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

Respiratory Syncytial Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02254408
• Other study ID #: GS-US-218-0108
• Secondary ID: 2014-002474-36
• Status: Completed
• Phase: Phase 2
• Start date: January 23, 2015
• Est. completion date: July 14, 2017

Study information

• Verified date: July 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: July 14, 2017
• Est. primary completion date: July 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Infection
• Respiratory Syncytial Virus
• Respiratory Syncytial Virus Infections

Intervention

Drug:
• Presatovir
Presatovir 200 mg (4 × 50 mg tablets) administered orally or via nasogastric (NG) tube
• Placebo
Tablets administered orally or via nasogastric tube

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Israel,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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