Presatovir in Lung Transplant (LT) Recipients With Respiratory Syncytial Virus (RSV) Infection

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effect of presatovir on nasal respiratory syncytial virus (RSV) viral load in RSV-positive lung transplant (LT) recipients with acute respiratory symptoms.

Official Title
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A Phase 2b, Randomized, Controlled Trial Evaluating GS-5806 in Lung Transplant (LT) Recipients With Respiratory Syncytial Virus (RSV) Infection

Conditions
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Respiratory Syncytial Virus (RSV)

Intervention / Treatment
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* Drug: Presatovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males and females ≥18 years of age who have received a LT (single or double) or heart/lung transplant > 90 days prior to Screening Confirmed to be RSV-positive by local polymerase chain reaction (PCR) testing (starting from when the upper or lower respiratory tract sample is obtained) ≤ 7 days prior to investigational medicinal product (IMP) administration on Day 1/Baseline New onset or acute worsening, if the symptom is chronic, of at least 1 of the following respiratory symptoms ≤ 7 days prior to IMP administration on Day 1/Baseline: nasal congestion, earache, runny nose, cough, sore throat, shortness of breath, or wheezing A negative local urine or serum pregnancy test for female subjects of childbearing potential at Screening, within 1 day prior to IMP administration. When available, existing local pregnancy test results obtained prior to Screening may be used, provided the testing was completed within 1 day prior to IMP administration Agreement from male and female subjects of childbearing potential who engage in heterosexual intercourse to use protocol specified method(s) of contraception Key Exclusion Criteria: Related to concomitant or previous medication use: Use of any non-marketed (according to region) investigational agents within 30 days, OR use of any investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of Screening, whichever is longer, OR use of any prior investigational RSV vaccines Use of a strong or moderate cytochrome P450 enzyme (CYP) 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 IMP Related to transplant history: • Recipient of any other organ transplant prior to Screening, with the exception of a LT (single or double) or heart/lung transplant Related to medical condition at Screening: Known viral coinfection (including but not limited to influenza, metapneumovirus, human rhinovirus, parainfluenza, cytomegalovirus, or coronavirus) in the upper or lower respiratory tract ≤ 14 days prior to Screening unless discussed with the medical monitor and deemed acceptable Active systemic infection or infectious pneumonia of any etiology (ie, bacterial, viral [other than RSV] or fungal), including aspiration pneumonia, that is considered clinically significant by the investigator unless discussed with the medical monitor and deemed acceptable Related to laboratory values: Clinically significant kidney dysfunction as defined by: An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) study 4 parameter equation obtained from screening laboratory measurements or via local laboratory measurements obtained ≤ 7 days prior to Screening. The eGFR may be manually calculated or the reported eGFR value may be used, but any automatically calculated eGFR must be calculated using the MDRD equation. Clinically significant liver function test abnormalities as defined by an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN) obtained in screening laboratory measurements or via local laboratory measurements obtained ≤ 7 days prior to Screening Clinically significant elevations in total bilirubin (TB), as determined by the investigator Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Presatovir<br>Presatovir 200 mg (4 x 50 mg) on Day 1, followed by 100 mg (2 x 50 mg) from Day 2 to Day 14 | Drug: Presatovir<br>* Tablets administered orally or via nasogastric (NG) tube once daily<br>* Other names: GS-5806;|
| Placebo Comparator: Placebo<br>Placebo tablets for a total of 14 days | Drug: Placebo<br>* Tablets administered orally or via NG tube once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in Participants in the Full Analysis Set |  | Up to 7 days | 
| Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in a Subset of Participants in the Full Analysis Set Whose Duration of RSV Symptoms Prior to the First Dose of Study Drug is ≤ Median |  | Up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-Weighted Average Change in FLU-PRO Score From Day 1/Baseline Through Day 7 | The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms) for the 5-point severity scale and 0 (never) to 4 or more times (always) for the 5-point frequency scale. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor. | Up to 7 days | 
| Percent Change From Study Baseline in FEV1% Predicted Value | FEV1 is defined as forced expiratory volume in the first second. | Baseline; Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus (RSV), Antiviral, Lung Transplant