open-label, active-controlled study of baloxavir in pediatric patients with influenza

JRCT ID: jRCTs011200011

Registered date:20/11/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: influenza
• Date of first enrollment: 12/01/2023
• Target sample size: 200
• Study type: Interventional
• Intervention(s): Patients with a positive by a rapid influenza diagnostic test (RIDT) or by an influenza test method covered by insurance, such as telescope for endoscopy and moderate or severe influenza symptoms and a negative SARS-CoV -2 test are randomly assigned to receive a single dose of baloxavir or oseltamivir, and the baloxavir group is to receive a single dose of baloxavir and the oseltamivir group is to receive oseltamivir 2 times daily for 5 days.

Outcome(s)

• Primary Outcome: Time to alleviation of symptom

Secondary Outcome

1) Time to continuous resolution of influenza symptoms (Cough, "Nasal discharge/nasal congestion", "body temperature") (last at least 72 hours)
- It is defined as the time from the start of administration of the test drug until the symptoms of influenza disappear. Resolution of symptoms is defined as the time point of resolution of influenza symptoms when cough and "Nasal discharge/nasal congestion" are assessed as 0 (None) or 1 (mild) and the clinical condition of the more than 37.5 degrees body temperature has been maintained for at least 72 hours.
2) Time to return to normal temperature (last at least 12 hours)
- It is defined as the time from the start of the test drug administration to normal temperature (more than 37.5 degrees). Recovery to normal body temperature is defined as the time to return to normal body temperature if the subject's self-measured body temperature falls below 37.5 degrees and has been present for at least 12 hours.
3) Time to continuous return to normal temperature (last at least 72 hours)
- It is defined as the time from the start of the test drug administration to normal temperature (more than 37.5 degrees). Recovery to normal body temperature is the time to return to normal body temperature if the subject's self-measured body temperature falls below 37.5 degrees and has been present for at least 72 hours.
4) Whether pyrexia was resolved to normal more than 37.5 degrees at each time point
- Percentage of patients with a temperature more than 37.5 degrees at each time point.
5) Body temperature at each time point
- At each time point, the mean and 95 percentage confidence intervals for body temperature in each treatment group and the between-group difference in mean body temperature and its 95 percentage confidence interval should be calculated.
6) Time to resolution of 7 symptoms of influenza (Cough, "sore throat", "headache", "Nasal discharge/nasal congestion", "Fever or chills", "Pain in muscles or joints", "tiredness")
- It is defined as the time from the start of administration of the test drug until the symptoms of influenza 7 symptoms disappear. The elimination of influenza symptoms is defined as the time point when all 7 influenza symptoms are evaluated as 0 (None) or 1 (mild), and if the state has been maintained for at least 21.5 hours, the time point when the 7 influenza symptoms are eliminated is defined as the time point when the 7 influenza symptoms are eliminated.
7) Time to resolution of each influenza symptom
- It is defined as the time from the start of administration of the test drug until each influenza symptom disappears. The elimination of influenza symptoms is defined as the time point at which each influenza symptom (Cough, "sore throat", "headache", "Nasal discharge/nasal congestion", "Fever or chills", "Pain in muscles or joints", "tiredness") is evaluated to be 0 (None) or 1 (mild), and if the state has been maintained for at least 21.5 hours, the time point at which each symptom is eliminated is defined as the time point at which each symptom is eliminated.
8) Presence or absence of flu-related complications (Radiographically confirmed pneumonia, bronchitis, sinusitis, and otitis media)
- It is defined as the percentage of study subjects who developed any flu-related complication (Sinusitis, otitis media, bronchitis, and radiographically confirmed pneumonia) after the start of treatment with the study drug and the percentage of study subjects who developed each flu-related complication.
9) Presence or absence of influenza-related complications unique to pediatric patients (Influenza encephalitis or encephalopathy, febrile convulsion, myositis)
- It is defined as the percentage of study subjects who developed any pediatric patient-specific flu-related complication (Influenza encephalitis or encephalopathy, febrile convulsion, myositis) after the start of study drug administration and the percentage of study subjects who developed each pediatric patient-specific flu-related complication.
10) Death or hospitalization due to influenza-related complications and influenza-related complications unique to pediatric patients
- It is defined as the proportion of research subjects who died or were hospitalized due to influenza-related complications after the start of study drug administration, the proportion of research subjects who died, and the proportion of research subjects who were hospitalized.
11) Use or nonuse of antibiotics
- Defined as the percentage of study subjects who received systemic antibiotics for infections secondary to influenza virus infection after the start of study drug administration.

