Back to resultsStudy to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms
Primary Purpose
Influenza
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Baloxavir Marboxil
Sponsored by
About this trial
This is an interventional treatment trial for Influenza
Eligibility Criteria
Inclusion Criteria:
- Age from birth to < 1 year at screening
- Written informed consent for study participation obtained from participant's parents or legal guardian
- Parent/guardian willing and able to comply with study requirements, in the investigator's judgment
Participants with a diagnosis of influenza virus infection confirmed by the presence of all of the following:
- In the investigator's judgement there is a clinical suspicion of influenza
- At least one respiratory symptom (either cough or coryza)
(b) Positive prescreening influenza test (RIDT or PCR) performed within 48 hours of screening
- Participants with a negative prescreening COVID-19 test (RAT or PCR) within 48 hours of screening
- The time interval between the onset of symptoms and screening is ≤ 96 hours (the onset of symptoms is defined as the time when body temperature first exceeded 37.5°C if known, or the time when the first symptom was noticed by the parent or caregiver)
Exclusion Criteria:
- Hospitalized for complications of influenza or significant comorbidities
- Concurrent infections requiring systemic antiviral therapy at screening
- Require, in the opinion of the investigator, any of the prohibited medication during the study
- Preterm neonates (born at < 37 weeks gestation) and/or weighing < 2.5 kg at screening
- Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening
- Immunization with a live/attenuated influenza vaccine during the 2 weeks prior to screening
- 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 transplant
- Known hypersensitivity to study drug (i.e., baloxavir marboxil) or to acetaminophen
- Participation in a clinical trial within 4 weeks or five half-lives of exposure to an investigational drug prior to screening, whichever is longer
Sites / Locations
- The Children's Clinic of Jonesboro, P.A.
- Usf Health
- Clinical Research Prime
- Ann & Robert H. Lurie Children's Hospital of Chicago;Division of Infectious Disease
- Kentucky Pediatric Research Center
- Oak Cliff Research Company, LLC
- Mercury Clinical Research
- Tekton Research
- MHAT Stamen Iliev AD
- SHAT for Pneumo-Phtysiatric Diseases ?Dr. Dimitar Gramatikov?; Dept. of Pulmonology and Phtisiatrics
- ICIMED Instituto de Investigación en Ciencias Médicas
- TAYS Lastenklinikka; Lasten lääketutkimuskeskus Peetu
- Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic
- Hospital Infantil de Mexico; Infectology
- NZOZ Salmed
- Samodzielny Zespol Publicznych Zakladow Opieki Zdrowotnej im. Dzieci Warszawy w Dziekanowie Lesnym
- Wojewodzki Szpital Obserwacyjno-Zakazny; Oddzia? Pediatrii, Chorób Infekcyjnych i Hepatologii
- IN VIVO Sp. z o.o.
- NZOZ Vitamed
- The scientific-research institute of epidemiology; Infectious clinical hospital ?2 of Moscow H.D.
- Global Clinical Trials; Clinical Trials
- GAMA; Clinical Research
- Peermed Clinical Trial Centre
- Metropolitan Clinical Research Institute
- Pholosho Netcare; Netcare Hospital
- Setshaba Research Centre; Clinical Research
- Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
- Hospital Universitario 12 de Octubre; Servicio de Pediatria
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Baloxavir Marboxil
Arm Description
Participants will receive single oral dose of baloxavir marboxil on Day 1 (based on body weight and age).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Plasma Concentrations of Baloxavir Marboxil and S-033447
Area Under the Concentration to Time Curve from Time 0 to Infinity (AUC0-inf) of baloxavir marboxil and S-033447
Maximum Plasma Concentration (Cmax) of baloxavir marboxil and S-033447
Time to Maximum Plasma Concentration (Tmax) of baloxavir marboxil and S-033447
Apparent Half-Life (T1/2) of baloxavir marboxil and S-033447
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])
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.
Duration of Symptoms
The 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 to Return to Normal Health and Activity
Frequency of Influenza-Related Complications
The influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Percentage of Participants Requiring Antibiotics
Time to Cessation of Viral Shedding by Virus Titer and by RT-PCR
Change from Baseline in Influenza Virus Titer and in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29
Percentage of Participants with Positive Influenza Virus Titer and Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29
Area Under the Curve in Virus Titer and in the Amount of Virus RNA (RT-PCR)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03653364
Brief Title
Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms
Official Title
A Multicenter, Single-Arm, Open-Label Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Otherwise Healthy Pediatric Patients From Birth to < 1 Year With Influenza-Like Symptoms
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 23, 2019 (Actual)
Primary Completion Date
April 3, 2023 (Actual)
Study Completion Date
April 3, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety, pharmacokinetics and efficacy of baloxavir marboxil in healthy pediatric participants from birth to <1 year with influenza like symptoms
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Baloxavir Marboxil
Arm Type
Experimental
Arm Description
Participants will receive single oral dose of baloxavir marboxil on Day 1 (based on body weight and age).
Intervention Type
Drug
Intervention Name(s)
Baloxavir Marboxil
Intervention Description
Participants will receive single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Participants will be recruited in parallel to the following three cohorts:
Cohort I: ≥ 3 months to < 12 months old (minimum 8 participants): 2 mg/kg
Cohort II: ≥ 4 weeks to < 3 months old (minimum 4 patients): 1 mg/kg
Cohort III: birth to < 4 weeks old (minimum 4 patients): 1 mg/kg
Primary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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 Outcome Measure Information:
Title
Plasma Concentrations of Baloxavir Marboxil and S-033447
Time Frame
Day 2 and Day 4
Title
Area Under the Concentration to Time Curve from Time 0 to Infinity (AUC0-inf) of baloxavir marboxil and S-033447
Time Frame
Up to Day 10
Title
Maximum Plasma Concentration (Cmax) of baloxavir marboxil and S-033447
Time Frame
Up to Day 10
Title
Time to Maximum Plasma Concentration (Tmax) of baloxavir marboxil and S-033447
Time Frame
Up to Day 10
Title
Apparent Half-Life (T1/2) of baloxavir marboxil and S-033447
Time Frame
Up to Day 10
Title
Time to Alleviation of Influenza Signs and Symptoms
Description
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
Title
Duration of Fever
Description
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
Title
Duration of Symptoms
Description
The 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
Title
Time to Return to Normal Health and Activity
Time Frame
Up to Day 15
Title
Frequency of Influenza-Related Complications
Description
The influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time Frame
Up to Day 29
Title
Percentage of Participants Requiring Antibiotics
Time Frame
Up to Day 29
Title
Time to Cessation of Viral Shedding by Virus Titer and by RT-PCR
Time Frame
Day 1 - Day 29
Title
Change from Baseline in Influenza Virus Titer and in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29
Time Frame
Baseline, Day 2, 4, 6, 10, 15, 29
Title
Percentage of Participants with Positive Influenza Virus Titer and Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29
Time Frame
Day 2, 4, 6, 10, 15, 29
Title
Area Under the Curve in Virus Titer and in the Amount of Virus RNA (RT-PCR)
Time Frame
Day 1 - Day 29
10. Eligibility
Sex
All
Maximum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age from birth to < 1 year at screening
Written informed consent for study participation obtained from participant's parents or legal guardian
Parent/guardian willing and able to comply with study requirements, in the investigator's judgment
Participants with a diagnosis of influenza virus infection confirmed by the presence of all of the following:
In the investigator's judgement there is a clinical suspicion of influenza
At least one respiratory symptom (either cough or coryza)
(b) Positive prescreening influenza test (RIDT or PCR) performed within 48 hours of screening
Participants with a negative prescreening COVID-19 test (RAT or PCR) within 48 hours of screening
The time interval between the onset of symptoms and screening is ≤ 96 hours (the onset of symptoms is defined as the time when body temperature first exceeded 37.5°C if known, or the time when the first symptom was noticed by the parent or caregiver)
Exclusion Criteria:
Hospitalized for complications of influenza or significant comorbidities
Concurrent infections requiring systemic antiviral therapy at screening
Require, in the opinion of the investigator, any of the prohibited medication during the study
Preterm neonates (born at < 37 weeks gestation) and/or weighing < 2.5 kg at screening
Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening
Immunization with a live/attenuated influenza vaccine during the 2 weeks prior to screening
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 transplant
Known hypersensitivity to study drug (i.e., baloxavir marboxil) or to acetaminophen
Participation in a clinical trial within 4 weeks or five half-lives of exposure to an investigational drug prior to screening, whichever is longer
Facility Information:
Facility Name
The Children's Clinic of Jonesboro, P.A.
