Clinical trial NCT03629184: Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants With Influenza-Like Symptoms
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 173
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 29
Secondary outcomes:
measure: Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population
timeFrame: Days 1 (Post-Dose), 2, 4, 6 and 10
measure: Plasma Concentrations of S-033447 - Sparse PK Population
timeFrame: Days 1 (Post-Dose), 2, 4, 6 and 10
measure: Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population
timeFrame: Days 1 (Post-Dose), 2, 4, 6 and 10
measure: Plasma Concentrations of S-033447 - Extensive PK Population
timeFrame: Days 1 (Post-Dose), 2, 4, 6 and 10
measure: Time to Alleviation of Influenza Signs and Symptoms
timeFrame: Up to Day 15
measure: Duration of Fever
timeFrame: Up to Day 15
measure: Duration of Symptoms
timeFrame: Up to Day 15
measure: Time to Return to Normal Health and Activity
timeFrame: Up to Day 15
measure: Frequency of Influenza-Related Complications
timeFrame: Up to Day 29
measure: Percentage of Participants With Influenza-Related Complications
timeFrame: Up to Day 29
measure: Percentage of Participants Requiring Antibiotics
timeFrame: Up to Day 29
measure: Time to Cessation of Viral Shedding by Virus Titer
timeFrame: Day 1 - Day 29
measure: Time to Cessation of Viral Shedding by RT-PCR
timeFrame: Day 1 - Day 29
measure: Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29
timeFrame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
measure: Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29
timeFrame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
measure: Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10
timeFrame: Baseline, Day 2, 3 (optional), 4, 6, 10
measure: Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29
timeFrame: Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
measure: Area Under the Curve in Virus Titer
timeFrame: Day 1 - Day 29
measure: Area Under the Curve in the Amount of Virus RNA (RT-PCR)
timeFrame: Day 1 - Day 10
measure: Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil
timeFrame: Up to Day 10
measure: Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447.
timeFrame: Up to Day 10
measure: Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil
timeFrame: Up to Day 10
measure: Maximum Plasma Concentration (Cmax) of S-033447
timeFrame: Up to Day 10
measure: Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil
timeFrame: Up to Day 10
measure: Time to Maximum Plasma Concentration (Tmax) of S-033447
timeFrame: Up to Day 10
measure: Plasma Concentrations of Baloxavir Marboxil by Dosage
timeFrame: 24, 72, 96 and 240 hours post-dose
measure: Plasma Concentrations of S-033447 by Dosage
timeFrame: 24, 72, 96 and 240 hours post-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research; Pediatrics
state: Alabama
city: Harrisburg
country: United States
facility: Harrisburg Family Medical Center
state: Arkansas
city: Jonesboro
country: United States
facility: The Children's Clinic of Jonesboro, P.A.
state: Arkansas
city: Los Angeles
country: United States
facility: The Probe Medical Research
state: California
city: Ontario
country: United States
facility: Orange County Research Institute
state: California
city: San Diego
country: United States
facility: Khruz Biotechnology Research Institute
state: California
city: Pensacola
country: United States
facility: Avanza Medical Research Center
state: Florida
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Topeka
country: United States
facility: Cotton O'Neil Clinic; Stormont-Vail Hlth Care
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric Research Center
state: Kentucky
city: Bridgeton
country: United States
facility: Spiegel, Craig
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, Llc
state: Nebraska
city: Las Vegas
country: United States
facility: Machuca Family Medicine
state: Nevada
city: Charlotte
country: United States
facility: OnSite Clinical Solutions LLC
state: North Carolina
city: Smithfield
country: United States
facility: Montgomery Medical Research /Frontier Clinical Research
state: North Carolina
city: Dayton
country: United States
facility: Ohio Pediatric Research Association
state: Ohio
city: Charleston
country: United States
facility: Coastal Pediatric Research
state: South Carolina
city: Cleveland
country: United States
facility: AFC Urgent Care- Cleveland
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Dallas
country: United States
facility: Oak Cliff Research Company, LLC
state: Texas
city: Houston
country: United States
facility: HD Research Corp
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Tekton Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials
state: Texas
city: Salt Lake City
country: United States
facility: FirstMed East (J Lewis Research)
state: Utah
city: Salt Lake City
country: United States
facility: Advanced Clinical Research - Jordan Ridge Family Medicine
state: Utah
city: San Jose
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Petach Tikva
country: Israel
facility: Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic
city: Monterrey, N.L
country: Mexico
facility: Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Debica
country: Poland
facility: Prywatny Gabinet Lekarski
city: Siemianowice Śląskie
country: Poland
facility: NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska
city: Samara
country: Russian Federation
facility: MC Gepatolog
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría
state: LA Coruña
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Pediatria
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Baker J, Block SL, Matharu B, Burleigh Macutkiewicz L, Wildum S, Dimonaco S, Collinson N, Clinch B, Piedra PA. Baloxavir Marboxil Single-dose Treatment in Influenza-infected Children: A Randomized, Double-blind, Active Controlled Phase 3 Safety and Efficacy Trial (miniSTONE-2). Pediatr Infect Dis J. 2020 Aug;39(8):700-705. doi: 10.1097/INF.0000000000002747.