Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms

Hoffmann-La Roche49 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Influenza

Interventions

Baloxavir MarboxilDRUG

Participants will receive single oral dose of baloxavir marboxil on Day 1 based on body weight and age. Participants aged ≥ 3 months to \<12 months old received baloxavir marboxil, 2 milligrams per kilograms (mg/kg). Participants from birth to \< 4 weeks old and ≥ 4 weeks to \< 3 months old received baloxavir marboxil, 1 mg/kg.

Eligibility

Sex: ALLMax age: 1 Year

Medical Language ↔ Plain English

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: 1. In the investigator's judgement there is a clinical suspicion of influenza 2. 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

Locations (27)

Outcomes

Primary Outcomes

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

An 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 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: From Day 1 up to Day 29

Secondary Outcomes

Plasma Concentrations of Baloxavir Marboxil and S-033447

S-033447 is an active metabolite of baloxavir marboxil.

Time frame: 0.5 to 2 hours post dose on Day 1; 24 hours (Day 2) and 72 hours (Day 4) post dose, Day 6 and Day 10

Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil and S-033447

S-033447 is an active metabolite of baloxavir marboxil.

Time frame: Up to Day 10

Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil and S-033447

S-033447 is an active metabolite of baloxavir marboxil.

Time frame: Up to Day 10

Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil and S-033447

S-033447 is an active metabolite of baloxavir marboxil.

Time frame: Up to Day 10

Data from ClinicalTrials.gov

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

Jonesboro, Arkansas, United States

Usf Health

Tampa, Florida, United States

Clinical Research Prime

Idaho Falls, Idaho, United States

Ann & Robert H. Lurie Children's Hospital of Chicago;Division of Infectious Disease

Chicago, Illinois, United States

Kentucky Pediatric Research Center

Bardstown, Kentucky, United States

Oak Cliff Research Company, LLC

Dallas, Texas, United States

Mercury Clinical Research

Houston, Texas, United States

Tekton Research

San Antonio, Texas, United States

MHAT Stamen Iliev AD

Montana, Bulgaria

SHAT for Pneumo-Phtysiatric Diseases ?Dr. Dimitar Gramatikov?; Dept. of Pulmonology and Phtisiatrics

Rousse, Bulgaria

...and 17 more locations

Apparent Half-Life (T1/2) of Baloxavir Marboxil and S-033447

S-033447 is an active metabolite of baloxavir marboxil.

Time frame: Up to Day 10

Time to Alleviation of Influenza Signs and Symptoms

Time to alleviation of influenza signs and symptoms was defined as the length of time taken from the start of treatment to the point at which all of the following criteria were met and remained for at least 21.5 hours: * A score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms for 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 participant 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 \[°C\]). Median time was estimated from the Kaplan-Meier curve. Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Time frame: Day 1 up to Day 15

Duration of Fever

Duration of fever was defined as the 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 after onset. Participants who did not have fever at baseline or whose body temperature was not collected were excluded from the analysis. Median time was estimated from the Kaplan-Meier curve.

Time frame: Day 1 up to Day 15

Duration of Symptoms

The efficacy of baloxavir marboxil was 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 (Poor appetite; Not sleeping well; Irritable, cranky, fussy; Feels unwell; Low energy, tired; Not playing well; Crying more than usual; Needing extra care; Clinginess; Headache; Sore throat; Muscle aches or pains; Fever; Cough; Nasal congestion, runny nose; Vomiting; Not interested in what's going on; Unable to get out of bed) specified in the CARIFS questionnaire. Median time was estimated from the Kaplan-Meier curve. Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Time frame: Day 1 up to Day 15

Time to Return to Normal Health and Activity

Time to return to normal health and activity was defined 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?" and remaining so for at least 21.5 hours. Median time was estimated from the Kaplan-Meier curve.Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Time frame: Day 1 up to Day 15

Number of Participants With Influenza-Related Complications

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

Time frame: Day 1 up to Day 29

Number of Participants Requiring Antibiotics

The number of participants who required antibiotics for influenza related complication are reported here.

