Clinical trial NCT02254421: Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower 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 Lower Respiratory Tract
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infection
Keywords: Respiratory Syncytial Virus (RSV)
Antiviral
Hematopoietic Cell Transplant (HCT)
Lower respiratory tract infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-10-01
Enrollment: 60
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 lower respiratory tract infection (LRTI).


Eligibility criteria: 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.

Primary outcomes:
measure: Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9
timeFrame: Baseline to Day 9
Secondary outcomes:
measure: Number of Supplemental O2-Free Days Through Day 28
timeFrame: Up to Day 28
measure: Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28
timeFrame: Up to Day 28
measure: Percentage of All-Cause Mortality Among Participants Through Day 28
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Chicago
country: United States
facility: University of Chicago
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: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: New York Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
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: Paris
country: France
facility: Hopital Saint-Louis, APHP
city: Suresnes
country: France
facility: Hopital Foch
city: Talence
country: France
facility: CHU de Bordeaux
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Basel
country: Switzerland
facility: University Clinical Basel
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.