Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Chinese Pediatric Participants 1 to <12 Years of Age With Influenza Symptoms

Hoffmann-La Roche100 enrolled

Overview

The purpose of this study is to evaluate the safety of a single dose baloxavir marboxil compared with 5 days of oseltamivir administered twice a day (BID) in Chinese pediatric participants aged 1 to \< 12 years with influenza symptoms.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

100

Conditions

Influenza

Interventions

Baloxavir MarboxilDRUG

Baloxavir marboxil will be administered as oral suspension: 2 milligrams per kilograms (mg/kg) (if weight \< 20 kg), 40 mg (if weight ≥ 20 kg to \< 80 kg), or 80 mg (if weight ≥ 80 kg).

OseltamivirDRUG

Oseltamivir will be administered as oral capsule: 30 mg (if weight ≤15 kg), 45 mg (if weight \> 15 kg to ≥ 23 kg), 60 mg (if weight \> 23 kg to ≤ 40 kg) or 75 mg (if weight \> 40 kg), twice daily (BID) for 5 days.

Eligibility

Sex: ALLMin age: 1 YearMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: * A participant who has a diagnosis of influenza virus infection and meets all the following conditions: * Fever ≥ 38°C (tympanic temperature) at screening * At least one of the respiratory symptoms of influenza virus infection * A rapid influenza diagnostic test (RIDT) or polymerase chain reaction (PCR) shows positive for influenza A/B, e.g., point-of-care/local laboratory results with use of nasal aspirate, throat swab, or nasal drip/droplet (or other appropriate sample) * The time interval between the onset of symptoms and screening is ≤ 48 hours * PCR (-) or antigen test (-) for severe acute respiratory virus-coronavirus 2 (SARS-CoV-2) using point-of-care/local laboratory test with nasal aspirate, throat swab, or nasal drip/droplet (or other appropriate sample) Exclusion Criteria: * A participant having severe influenza virus infection symptoms requiring inpatient treatment * Received systemic corticosteroid or immunosuppressive therapy * Primary immunodeficiency syndrome * History of organ transplantation * Human immunodeficiency virus (HIV) infection * Immunization with a live/attenuated influenza vaccine in 2 weeks prior to randomization * Previous malignancy within the last 5 years or has an active cancer at any site * A participant who received any medications with anti-flu effect such as baloxavir, peramivir, oseltamivir, zanamivir, favipiravir, arbidol, amantadine or traditional Chinese anti-influenza medicines within 30 days before screening * Diagnosed with or suspected SARS-CoV-2 infection, or close contacts of diagnosed or suspected SARS-CoV-2 infected patients * Severe underlying disease or condition potentially affecting study evaluation in the opinion of the investigator/sub-investigator * A participant who received an investigational or unapproved drug product within 30 days or 5 x the half-life before screening, whichever is longer

Locations (16)

The First People's Hospital of Changde

Changde, China

Peoples Hospital of Hunan Province

Changsha, China

Outcomes

Primary Outcomes

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

An AE was defined as any untoward medical occurrence in a participant or clinical study participant temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability or incapacity, was a congenital anomaly or birth defect.

Time frame: Up to Day 29

Secondary Outcomes

Time to Alleviation of Influenza Signs and Symptoms (TTAS)

TTAS was defined as the length of time taken from start of treatment to point at which all of following criteria were met \& remained so for at least 21.5 hours: * Score of 0 (no problem) or 1 (minor problem) for cough \& nasal symptoms (Items 14 \& 15 of Canadian Acute Respiratory Illness and Flu Scale \[CARIFS\]); * A "yes" response to following question- "Since last assessment has participant been able to return to day care/school, or resume his/her normal daily activity in same way as performed prior to developing flu?"; * Return to afebrile state (tympanic temperature ≤ 37.2 degree Celsius \[°C\]). Median time was estimated using Kaplan-Meier (K-M) method.

Time frame: Up to Day 15

Duration of Fever

Duration of fever was defined as the length of time from start of treatment to return to afebrile state (tympanic temperature ≤ 37.2°C) and remaining so for at least 21.5 hours. Participants who were afebrile at baseline (tympanic temperature ≤ 37.2 °C) or whose body temperature was not collected were excluded from the analysis. Median time was estimated using K-M method.

Time frame: Up to Day 15

Duration of Symptoms

Data from ClinicalTrials.gov

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Chengdu Women's and Children's Central Hospital

Chongqing University Jiangjin Hospital

Chongqing, China

Childern's Hospital of Chongqing Medical University

Chongqing, China

Hebei Petro China Central Hospital

Langfang, China

Liaocheng people's Hospital

Liaocheng, China

Linfen Central Hospital

Linfen, China

Liuzhou People's Hospital

Liuzhou, China

Ningbo Women and Children's Hospital

Ningbo, China

...and 6 more locations

Duration of symptoms was defined as the length of time from start of treatment to 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. Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point. Median time was estimated using K-M method.

