This is a randomized, double-blind, placebo-controlled pilot study of the efficacy and safety of baloxavir in combination with oseltamivir (standard of care) for the treatment of influenza in allogeneic stem cell transplant patients. Although there are no data about this treatment option currently available, the investigator hypothesizes that combination therapy may be more effective in clearing influenza virus infection and decreasing the rate of emergence of resistant influenza in immunocompromised human hosts.
This is a randomized double-blind placebo-controlled pilot study of the efficacy and safety of baloxavir in combination with oseltamivir (standard of care) for the treatment of influenza in allogeneic stem cell transplant patients. 30 SCT recipients will take part in the study. Participants with be randomly assigned (1:1) to either baloxavir + oseltamivir or baloxavir-matched placebo +oseltamivir. Before randomization, patients will be stratified by hospitalization status and influenza type A (yes/no). Patients in the baloxavir combination arm will receive weight-adjusted baloxavir (40 mg for patients weighing \<80 kg and 80 mg for those weighing ≥80 kg) at baseline and at day 4 and day 7. They will also receive oseltamivir 75 mg twice daily for 10 days. Patients in the baloxavir-matched placebo + oseltamivir arm will receive baloxavir-matched placebo at baseline and at day 3 and day 7and oseltamivir 75 mg twice daily for 10 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2
Weight-adjusted Baloxavir Marboxil (40 mg for patients weighing \<80 kg and 80 mg for those weighing ≥80 kg) at baseline, day 4, and day 7.
Placebo at baseline, day 4, and day 7.
Oseltamivir 75 mg twice daily for 10 days.
Weill Cornell Medicine
New York, New York, United States
Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Quantitative Real Time Polymerase Chain Reaction.
Influenza viral RNA loads will be measured by quantitative real time polymerase chain reaction.
Time frame: Baseline; Day 10
Between-treatment-arm Difference in the Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Quantitative Real Time Polymerase Chain Reaction.
Influenza viral load will be measured by the quantitative real time polymerase chain reaction.
Time frame: Baseline; Day 10
Between-treatment-arm Difference in the Change of Influenza Viral RNA Loads From Baseline at the End of Treatment as Measured by Influenza Plaque Assay (Replicating Virus).
Influenza viral load will be measured by the influenza plaque assay.
Time frame: Baseline; Day 10
Change of Influenza Viral RNA Load From Baseline at Day 4 and Day 7 and 10 in Each Treatment Arm
Influenza viral RNA load will be measured by quantitative real time polymerase chain reaction.
Time frame: Baseline; Day 4; Day 7; Day 10
Difference in Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 Between the Two Treatment Arms as Measured by Quantitative Real Time Polymerase Chain Reaction
Influenza viral RNA load will be measured by quantitative real time polymerase chain reaction.
Time frame: Baseline; Day 4; Day 7; Day 10
Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 as Measured by Influenza Plaque Assay (Replicating Virus) in Each Treatment Arm
Influenza viral load will be measured by the influenza plaque assay (replicating virus).
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Time frame: Baseline; Day 4; Day 7; Day 10
Difference in Change of Influenza Viral Loads From Baseline at Day 4, 7 and 10 Between the Two Treatment Arms as Measured by Influenza Plaque Assay (Replicating Virus)
Influenza viral load will be measured by the influenza plaque assay (replicating virus).
Time frame: Baseline; Day 4; Day 7; Day 10
Time to Improvement of Individual Influenza Symptoms as Assessed by Patient-reported Outcome Measures on a Single Scale
Patients will self-assess the severity of 7 influenza-associated symptoms on a 4-point single scale with 0 indicating no symptoms and higher scores indicating mild, moderate, and severe symptoms. Time to improvement of individual influenza symptoms are defined as the time from the start of treatment to the time when each of the influenza symptoms are alleviated, maintained, or improved for a duration of at least 21.5 hours. These are defined as: pre-existing symptoms (cough, fatigue, or muscle/join pain that existed prior to influenza) that were worse at baseline and had improved at least 1 point from baseline; pre-existing symptoms not worse at baseline that maintained baseline severity; and new symptoms that were alleviated, defined as a symptom score of non (0) or mild (1).
Time frame: Baseline to Day 30
Percentage of Patients Who Experience Each Influenza-related Complications: Hospitalization, Death, Sinusitis, Otitis Media, Bronchitis, and Radiologically-confirmed Pneumonia as an Adverse Event After the Initiation of Study Treatment
A composite score of multiple measures will be used and calculated by count of patients who experience each influenza-related complications. Adverse events will only include those that are determined to be related to the study drug.
Time frame: Day 1 to Day 30
Time to Return to Preinfluenza Health Status
Preinfluenza health status will be measured on a score from 0 (worst possible health) to 10 (normal health \[for someone your age and condition\]).
Time frame: Day 1 to Day 30
Time to Viral Clearance, as Assessed by Difference in Percentage of Participants Positive by Influenza Plaque Assay at Each Time-point (in Each Treatment Group)
Time to viral clearance will be assessed by percentage of participants positive by influenza plaque assay at each time-point.
Time frame: Baseline to Day 30
Time to Viral Clearance, as Assessed by Difference in Percentage of Participants Positive by Quantitative Real Time Polymerase Chain Reaction
Time to viral clearance will be assessed by percentage of participants positive by qPCR at each time-point.
Time frame: Baseline to Day 30
Change of Treatment-emergent Variants of Neuraminidase and Polymerase Known to Confer Antiviral Resistance to Oseltamivir in Each Arm by Direct Next-generation Sequencing Symptoms
Treatment-emergent variants will be identified using direct next-generation sequencing of a comprehensive panel of genes.
Time frame: Baseline to Day 30
Percentage of Participants With Adverse Events (AEs)
Adverse events will only include those that are determined to be related to the study drug and will assess the safety and tolerability of Baloxavir in Combination with SOC treatment.
Time frame: Day 1 to Day 15