Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms

Influenza Clinical Trial

Official title:

A Multicenter, Single-Arm, Open-Label Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Otherwise Healthy Pediatric Patients From Birth to < 1 Year With Influenza-Like Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03653364
• Other study ID #: CP40559
• Secondary ID: 2018-002154-70
• Status: Completed
• Phase: Phase 3
• Start date: January 23, 2019
• Est. completion date: April 3, 2023

Study information

• Verified date: August 2023
• 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 in healthy pediatric participants from birth to <1 year with influenza like symptoms

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 3, 2023
• Est. primary completion date: April 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Year

Eligibility

Inclusion Criteria:

• Age from birth to < 1 year at screening
• Written informed consent for study participation obtained from participant's parents or legal guardian
• Parent/guardian willing and able to comply with study requirements, in the investigator's judgment
• Participants with a diagnosis of influenza virus infection confirmed by the presence

of all of the following:

1. In the investigator's judgement there is a clinical suspicion of influenza

2. At least one respiratory symptom (either cough or coryza) (b) Positive prescreening influenza test (RIDT or PCR) performed within 48 hours of screening

• Participants with a negative prescreening COVID-19 test (RAT or PCR) within 48 hours of screening
• The time interval between the onset of symptoms and screening is = 96 hours (the onset of symptoms is defined as the time when body temperature first exceeded 37.5°C if known, or the time when the first symptom was noticed by the parent or caregiver)

Exclusion Criteria:

• Hospitalized for complications of influenza or significant comorbidities
• Concurrent infections requiring systemic antiviral therapy at screening
• Require, in the opinion of the investigator, any of the prohibited medication during the study
• Preterm neonates (born at < 37 weeks gestation) and/or weighing < 2.5 kg at screening
• Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening
• Immunization with a live/attenuated influenza vaccine during the 2 weeks prior to screening
• 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 transplant
• Known hypersensitivity to study drug (i.e., baloxavir marboxil) or to acetaminophen
• 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
Participants will receive single oral dose of baloxavir marboxil on Day 1 based on body weight and age. Participants will be recruited in parallel to the following three cohorts: Cohort I: = 3 months to < 12 months old (minimum 8 participants): 2 mg/kg Cohort II: = 4 weeks to < 3 months old (minimum 4 patients): 1 mg/kg Cohort III: birth to < 4 weeks old (minimum 4 patients): 1 mg/kg

Locations

Country	Name	City	State
Bulgaria	MHAT Stamen Iliev AD	Montana
Bulgaria	SHAT for Pneumo-Phtysiatric Diseases ?Dr. Dimitar Gramatikov?; Dept. of Pulmonology and Phtisiatrics	Ruse
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
Finland	TAYS Lastenklinikka; Lasten lääketutkimuskeskus Peetu	Tampere
Israel	Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic	Petach Tikva
Mexico	Hospital Infantil de Mexico; Infectology	Mexico City	Mexico CITY (federal District)
Poland	NZOZ Salmed	??czna
Poland	Samodzielny Zespol Publicznych Zakladow Opieki Zdrowotnej im. Dzieci Warszawy w Dziekanowie Lesnym	?omianki
Poland	IN VIVO Sp. z o.o.	Bydgoszcz
Poland	NZOZ Vitamed	Bydgoszcz
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddzia? Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz
Russian Federation	The scientific-research institute of epidemiology; Infectious clinical hospital ?2 of Moscow H.D.	Moskva	Moskovskaja Oblast
South Africa	Global Clinical Trials; Clinical Trials	Gauteng
South Africa	GAMA; Clinical Research	Germiston
South Africa	Peermed Clinical Trial Centre	Kempton Park
South Africa	Metropolitan Clinical Research Institute	Polokwane
South Africa	Pholosho Netcare; Netcare Hospital	Polokwane
South Africa	Setshaba Research Centre; Clinical Research	Pretoria
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	Ann & Robert H. Lurie Children's Hospital of Chicago;Division of Infectious Disease	Chicago	Illinois
United States	Oak Cliff Research Company, LLC	Dallas	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	Tekton Research	San Antonio	Texas
United States	Usf Health	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Bulgaria,  Costa Rica,  Finland,  Israel,  Mexico,  Poland,  Russian Federation,  South Africa,  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 and S-033447		Day 2 and Day 4
Secondary	Area Under the Concentration to Time Curve from Time 0 to Infinity (AUC0-inf) of baloxavir marboxil and S-033447		Up to Day 10
Secondary	Maximum Plasma Concentration (Cmax) of baloxavir marboxil and S-033447		Up to Day 10
Secondary	Time to Maximum Plasma Concentration (Tmax) of baloxavir marboxil and S-033447		Up to Day 10
Secondary	Apparent Half-Life (T1/2) of baloxavir marboxil and S-033447		Up to Day 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 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		Up to Day 15
Secondary	Frequency of Influenza-Related Complications	The 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 and by RT-PCR		Day 1 - Day 29
Secondary	Change from Baseline in Influenza Virus Titer and in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29		Baseline, Day 2, 4, 6, 10, 15, 29
Secondary	Percentage of Participants with Positive Influenza Virus Titer and Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29		Day 2, 4, 6, 10, 15, 29
Secondary	Area Under the Curve in Virus Titer and in the Amount of Virus RNA (RT-PCR)		Day 1 - Day 29