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

Phase 2
Completed
Conditions
Respiratory Syncytial Virus Infection
Interventions
Drug: Placebo
Registration Number
NCT02254421
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 lower respiratory tract infection (LRTI).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive placebo to match 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.
PresatovirPresatovirParticipants 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.
Primary Outcome Measures
NameTimeMethod
Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9Baseline 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.

Secondary Outcome Measures
NameTimeMethod
Number of Supplemental O2-Free Days Through Day 28Up to Day 28
Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28Up to Day 28
Percentage of All-Cause Mortality Among Participants Through Day 28Up to Day 28

Trial Locations

Locations (17)

University Clinical Basel

🇨🇭

Basel, Switzerland

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

City of Hope

🇺🇸

Duarte, California, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Duke University

🇺🇸

Durham, North Carolina, United States

Seoul Saint Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

Hopital Saint-Louis, APHP

🇫🇷

Paris, France

John Hopkins

🇺🇸

Baltimore, Maryland, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

New York Weill Cornell Medical Center

🇺🇸

New York, New York, United States

Karolinska Institutet

🇸🇪

Stockholm, Sweden

Hopital Foch

🇫🇷

Suresnes, France

Fred Hutchison Cancer Research Center

🇺🇸

Seattle, Washington, United States

CHU de Bordeaux

🇫🇷

Talence, France

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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