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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03629184
• Other study ID #: CP40563
• Secondary ID: 2018-002169-21
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2018
• Est. completion date: April 3, 2019

Study information

• Verified date: April 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 173
• Est. completion date: April 3, 2019
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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.
• 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.

Locations

Country	Name	City	State
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San Jose
Israel	Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic	Petach Tikva
Mexico	Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey	Monterrey, N.L
Poland	NZOZ Vitamed	Bydgoszcz
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddzial Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz
Poland	Prywatny Gabinet Lekarski	Debica
Poland	NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska	Siemianowice Slaskie
Russian Federation	MC Gepatolog	Samara
Spain	Hospital Universitario 12 de Octubre; Servicio de Pediatria	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría	Santiago de Compostela	LA Coruña
United States	Kentucky Pediatric Research Center	Bardstown	Kentucky
United States	Central Alabama Research; Pediatrics	Birmingham	Alabama
United States	Spiegel, Craig	Bridgeton	Missouri
United States	Coastal Pediatric Research	Charleston	South Carolina
United States	OnSite Clinical Solutions LLC	Charlotte	North Carolina
United States	AFC Urgent Care- Cleveland	Cleveland	Tennessee
United States	Oak Cliff Research Company, LLC	Dallas	Texas
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Harrisburg Family Medical Center	Harrisburg	Arkansas
United States	HD Research Corp	Houston	Texas
United States	Mercury Clinical Research	Houston	Texas
United States	Clinical Research Prime	Idaho Falls	Idaho
United States	The Children's Clinic of Jonesboro, P.A.	Jonesboro	Arkansas
United States	Holston Medical Group	Kingsport	Tennessee
United States	Machuca Family Medicine	Las Vegas	Nevada
United States	The Probe Medical Research	Los Angeles	California
United States	Meridian Clinical Research, Llc	Omaha	Nebraska
United States	Orange County Research Institute	Ontario	California
United States	Avanza Medical Research Center	Pensacola	Florida
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	Tekton Research	San Antonio	Texas
United States	Khruz Biotechnology Research Institute	San Diego	California
United States	Montgomery Medical Research /Frontier Clinical Research	Smithfield	North Carolina
United States	DM Clinical Research	Tomball	Texas
United States	Cotton O'Neil Clinic; Stormont-Vail Hlth Care	Topeka	Kansas
United States	ClinPoint Trials	Waxahachie	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Costa Rica,  Israel,  Mexico,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to Day 29
Secondary	Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population	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.	Days 1 (Post-Dose), 2, 4, 6 and 10
Secondary	Plasma Concentrations of S-033447 - Sparse PK Population	Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.	Days 1 (Post-Dose), 2, 4, 6 and 10
Secondary	Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population	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.	Days 1 (Post-Dose), 2, 4, 6 and 10
Secondary	Plasma Concentrations of S-033447 - Extensive PK Population	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.	Days 1 (Post-Dose), 2, 4, 6 and 10
Secondary	Time to Alleviation of Influenza Signs and Symptoms	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])	Up to Day 15
Secondary	Duration of Fever	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.	Up to Day 15
Secondary	Duration of Symptoms	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.	Up to Day 15
Secondary	Time to Return to Normal Health and Activity	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?"	Up to Day 15
Secondary	Frequency of Influenza-Related Complications	Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.	Up to Day 29
Secondary	Percentage of Participants With Influenza-Related Complications	Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.	Up to Day 29
Secondary	Percentage of Participants Requiring Antibiotics		Up to Day 29
Secondary	Time to Cessation of Viral Shedding by Virus Titer	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.	Day 1 - Day 29
Secondary	Time to Cessation of Viral Shedding by RT-PCR	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.	Day 1 - Day 29
Secondary	Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 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.	Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
Secondary	Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 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)	Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
Secondary	Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10		Baseline, Day 2, 3 (optional), 4, 6, 10
Secondary	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
Secondary	Area Under the Curve in Virus Titer	Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.	Day 1 - Day 29
Secondary	Area Under the Curve in the Amount of Virus RNA (RT-PCR)	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.	Day 1 - Day 10
Secondary	Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil	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.	Up to Day 10
Secondary	Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447.	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.	Up to Day 10
Secondary	Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil	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.	Up to Day 10
Secondary	Maximum Plasma Concentration (Cmax) of S-033447	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.	Up to Day 10
Secondary	Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil	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.	Up to Day 10
Secondary	Time to Maximum Plasma Concentration (Tmax) of S-033447	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.	Up to Day 10
Secondary	Plasma Concentrations of Baloxavir Marboxil by Dosage	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, 72, 96 and 240 hours post-dose
Secondary	Plasma Concentrations of S-033447 by Dosage	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, 72, 96 and 240 hours post-dose