Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants With Influenza-Like Symptoms

Hoffmann-La Roche173 enrolled

Overview

This study will evaluate the safety, pharmacokinetics, and efficacy of baloxavir marboxil compared with oseltamivir in a single influenza episode in otherwise healthy pediatric participants (i.e., 1 to \<12 years of age) with influenza-like symptoms.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

173

Conditions

Influenza

Interventions

Baloxavir MarboxilDRUG

Baloxavir marboxil will be administered as oral suspension in a single dose on Day 1. Oseltamivir matching placebo will also be administered as oral suspension twice daily (BID) for 5 days.

OseltamivirDRUG

Oseltamivir will be administered as oral suspension BID for 5 days. Participants receiving oseltamivir will also receive baloxavir marboxil matching placebo as oral suspension, single dose on Day 1.

Eligibility

Sex: ALLMin age: 1 YearMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Aged 1 to \< 12 years at randomization (Day 1). * Written informed consent/assent for study participation obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the patient's level of understanding * Participant able to comply with study requirements, depending on the patient's level of understanding * Participant with a diagnosis of influenza virus infection confirmed by the presence of all of the following: * Fever ≥ 38 degree celsius (tympanic temperature) at screening * At least one respiratory symptom (either cough or nasal congestion) * The time interval between the onset of symptoms and screening is ≤ 48 hours Exclusion Criteria: * Severe symptoms of influenza virus infection requiring inpatient treatment * Concurrent infections requiring systemic antiviral therapy at screening * Require, in the opinion of the investigator, any of the prohibited medication during the study * Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening * Immunization with a live/attenuated influenza vaccine in the 2 weeks prior to randomization * Concomitant treatment with steroids or other immuno-suppressant therapy * Known HIV infection or other immunosuppressive disorder * Uncontrolled renal, vascular, neurologic, or metabolic disease (e.g., diabetes, thyroid disorders, adrenal disease), hepatitis, cirrhosis, or pulmonary disease or participants with known chronic renal failure. * Active cancer at any site * History of organ transplantation * Known allergy to either study drug (i.e., baloxavir marboxil and oseltamivir) or to acetaminophen * Females with child-bearing potential * Participation in a clinical trial within 4 weeks or five half-lives of exposure to an investigational drug prior to screening, whichever is longer

Locations (37)

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Time frame: Up to Day 29

Secondary Outcomes

Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population

Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

Plasma Concentrations of S-033447 - Sparse PK Population

Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.

Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population

Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

Plasma Concentrations of S-033447 - Extensive PK Population

Data from ClinicalTrials.gov

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Central Alabama Research; Pediatrics

Birmingham, Alabama, United States

Harrisburg Family Medical Center

Harrisburg, Arkansas, United States

The Children's Clinic of Jonesboro, P.A.

Jonesboro, Arkansas, United States

The Probe Medical Research

Los Angeles, California, United States

Orange County Research Institute

Ontario, California, United States

Khruz Biotechnology Research Institute

San Diego, California, United States

Avanza Medical Research Center

Pensacola, Florida, United States

Clinical Research Prime

Idaho Falls, Idaho, United States

Cotton O'Neil Clinic; Stormont-Vail Hlth Care

Topeka, Kansas, United States

Kentucky Pediatric Research Center

Bardstown, Kentucky, United States

...and 27 more locations

Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

Time to Alleviation of Influenza Signs and Symptoms

Time to alleviation of influenza signs and symptoms is defined as the length of time taken from the start of treatment to the point at which all of the following criteria are met and remain so for at least 21.5 hours: * A score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms (items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale \[CARIFS\]) * A "yes" response to the following question on the CARIFS: "Since the last assessment has the subject been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu?" * First return to afebrile state (tympanic temperature ≤37.2 degree Celsius \[°C\])

Time frame: Up to Day 15

Duration of Fever

Length of time taken by participants to return to afebrile state \[tympanic temperature ≤ 37.2°C\] and remaining so for at least 21.5 hours.

Time frame: Up to Day 15

Duration of Symptoms

The clinical efficacy of baloxavir marboxil is evaluated by duration of symptoms i.e., alleviation of all symptoms as defined by a score of 0 \[no problem\] or 1 \[minor problem\] and remaining so for at least 21.5 hours, for all 18 symptoms specified in the CARIFS questionnaire.

Time frame: Up to Day 15

Time to Return to Normal Health and Activity

Time to Return to Normal health and activity' is identified by a 'Yes' response to the following question on the CARIFS: "Since the last assessment has the patient been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu?"

Time frame: Up to Day 15

Frequency of Influenza-Related Complications

Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.

Time frame: Up to Day 29

Percentage of Participants With Influenza-Related Complications

Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.

Time frame: Up to Day 29

Percentage of Participants Requiring Antibiotics

Time frame: Up to Day 29

Time to Cessation of Viral Shedding by Virus Titer

Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of any study treatment and first time when the influenza virus titer is below the limit of detection.

Time frame: Day 1 - Day 29

Time to Cessation of Viral Shedding by RT-PCR

Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection.

Time frame: Day 1 - Day 29

Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29

Influenza virus titer (log10TCID50/ML) is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.

Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29

If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)

Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10

Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10

Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29

Time frame: Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

Area Under the Curve in Virus Titer

Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.

Time frame: Day 1 - Day 29

Area Under the Curve in the Amount of Virus RNA (RT-PCR)

AUC in virus RNA (RT-PCR) is defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 10. AUC is calculated using the trapezoidal method similar to AUC in virus titer.

Time frame: Day 1 - Day 10

Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil