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Completed

NCT Number: NCT03629184

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

This study will evaluate the safety, pharmacokinetics, and efficacy of baloxavir marboxil compared with oseltamivir in a single influenza episode in otherwise healthy pediatric participants (i.e., 1 to <12 years of age) with influenza-like symptoms.

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Key information

Conditions

Influenza Infections Influenza, Human Orthomyxoviridae Infections RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

1 year–11 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

ICIMED Instituto de Investigación en Ciencias Médicas, San José, Costa Rica

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Aged 1 to < 12 years at randomization (Day 1).
  • Written informed consent/assent for study participation obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the patient's level of understanding
  • Participant able to comply with study requirements, depending on the patient's level of understanding
  • Participant with a diagnosis of influenza virus infection confirmed by the presence of all of the following:
  • Fever ≥ 38 degree celsius (tympanic temperature) at screening
  • At least one respiratory symptom (either cough or nasal congestion)
  • The time interval between the onset of symptoms and screening is ≤ 48 hours

Exclusion criteria

  • Severe symptoms of influenza virus infection requiring inpatient treatment
  • Concurrent infections requiring systemic antiviral therapy at screening
  • Require, in the opinion of the investigator, any of the prohibited medication during the study
  • Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening
  • Immunization with a live/attenuated influenza vaccine in the 2 weeks prior to randomization
  • 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 transplantation
  • Known allergy to either study drug (i.e., baloxavir marboxil and oseltamivir) or to acetaminophen
  • Females with child-bearing potential
  • Participation in a clinical trial within 4 weeks or five half-lives of exposure to an investigational drug prior to screening, whichever is longer

Treatment and study plan

Baloxavir Marboxil

Drug

Baloxavir marboxil will be administered as oral suspension in a single dose on Day 1.

Oseltamivir matching placebo will also be administered as oral suspension twice daily (BID) for 5 days.

oseltamivir

Drug

Oseltamivir will be administered as oral suspension BID for 5 days. Participants receiving oseltamivir will also receive baloxavir marboxil matching placebo as oral suspension, single dose on Day 1.

Primary outcomes

  1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Up to Day 29

    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 outcomes

  1. Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population

    Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

    Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

  2. Plasma Concentrations of S-033447 - Sparse PK Population

    Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

    Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.

  3. Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population

    Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

    Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

  4. Plasma Concentrations of S-033447 - Extensive PK Population

    Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10

    Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.

  5. Time to Alleviation of Influenza Signs and Symptoms

    Time frame: Up to Day 15

    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])

  6. Duration of Fever

    Time frame: Up 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.

  7. Duration of Symptoms

    Time frame: Up to Day 15

    The clinical 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.

  8. Time to Return to Normal Health and Activity

    Time frame: Up to Day 15

    Time to Return to Normal health and activity' is identified 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?"

  9. Frequency of Influenza-Related Complications

    Time frame: Up to Day 29

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

  10. Percentage of Participants With Influenza-Related Complications

    Time frame: Up to Day 29

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

  11. Percentage of Participants Requiring Antibiotics

    Time frame: Up to Day 29

  12. Time to Cessation of Viral Shedding by Virus Titer

    Time frame: Day 1 - Day 29

    Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of any study treatment and first time when the influenza virus titer is below the limit of detection.

  13. Time to Cessation of Viral Shedding by RT-PCR

    Time frame: Day 1 - Day 29

    Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection.

  14. Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29

    Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

    Influenza virus titer (log10TCID50/ML) is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.

  15. Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29

    Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

    If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)

  16. Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10

    Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10

  17. Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29

    Time frame: Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29

  18. Area Under the Curve in Virus Titer

    Time frame: Day 1 - Day 29

    Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.

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

    Time frame: Day 1 - Day 10

    AUC in virus RNA (RT-PCR) is defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 10. AUC is calculated using the trapezoidal method similar to AUC in virus titer.

  20. Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  21. Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447.

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  22. Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  23. Maximum Plasma Concentration (Cmax) of S-033447

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  24. Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  25. Time to Maximum Plasma Concentration (Tmax) of S-033447

    Time frame: Up to Day 10

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  26. Plasma Concentrations of Baloxavir Marboxil by Dosage

    Time frame: 24, 72, 96 and 240 hours post-dose

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

  27. Plasma Concentrations of S-033447 by Dosage

    Time frame: 24, 72, 96 and 240 hours post-dose

    Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects <20 kgs and 40 mg dose was used for subjects >20 kgs.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Active (Oseltamivir)-Controlled Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Otherwise Healthy Pediatric Patients 1 to <12 Years of Age With Influenza-Like Symptoms

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Aug 14, 2018
Registry last updated
Apr 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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