Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract
- Registration Number
- NCT02254408
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 189
- 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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Presatovir 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. Placebo 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.
- Primary Outcome Measures
Name Time Method Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9 Baseline; 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.
Percentage of Participants Who Developed a Lower Respiratory Tract Complication Up to Day 28 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
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality Up to Day 28 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
Trial Locations
- Locations (68)
City of Hope
🇺🇸Duarte, California, United States
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Universitario USP
🇧🇷Sao Paulo, Brazil
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Karolinska Institutet
🇸🇪Stockholm, Sweden
VUmc cancer center
🇳🇱Amsterdam, Netherlands
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Chang Gung Medical Foundation-LinKou Branch
🇨🇳Taoyuan, Taiwan
Stanford University
🇺🇸Stanford, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
New York Presbyterian Hospital Cornell Medical Center
🇺🇸New York, New York, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Australia
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, Brazil
Fundação Antonio Prudente - Hospital do Câncer AC Camargo
🇧🇷São Paulo, Brazil
Fundacao Faculdade Regional Medicina de Sao Jose do Rio Preto
🇧🇷São Paulo, Brazil
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
Hopital Saint-Louis, APHP
🇫🇷Paris, France
Tom Baker Cancer Centre
🇨🇦Calgary, Canada
CHU de Bordeaux
🇫🇷Bordeaux, France
Institut Universitaire du Cancer Oncopole
🇫🇷Toulouse, France
Hopital Foch
🇫🇷Suresnes, France
Universitatsklinikum Wurzburg
🇩🇪Wurzburg, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Erasmus Medical Center (Rotterdam)
🇳🇱Rotterdam, Netherlands
UMC National University Health System
🇸🇬Singapore, Singapore
Hospital universitario Virgen del Rocio
🇪🇸Seville, Spain
Singapore General Hospital
🇸🇬Singapore, Singapore
University Clinic Basel
🇨🇭Basel, Switzerland
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
King's College Hospital
🇬🇧London, United Kingdom
Loyola University
🇺🇸Maywood, Illinois, United States
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Leeds Teaching Hospitals Trust
🇬🇧Leeds, United Kingdom
Hospital Santa Marcelina
🇧🇷São Paulo, Brazil
Instituto Brasileiro de Controle do Câncer-IBCC
🇧🇷São Paulo, Brazil
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
UCLA David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
NorthSide Medical Center
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
John Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Massachusetts Memorial Cancer Center
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University
🇺🇸Durham, North Carolina, United States
University Hospital Case Medical
🇺🇸Cleveland, Ohio, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Transplant Institute (SCRI)
🇺🇸San Antonio, Texas, United States
Fred Hutchison Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of