Time frame: Day 1 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 any study treatment and first time when the influenza virus titer was below the limit of detection (0.75 log10 tissue culture infectious dose (TCID)50/milliliters \[mL\]). Participants whose virus titers did not reach the limit by the last observation time point were treated as censored at that time point. One day was converted into 24 hours. Median time was estimated from the Kaplan-Meier curve.

Time frame: Day 1 up to Day 29

Time to Cessation of Viral Shedding by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)

Time to cessation of viral shedding by RT-PCR, in hours, was defined as the time between the initiation of study treatment and first time when the virus ribonucleic acid (RNA) by RT-PCR qualitative result was negative (no cycle threshold \[Ct\]-value detectable). Participants who did not have a negative result by the last observation time point were treated as censored at that time point. For the participants with multiple virus types, this endpoint was defined as the time between the initiation of the study treatment and first time when the virus RNA by RT-PCR qualitative result was negative for all virus types. One day was converted into 24 hours. Median time was estimated from the Kaplan -Meier curve. Participants with a positive virus RNA on Day 1 are included in this analysis.

Time frame: Day 1 up to Day 29

Change From Baseline in Influenza Virus Titer Over Time

Change from baseline in influenza virus titer (log10TCID50/mL) was defined as the change from baseline in influenza virus titer on Days 2, 4, 6, 10, and 29. If influenza virus titer was less than the lower limit of quantification (LLOQ), the virus titer was imputed as 0.749 (log10TCID50/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 29

Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time

Change from baseline in the amount of virus RNA was defined as the change from baseline in the amount of virus RNA on Days 2, 4, 6 and 10. If the amount of virus RNA is less than the lower limit of quantification, the amount of virus RNA was imputed as the relevant LLOQ (log10 viral particles per mililiter (vp/mL)). If a participant was infected with multiple virus types, the sum of virus RNA (log10 vp/mL) was used for analysis. Participants with a positive virus RNA by RT-PCR on Day 1 were included in this analysis.

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

Percentage of Participants With Positive Influenza Virus Titer Over Time

Percentage of participants positive for influenza virus titer at each visit were defined as the percentage of participants whose influenza virus titer was not less than the LLOQ (0.75 log10TCID50/mL) or positive among those assessed for influenza virus titer on Days 2, 4, 6, 10 and 29. Participants with a positive influenza virus titer on Day 1 were included in this analysis.

Time frame: Baseline, Days 2, 4, 6, 10, and 29

Percentage of Participants Positive by RT-PCR Over Time

Percentage of participants positive by RT-PCR at each visit was defined as the percentage of participants with a positive qualitative result among those assessed by RT-PCR on Days 2, 4, 6, 10 and 29. Participants with a positive RT-PCR result on Day 1 were included in this analysis. Percentages are rounded off.

Time frame: Baseline, Days 2, 4, 6, 10, and 29

Area Under the Concentration-Time Curve (AUC) in Virus Titer

AUC in virus titer was calculated using the trapezoidal method. Twenty-four hours of time was converted into one day. Participants with a positive virus titer on Day 1 were included in this analysis. The LLOQ and lower limit of detection was defined as 0.75 log10TCID50/mL for flu A and 0.75 log10TCID50/mL for flu B. If a participant was infected with multiple virus types, the sum of those virus titers will be used for analysis.

Time frame: Day 1 up to Day 29

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

AUC in virus RNA (RT-PCR) was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR). AUC was calculated using the trapezoidal method similar to AUC in virus titer. Participants with a positive RT-PCR result on Day 1 were subjected to this analysis. If the amount of virus RNA is less than the lower limit of quantification, the amount of virus RNA was imputed as the relevant LLOQ (log10 viral particles per mililiter (vp/mL)). If a participant was infected with multiple virus types, the sum of those the amount of virus RNA was used for analysis.

Time frame: Day 1 up to Day 29