Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants With Influenza-Like Symptoms
- Registration Number
- NCT03629184
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 173
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Baloxavir Marboxil 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. Oseltamivir 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
- Primary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) 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
Name Time Method Plasma Concentrations of S-033447 - Extensive PK Population 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.
Plasma Concentrations of S-033447 - Sparse PK Population Days 1 (Post-Dose), 2, 4, 6 and 10 Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.
Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population 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.
Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447. 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.
Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil 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.
Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population 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.
Time to Alleviation of Influenza Signs and Symptoms 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 \[°C\])Frequency of Influenza-Related Complications Up to Day 29 Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time to Cessation of Viral Shedding by Virus Titer 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.
Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 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.
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 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)
Duration of Fever 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.
Duration of Symptoms 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.
Time to Return to Normal Health and Activity 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?"
Percentage of Participants With Influenza-Related Complications Up to Day 29 Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time to Cessation of Viral Shedding by RT-PCR 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.
Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 Baseline, Day 2, 3 (optional), 4, 6, 10 Maximum Plasma Concentration (Cmax) of S-033447 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.
Percentage of Participants Requiring Antibiotics Up to Day 29 Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29 Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil 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.
Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil 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.
Time to Maximum Plasma Concentration (Tmax) of S-033447 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.
Plasma Concentrations of Baloxavir Marboxil by Dosage 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.
Area Under the Curve in Virus Titer Day 1 - Day 29 Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.
Area Under the Curve in the Amount of Virus RNA (RT-PCR) 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.
Plasma Concentrations of S-033447 by Dosage 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.
Trial Locations
- Locations (37)
The Probe Medical Research
🇺🇸Los Angeles, California, United States
Kentucky Pediatric Research Center
🇺🇸Bardstown, Kentucky, United States
Orange County Research Institute
🇺🇸Ontario, California, United States
OnSite Clinical Solutions LLC
🇺🇸Charlotte, North Carolina, United States
Khruz Biotechnology Research Institute
🇺🇸San Diego, California, United States
Oak Cliff Research Company, LLC
🇺🇸Dallas, Texas, United States
Spiegel, Craig
🇺🇸Bridgeton, Missouri, United States
Ohio Pediatric Research Association
🇺🇸Dayton, Ohio, United States
DM Clinical Research
🇺🇸Tomball, Texas, United States
Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
🇪🇸Santiago de Compostela, LA Coruña, Spain
HD Research Corp
🇺🇸Houston, Texas, United States
Hospital Universitario 12 de Octubre; Servicio de Pediatria
🇪🇸Madrid, Spain
Central Alabama Research; Pediatrics
🇺🇸Birmingham, Alabama, United States
Avanza Medical Research Center
🇺🇸Pensacola, Florida, United States
Cotton O'Neil Clinic; Stormont-Vail Hlth Care
🇺🇸Topeka, Kansas, United States
Meridian Clinical Research, Llc
🇺🇸Omaha, Nebraska, United States
Montgomery Medical Research /Frontier Clinical Research
🇺🇸Smithfield, North Carolina, United States
Harrisburg Family Medical Center
🇺🇸Harrisburg, Arkansas, United States
Coastal Pediatric Research
🇺🇸Charleston, South Carolina, United States
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
Clinical Research Prime
🇺🇸Idaho Falls, Idaho, United States
Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii
🇵🇱Bydgoszcz, Poland
The Children's Clinic of Jonesboro, P.A.
🇺🇸Jonesboro, Arkansas, United States
ICIMED Instituto de Investigación en Ciencias Médicas
🇨🇷San Jose, Costa Rica
AFC Urgent Care- Cleveland
🇺🇸Cleveland, Tennessee, United States
Machuca Family Medicine
🇺🇸Las Vegas, Nevada, United States
Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic
🇮🇱Petach Tikva, Israel
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey
🇲🇽Monterrey, N.L, Mexico
Prywatny Gabinet Lekarski
🇵🇱Debica, Poland
NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska
🇵🇱Siemianowice Śląskie, Poland
MC Gepatolog
🇷🇺Samara, Russian Federation
Tekton Research
🇺🇸San Antonio, Texas, United States
Advanced Clinical Research - Jordan Ridge Family Medicine
🇺🇸Salt Lake City, Utah, United States
FirstMed East (J Lewis Research)
🇺🇸Salt Lake City, Utah, United States
Mercury Clinical Research
🇺🇸Houston, Texas, United States
ClinPoint Trials
🇺🇸Waxahachie, Texas, United States