Time frame: Up to Day 15

Time to Return to Normal Health and Activity Based on the CARIFS Questionnaire

Time to return to normal health and activity was defined as time from start of treatment to normal health and activity. Normal health \& activity was identified by a 'yes' response to the following question on the CARIFS: "Since the last assessment has the participant been able to return to day care/school, or resume his/her normal daily activity in the same way as performed prior to developing the flu?". Median time was estimated using K-M method.

Time frame: Up to Day 15

Number of Participants With Influenza-related Complications

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

Time frame: Up to Day 29

Percentage of Participants Requiring Antibiotics for Influenza-related Complications

Influenza-related complications included death, hospitalization, radiologically-confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, and myositis. Percentages have been rounded off.

Time frame: Up to Day 29

Time to Cessation of Viral Shedding by Virus Titer

Time to cessation of viral shedding by virus titer was defined as the time, in hours, between the initiation of study treatment and the first time when the influenza virus titer was below the lower limit of detection (LLoD) (0.75 log10 tissue culture infectious dose \[TCID\] 50/milliliters \[mL\]). Participants whose virus ribonucleic acid (RNA) did not reach the limit by the last observation timepoint were treated as censored at that timepoint. Median time was estimated using K-M method.

Time frame: Up to Day 29

Time to Cessation of Viral Shedding by Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) Using Samples From Respiratory Swabs

Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of study treatment and the first time when the virus RNA by RT-PCR qualitative result is below the LLoD (qualitative assessment). For the participants with multiple virus types, time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA by RT-PCR qualitative result is negative for all virus types. Participants whose virus RNA did not reach the limit by the last observation timepoint were censored at that timepoint. Median time was estimated using K-M method.

Time frame: Up to Day 29

Change From Baseline in Influenza Virus Titer Over Time Using Samples From Respiratory Swabs

Change from baseline in influenza virus titer (log10 TCID50/mL) on Days 2, 4, 6, 10, and 15 are presented. Influenza virus titer on specified time points was analysed with use of samples from respiratory swabs. If influenza virus titer was less than the lower limit of quantification (LLoQ), the virus titer was imputed as LLoQ - 0.001 (0.749 log10 TCID50/mL). Only participants with a positive virus titer on Day 1 were included in this analysis.

Time frame: Baseline, Days 2, 4, 6, 10, and 15

Change From Baseline in Amount of Virus RNA (RT-PCR) at Each Timepoint Using Samples From Respiratory Swabs

If the amount of virus RNA was less than the LLoQ, the amount of virus RNA was imputed as LLoQ - 0.001 (2.79 log10 vp/mL for influenza A and 2.63 log10 vp/mL for influenza B). If a participant was infected with multiple virus types, the sum of those amounts of virus RNA was used for analysis. Participants positive for virus RNA by RT-PCR on Day 1 were included in this analysis. log10 vp/mL=log 10 virus particles per milliliter.

Time frame: Baseline, Days 2, 4, 6, 10, and 15

Percentage of Participants With Positive Influenza Virus Titer Over Time

Percentage of participants with positive influenza virus titer was defined as the percentage of participants whose influenza virus titer was not less than the LLoD (0.75 log10 TCID50/mL) or positive among those assessed for influenza virus titer on specified timepoints. Analyses were done with use of samples from respiratory swabs. Participants with a positive influenza virus titer on Day 1 were be included in this analysis. Percentages have been rounded off.

Time frame: Baseline, Days 2, 4, 6, 10, and 15

Percentage of Participants Positive by RT-PCR at Each Timepoint Using Samples From Respiratory Swabs

Percentage of participants with positive influenza virus titer was defined as the percentage of participants with a positive qualitative result among those assessed by RT-PCR on specified timepoints. Analyses were done with use of samples from respiratory swabs. Participants positive for virus RNA by RT-PCR on Day 1 were be included in this analysis. Percentages have been rounded off.

Time frame: Baseline, Days 2, 4, 6, 10, and 15

Area Under the Curve (AUC) in Virus Titer

AUC was calculated using the trapezoidal method. Participants with a positive virus titer on Day 1 were included in this analysis. The lower limit was defined as 0.75 log10 TCID50/mL for flu A and flu B. If a participant was infected with multiple virus types, the sum of those virus titers was used for analysis. log10 TCID50/mL\*h=log10 TCID50 per milliliter-hours. Analyses were done with use of samples from respiratory swabs.

Time frame: Up to Day 10

AUC in the Amount of Virus RNA (RT-PCR) Using Samples From Respiratory Swabs

AUC in virus RNA (RT-PCR) AUC was calculated using the trapezoidal method. Participants positive for virus RNA by RT-PCR on Day 1 were included in this analysis. If a participant was infected with multiple virus types, the sum of the amount of virus RNA was used for analysis. log10 vp/mL\*h=log 10 virus particles per milliliter-hours.

Time frame: Up to Day 10

Plasma Concentrations of S-033447 (Active Metabolite)