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

Efficacy of Combination Baloxovir and Oseltamivir Therapy in Influenza Infected Immunocompromised Hosts

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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Influenza
• Intervention / Treatment: Drug: Baloxavir Marboxil; Drug: Oseltamivir

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roy F. Chemaly, MD,MPH; Phone Number: 713-792-6830; Email: rfchemaly@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Roy F. Chemaly, MD,MPH; Phone Number: 713-792-6830; Email: rfchemaly@mdanderson.org
      • Principal Investigator: Roy F. Chemaly, MD,MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Hematopoeitic cell transplant recipients OR hematological malignancy patients
2. Diagnosed with influenza ⱡ
3. Evidence of LRTI* or high risk upper respiratory tract infection (URTI)**

ⱡ A positive multiplex PCR for influenza is required to confirm a diagnosis of influenza infection.

* LRTI will be defined as influenza cases that have evidence of disease below the level of the trachea on either imaging only (possible LRTI), imaging and microbiological evidence of lower airway disease with a bronchoscopy (probable LRTD) or pathological evidence of disease via biopsy (proven LRTI).

** High risk URI will be defined as those cases of influenza that do not have microbiological nor radiological evidence of LRTI, yet they have an immunodeficiency scoring index (ISI) of 3 or greater as defined by Shah D et al (19) for HCT recipients or severe neutropenia (ANC ≤500 cells/ml) and/or lymphopenia (ALC ≤200 cells/ml) for HM patients.

Exclusion criteria:

1. Patient requires mechanical ventilation at time of enrollment
2. Patient is younger than the age of 12 years old
3. The patient is unable to tolerate oral therapy
4. The patient is pregnant at screening ( Positive serum β-HCG (beta-human chorionic gonadotropin) test for women of child-bearing potential).
5. The patient is on a prohibited medication. These include Influenza antiviral drugs with the exception of oseltamivir and baloxavir (such as peramivir, laninamivir, zanamivir, rimantadine, umifenovir or amantadine) and herbal therapies.
6. The patient is unable to consent will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (oseltamivir, 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.	Drug: Baloxavir Marboxil; Given PO; Other Names: BXM; Xofluza; Drug: Oseltamivir; Given PO
Active Comparator: Arm II (oseltamivir); Patients receive oseltamivir PO BID for up to 10 days in the absence of disease progression or unacceptable toxicity.	Drug: Oseltamivir; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in viral loads	Will be measured via repeat nasopharyngeal swabs at each follow up on day 0, 1, 3, 7, 14 and 30 for influenza quantification.	On day 0, 1, 3, 7, 14, and 30
Incidence of complicated hospital stay	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.	Up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of resistance to antiviral agents	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Progression to lower respiratory tract infections	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Length of hospital stay	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Oxygen requirement	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
Rate of respiratory failure	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	Up to 30 days
30-day mortality	Will compare variables between the interventional and control groups using Fischer's exact test or Wilcoxon rank sum test when appropriate.	At 30 days
Changes in microbiome diversity	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).	On day 0, 1, 3, 7, 14, and 30

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Roy F Chemaly, MD,MPH, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir; Baloxavir
• Other Study ID Numbers: 2020-0919 (Other Identifier: M D Anderson Cancer Center); NCI-2020-13918 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No