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

Phase 3
Completed
Conditions
Influenza
Interventions
Registration Number
NCT06774859
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Baloxavir MarboxilBaloxavir MarboxilParticipants will receive a single oral dose of baloxavir marboxil on Day 1 based on body weight.
OseltamivirOseltamivirParticipants will receive oseltamivir twice a day for 5 days based on body weight.
Primary Outcome Measures
NameTimeMethod
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)Up to Day 29
Secondary Outcome Measures
NameTimeMethod
Change From Baseline in the Amount of Virus RNA (Based on RT-PCR)Baseline (Day 1), Day 2, 4, 6, 10, 15 and 29
Percentage of Participants With Positive Influenza Virus TiterDay 2, 4, 6, 10, 15 and 29
Percentage of Participants With Positive for Influenza Virus as Assessed by RT-PCRDay 2, 4, 6, 10, 15 and 29
Area Under the Curve in Amount of Virus RNA (Based on RT-PCR)Day 1 to Day 29
Area Under the Curve (AUC) in Virus TiterDay 1 to Day 29
Plasma Concentrations of S-033447Up to 72 hours post dose

S-033447 is an active metabolite of baloxavir marboxil.

Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) of S-033447Up to Day 10

S-033447 is an active metabolite of baloxavir marboxil.

Maximum Observed Concentration (Cmax) of S-033447Up to Day 10

S-033447 is an active metabolite of baloxavir marboxil.

Elimination Half-life (t1/2) of S-033447Up to Day 10

S-033447 is an active metabolite of baloxavir marboxil.

Time of Maximum Observed Concentration (Tmax) of S-033447Up to Day 10

S-033447 is an active metabolite of baloxavir marboxil.

Effective Concentration (EC50) of Baloxavir Marboxil Evaluated by ViroSpot™ AssayUp to Day 29
Percentage of Participants with Responses to Palatability and Acceptability QuestionnaireDay 1

A two-question palatability and acceptability questionnaire will be used. The palatability question ask the participant about taste of the medicine with responses from 'Like very much' to 'Dislike Very Much'. The acceptability question asks participants if they would be happy to take the medicine again, with responses as 'Yes', 'No' and 'Not Sure'.

Time to Alleviation of Influenza Signs and SymptomsUp to Day 15

Time to Alleviation of Influenza Signs \& Symptoms is defined as length of time taken from the start of treatment to the point at which all of the following criteria are met \& remain so, for at least 21.5 hours: Score of 0 (no problem) or 1 (minor problem) for cough \& nasal symptoms (Items 14 \&15 of the Canadian Acute Respiratory Illness \& Flu Scale \[CARIFS\]); "Yes" response to the following question on CARIFS: "Since the last assessment has the subject been able to return to day care/school (if applicable), or resume his or her normal daily activity in the same way as performed prior to developing the flu?" (if possible) \& return to afebrile state (tympanic temperature ≤ 37.2°C.

Duration of FeverUp to Day 15

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.

Duration of SymptomsUp to Day 15

Duration of symptoms is 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 to Return to Normal Health and Activity Based on the CARIFS QuestionnaireUp to Day 15

CARIFS parental questionnaire is composed of 18 questions, each with a 4-point ordinal scale (no problem=0 to major problem=3) to measure the duration of illness. Total score ranges from 0 (best possible health) to 54 (worst possible health).

Frequency of Influenza-Related ComplicationsUp to Day 29

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

Percentage of Participants Requiring Antibiotics for Influenza Related ComplicationsUp to Day 29
Time to Cessation of Viral Shedding as Assessed by Virus TiterDay 1 to Day 29
Time to Cessation of Viral Shedding as Assessed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)Day 1 to Day 29
Change From Baseline in Influenza Virus TiterBaseline (Day 1), Day 2, 4, 6, 10, 15 and 29
Polymorphic and Treatment-emergent Amino Acid Substitutions in the PA GeneBaseline (Day 1) up to Day 29

Sanger sequencing of the influenza PA gene will be performed to evaluate the incidence of polymorphic (baseline vs. reference) and treatment-emergent (post-baseline vs. baseline) amino acid substitutions.

Trial Locations

Locations (18)

The First People's Hospital of Changde

🇨🇳

Changde, China

Peoples Hospital of Hunan Province

🇨🇳

Changsha, China

Hunan Provincial Maternal and Child Health Care Hospital

🇨🇳

Changsha, China

Chengdu Women's and Children's Central Hospital

🇨🇳

Chengdu, China

Chongqing University Jiangjin Hospital

🇨🇳

Chongqing City, China

Childern's Hospital of Chongqing Medical University

🇨🇳

Chongqing City, China

Cnpc Central Hospital

🇨🇳

Langfang City, China

Liaocheng people's Hospital

🇨🇳

Liaocheng City, China

Linfen Central Hospital

🇨🇳

Linfen City, China

Liuzhou People's Hospital

🇨🇳

Liuzhou City, China

Ningbo Women and Children's Hospital

🇨🇳

Ningbo City, China

Sanmenxia Central Hospital

🇨🇳

Sanmenxia, China

The Third People's Hospital of Hainan Province

🇨🇳

Sanya, China

The Second Affiliated Hospital of Shantou University Medical College

🇨🇳

Shantou City, China

The First Affiliated Hospital, Shaoyang University

🇨🇳

Shaoyang, China

University of Chinese Academy of Sciences Shenzhen Hospital

🇨🇳

Shenzhen City, China

Xiamen Maternal and Child Health Hospital

🇨🇳

Xiamen City, China

Yuncheng Central Hospital

🇨🇳

Yuncheng, China

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