Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

Phase 2

Recruiting

• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Influenza
• Interventions: Drug: Baloxavir Marboxil; Drug: Oseltamivir

• Registration Number: NCT04712539
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the efficacy of baloxavir marboxil (baloxavir) in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 1 from baseline for treatment of severe influenza infections in immunocompromised hosts (such as hematopoietic cell transplant \[HCT\] recipients and hematological malignancy \[HM\] patients) and compare the main clinical outcome, complicated hospital stay between the intervention arm and control arm.

SECONDARY OBJECTIVES:

I. To compare the efficacy of baloxavir in combination with oseltamivir to oseltamivir monotherapy as measured by changes in influenza viral loads at day 3, 7, 14 and 30 from baseline.

II. To measure the incidence of baloxavir and oseltamivir resistance, development of lower respiratory tract infections (LRTI), oxygen requirement, respiratory failure, changes in microbiome of the upper airway, length of hospital stay and all-cause mortality at day 30 while on baloxavir and/or oseltamivir in these immunocompromised hosts.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive oseltamivir orally (PO) twice daily (BID) for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.

After completion of study, patients are followed up at 30 days.

Study Timeline

• Study First Submitted: 2021-01-13
• Study First Submitted QC: 2021-01-13
• Study First Posted: 2021-01-15
• Study Start: 2021-10-11
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-24
• Primary Completion: 2028-02-28
• Study Completion: 2028-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (oseltamivir, baloxavir marboxil)	Oseltamivir	Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
Arm I (oseltamivir, baloxavir marboxil)	Baloxavir Marboxil	Patients receive oseltamivir PO BID for up to 10 days and baloxavir marboxil PO every 72 hours for a total of 3 doses in the absence of disease progression or unacceptable toxicity.
Arm II (oseltamivir)	Oseltamivir	Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Changes in viral loads	On day 0, 1, 3, 7, 14, and 30	Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.
Incidence of complicated hospital stay	Up to 30 days	Defined as a hospital admission that was either prolonged (greater than 7 days), requiring intensive care unit level of care or death at day 30 as a result of influenza infection.

Secondary Outcome Measures

Name	Time	Method
Progression to lower respiratory tract infections	Up to 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.
Rate of resistance to antiviral agents	Up to 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.
Length of hospital stay	Up to 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.
Rate of respiratory failure	Up to 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.
30-day mortality	At 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.
Changes in microbiome diversity	On day 0, 1, 3, 7, 14, and 30	Analysis of alpha and beta diversity of microbiome will be assessed using Agile Toolkit for Incisive Microbial Analyses. Using Shannon index, we will quantify the alpha diversity of the microbiome. Changes in microbiome diversity will be made by comparing alpha diversity at each time point of sample collection (days 0, 1, 3, 7, 14 and 30).
Oxygen requirement	Up to 30 days	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States