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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03629184
Recruitment Status : Completed
First Posted : August 14, 2018
Results First Posted : April 29, 2020
Last Update Posted : April 29, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Influenza Drug: Baloxavir Marboxil Drug: Oseltamivir Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 173 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : November 20, 2018
Actual Primary Completion Date : April 3, 2019
Actual Study Completion Date : April 3, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot
Drug Information available for: Oseltamivir

Arm Intervention/treatment
Experimental: Baloxavir Marboxil
Participants will receive a single oral dose of baloxavir marboxil on Day 1 (based on body weight). Oseltamivir matching placebo will also be administered orally twice daily (BID) for 5 days.
Drug: Baloxavir Marboxil

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.


Active Comparator: Oseltamivir
Participants will receive oseltamivir orally BID for 5 days (based on body weight). Baloxavir marboxil matching placebo will also be administered orally on Day 1
Drug: Oseltamivir
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 Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03629184


Locations
Show Show 37 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] June 29, 2018
Statistical Analysis Plan  [PDF] May 24, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03629184    
Other Study ID Numbers: CP40563
2018-002169-21 ( EudraCT Number )
First Posted: August 14, 2018    Key Record Dates
Results First Posted: April 29, 2020
Last Update Posted: April 29, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Baloxavir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action