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
Facility Name
Usf Health
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Clinical Research Prime
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago;Division of Infectious Disease
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Kentucky Pediatric Research Center
City
Bardstown
State/Province
Kentucky
ZIP/Postal Code
40004
Country
United States
Facility Name
Oak Cliff Research Company, LLC
City
Dallas
State/Province
Texas
ZIP/Postal Code
75218
Country
United States
Facility Name
Mercury Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77036-3316
Country
United States
Facility Name
Tekton Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
MHAT Stamen Iliev AD
City
Montana
ZIP/Postal Code
3400
Country
Bulgaria
Facility Name
SHAT for Pneumo-Phtysiatric Diseases ?Dr. Dimitar Gramatikov?; Dept. of Pulmonology and Phtisiatrics
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
ICIMED Instituto de Investigación en Ciencias Médicas
City
San José
ZIP/Postal Code
10108
Country
Costa Rica
Facility Name
TAYS Lastenklinikka; Lasten lääketutkimuskeskus Peetu
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Facility Name
Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic
City
Petach Tikva
ZIP/Postal Code
4931807
Country
Israel
Facility Name
Hospital Infantil de Mexico; Infectology
City
Mexico City
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
06720
Country
Mexico
Facility Name
NZOZ Salmed
City
??czna
ZIP/Postal Code
21-010
Country
Poland
Facility Name
Samodzielny Zespol Publicznych Zakladow Opieki Zdrowotnej im. Dzieci Warszawy w Dziekanowie Lesnym
City
?omianki
ZIP/Postal Code
05-092
Country
Poland
Facility Name
Wojewodzki Szpital Obserwacyjno-Zakazny; Oddzia? Pediatrii, Chorób Infekcyjnych i Hepatologii
City
Bydgoszcz
ZIP/Postal Code
85-030
Country
Poland
Facility Name
IN VIVO Sp. z o.o.
City
Bydgoszcz
ZIP/Postal Code
85-048
Country
Poland
Facility Name
NZOZ Vitamed
City
Bydgoszcz
ZIP/Postal Code
85-079
Country
Poland
Facility Name
The scientific-research institute of epidemiology; Infectious clinical hospital ?2 of Moscow H.D.
City
Moskva
State/Province
Moskovskaja Oblast
ZIP/Postal Code
111123
Country
Russian Federation
Facility Name
Global Clinical Trials; Clinical Trials
City
Gauteng
ZIP/Postal Code
0001
Country
South Africa
Facility Name
GAMA; Clinical Research
City
Germiston
ZIP/Postal Code
1401
Country
South Africa
Facility Name
Peermed Clinical Trial Centre
City
Kempton Park
ZIP/Postal Code
1619
Country
South Africa
Facility Name
Metropolitan Clinical Research Institute
City
Polokwane
ZIP/Postal Code
0699
Country
South Africa
Facility Name
Pholosho Netcare; Netcare Hospital
City
Polokwane
ZIP/Postal Code
0699
Country
South Africa
Facility Name
Setshaba Research Centre; Clinical Research
City
Pretoria
ZIP/Postal Code
0152
Country
South Africa
Facility Name
Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
City
Santiago de Compostela
State/Province
LA Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Pediatria
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms
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