Key inclusion & exclusion criteria

• Age minimum: >= 6age old
• Age maximum: < 12age old
• Gender: Both

Include criteria

Patients meeting all of the following criteria are selected.
1) A patient who have provided written consent to participate in clinical research from a proxy consenter.
2) Male or female patients aged 6 to 11 years at the time of acquisition of the Ascent according to consent and age.
3) Patients who met all of the following criteria and were diagnosed with influenza virus infection.
- Fever is more than 38 degrees (axillary temperature) at screening
- In patients aged 6 to 11 years; at least one of respiratory symptoms (cough, nasal discharge/nasal congestion) associated with influenza virus infection are present with a severity of moderate or greater.
- Positive rapid influenza diagnostic test (RIDT) with nasal swab, nasal aspirate, throat swab, or nasal drip (Other appropriate samples) or positive by an influenza test method covered by insurance, such as telescope for endoscopy.
4) Patients within 48 hours of onset (At the time of screening). However, onset is defined as the first confirmed fever of 37.5 degree centigrade or higher.
5) Patients judged by the investigator or subinvestigator (Investigators, etc.) to be able to take (swallowing) Baloxavir tablets and Oseltamivir capsules,tablets or dry syrup.
6) A parent/guardian who is willing and able to comply with the research requirements at the discretion of the investigator, etc.
7) Patients who are able to comply with the study requirements, depending on their level of understanding.
8) Patients who weigh 10 kg or more at screening.

Exclude criteria

Patients who meet any of the following criteria are excluded:.
1) Patients with severe symptoms due to influenza virus infection who are considered to require inpatient treatment.
2) Patients with chronic respiratory disease including uncontrolled bronchial asthma.
3) Patients with hepatitis/cirrhosis.
4) Patients with neurological disorders and neurodevelopmental disorders (Including brain, spinal, peripheral, and muscle disorders).
5) Patients with endocrine disorders (Diabetes, thyroid disease, adrenal gland abnormalities, etc.).
6) Patients with heart disease (Congenital heart disease, congestive heart failure, coronary artery disease, etc., excluding patients with hypertension only) during drug therapy.
7) Patients receiving systemic corticosteroids or immunosuppressive therapy.
8) Patients with primary immunodeficiency syndrome.
9) Patients with severe renal impairment (CCr: more than 30 (mL/min) or eGFR more than 30 (mL/min/1.73 m2)).
10) Patients with human immunodeficiency virus (HIV) infection.
11) Patients with malignancy within the past 5 years
12) Patients with consciousness disturbed, abnormal behavior * (Sudden start, jump, or other unexpected behavior that, if not stopped, may affect life) or convulsions at the time of screening, or those complicated by encephalitis or encephalopathy.
*"Nationwide trend research on abnormal behavior during influenza-like illness"
13) Patients with a history of encephalitis/encephalopathy, epilepsy not controlled with antiepileptic drugs, or abnormal behavior associated with influenza virus infection * (Sudden start, jump, or other unexpected behavior that, if not stopped, may affect life) within the past 2 years.
*"Nationwide trend research on abnormal behavior during influenza-like illness"
14) Patients with infections requiring systemic antimicrobial therapy and/or antiviral (Exclude anti-influenza drugs) therapy at screening.
15) Patients judged by the investigator etc. to require the use of prohibited concomitant drugs during the study period.
16)Patients who received valoxavir (Zofruza), peramivir (RAPIACTA), raninamivir (Inaville), oseltamivir (Tamiflu), zanamivir (Relenza), or amantadine (Simmetrel) within 30 days before screening.
17) Patients with allergies to anti-influenza virus drugs and/or acetaminophen and/or a history of clinically relevant intolerance.
18) Patients with SARS-CoV -2 positivity or suspected COVID-19.
(The SARS-CoV -2 rapid diagnostic test should be performed according to the New Coronavirus Infection COVID-19 Clinical Practice Guide (Medical Guide Review Committee) and negative for SARS-CoV -2 at entry.)
19) Patients with a severe underlying disorder that may affect evaluation.
20) Patients who have difficulty drawing blood from veins.
21) Patients person who have received the study drug or unapproved drug for 30 days or has not passed 5 times the half-life at the time of screening.
22) Patients with a disease or condition determined by the investigator, etc. to be difficult to ensure patient safety or the quality of the study data.
23) Patients judged to be inappropriate to participate in the clinical study by the investigator, etc.
24) A post-menarche female patient who wishes to become pregnant during pregnancy or during a clinical study. Or a lactating woman.

Related Information

• Primary Sponsor: Ishiguro Nobuhisa
• Source(s) of Monetary Support: SHIONOGI &amp; CO., LTD.