Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

Respiratory Syncytial Virus Infection 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 Lower Respiratory Tract

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02254421
• Other study ID #: GS-US-218-1502
• Secondary ID: 2014-002475-29
• Status: Completed
• Phase: Phase 2
• Start date: January 31, 2015
• Est. completion date: April 17, 2017

Study information

• Verified date: May 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 lower respiratory tract infection (LRTI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 17, 2017
• Est. primary completion date: April 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Respiratory Syncytial Virus Infection
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Supplemental O2-Free Days Through Day 28		Up to Day 28
Secondary	Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28		Up to Day 28
Secondary	Percentage of All-Cause Mortality Among Participants Through Day 28		Up to Day 28