measure: Percentage of Participants Who Developed a Lower Respiratory Tract Complication
timeFrame: Up to Day 28
Secondary outcomes:
measure: Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: NorthSide Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: University of Massachusetts Memorial Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital Case Medical
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute (SCRI)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchison Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Sao Paulo
country: Brazil
facility: Hospital Universitario USP
city: São Paulo
country: Brazil
facility: Fundacao Faculdade Regional Medicina de Sao Jose do Rio Preto
city: São Paulo
country: Brazil
facility: Fundação Antonio Prudente - Hospital do Câncer AC Camargo
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Câncer-IBCC
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Paris
country: France
facility: Hopital Saint-Louis, APHP
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Oncopole
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: VUmc cancer center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center (Rotterdam)
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: UMC National University Health System
city: Seville
country: Spain
facility: Hospital universitario Virgen del Rocio
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Basel
country: Switzerland
facility: University Clinic Basel
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-LinKou Branch
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals Trust
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.