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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03653364

Collaborator

(none)

Enrollment

Locations

Arm

54.2

Anticipated Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Baloxavir Marboxil	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 23, 2019

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baloxavir Marboxil Participants will receive single oral dose of baloxavir marboxil on Day 1 (based on body weight and age).	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

Arm

Intervention/Treatment

Experimental: Baloxavir Marboxil

Participants will receive single oral dose of baloxavir marboxil on Day 1 (based on body weight and age).

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

Outcome Measures

Primary Outcome Measures

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

Plasma Concentrations of Baloxavir Marboxil and S-033447 [Day 2 and Day 4]
Area Under the Concentration to Time Curve from Time 0 to Infinity (AUC0-inf) of baloxavir marboxil and S-033447 [Up to Day 10]
Maximum Plasma Concentration (Cmax) of baloxavir marboxil and S-033447 [Up to Day 10]
Time to Maximum Plasma Concentration (Tmax) of baloxavir marboxil and S-033447 [Up to Day 10]
Apparent Half-Life (T1/2) of baloxavir marboxil and S-033447 [Up to Day 10]
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])
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 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]
Frequency of Influenza-Related Complications [Up to Day 29]
The influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Percentage of Participants Requiring Antibiotics [Up to Day 29]
Time to Cessation of Viral Shedding by Virus Titer and by RT-PCR [Day 1 - Day 29]
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]
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]
Area Under the Curve in Virus Titer and in the Amount of Virus RNA (RT-PCR) [Day 1 - Day 29]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uni of Alabama At Birmingham; Departement of Medicine	Birmingham	Alabama	United States	35233
2	The Children's Clinic of Jonesboro, P.A.	Jonesboro	Arkansas	United States	72401
3	Khruz Biotechnology Research Institute	San Diego	California	United States	92102
4	University of Colorado Denver, Children's Hospital	Aurora	Colorado	United States	80045
5	Avanza Medical Research Center	Pensacola	Florida	United States	32503
6	Usf Health	Tampa	Florida	United States	33606
7	Clinical Research Prime	Idaho Falls	Idaho	United States	83404
8	Ann & Robert H. Lurie Children's Hospital of Chicago;Division of Infectious Disease	Chicago	Illinois	United States	60611
9	Kentucky Pediatric Research Center	Bardstown	Kentucky	United States	40004
10	Children's Minnesota	Minneapolis	Minnesota	United States	55404
11	Midwest Childrens Health Research Institute	Lincoln	Nebraska	United States	68516
12	SUNY Upstate Medical University	Syracuse	New York	United States	13210
13	OnSite Clinical Solutions LLC	Charlotte	North Carolina	United States	28203
14	Coastal Pediatric Research	Charleston	South Carolina	United States	29414
15	Oak Cliff Research Company, LLC	Dallas	Texas	United States	75218
16	HD Research Corp	Houston	Texas	United States	77004
17	Mercury Clinical Research	Houston	Texas	United States	77036-3316
18	Tekton Research	San Antonio	Texas	United States	78229
19	DM Clinical Research	Tomball	Texas	United States	77375
20	Clear Lake Pediatric Centre; Tranquility Clinical Research	Webster	Texas	United States	77598
21	ICIMED Instituto de Investigación en Ciencias Médicas	San José		Costa Rica	10108
22	Helsingin yliopistollinen keskussairaala; Uusi Lastensairaala	Helsinki		Finland	00029 HUS
23	TAYS Lastenklinikka; Lasten lääketutkimuskeskus Peetu	Tampere		Finland	33520
24	Turun Yliopistollinen keskussairaala; Lasten ja nuorten klinikka	Turku		Finland	20520
25	Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic	Petach Tikva		Israel	4931807
26	Hospital Infantil de Mexico; Infectology	Mexico City		Mexico	06720
27	Policentro de Salud de Juan Diaz	Panama		Panama	0816-06812
28	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz		Poland	85-030
29	IN VIVO Sp. z o.o.	Bydgoszcz		Poland	85-048
30	NZOZ Vitamed	Bydgoszcz		Poland	85-079
31	Prywatny Gabinet Lekarski	Debica		Poland	39-200
32	NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska	Siemianowice Śląskie		Poland	41-103
33	Samodzielny Zespol Publicznych Zakladow Opieki Zdrowotnej im. Dzieci Warszawy w Dziekanowie Lesnym	Łomianki		Poland	05-092
34	NZOZ Salmed	Łęczna		Poland	21-010
35	The scientific-research institute of epidemiology; Infectious clinical hospital №2 of Moscow H.D.	Moskva	Moskovskaja Oblast	Russian Federation	111123
36	LCS Clinical Research Unit; Clinical Research	Cosmo CITY		South Africa	2188
37	Global Clinical Trials; Clinical Trials	Gauteng		South Africa	0001
38	GAMA; Clinical Research	Germiston		South Africa	1401
39	Peermed Clinical Trial Centre	Kempton Park		South Africa	1619
40	Metropolitan Clinical Research Institute	Polokwane		South Africa	0699
41	Pholosho Netcare; Netcare Hospital	Polokwane		South Africa	0699
42	Setshaba Research Centre; Clinical Research	Pretoria		South Africa	0152
43	Clinix Botshelong; Empilweni Private Hospital	Vosloorus EXT 9		South Africa	1475
44	Clinical Projects Research SA pty Ltd	Worcester		South Africa	6850
45	Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría	Santiago de Compostela	LA Coruña	Spain	15706
46	Hospital Universitario 12 de Octubre; Servicio de Pediatria	Madrid		Spain	28041
47	Queen Sirikit National Institute of Child Health (Children's Hospital); Pediatrics	Payathai		Thailand	10400

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT03653364

Other Study ID Numbers:

CP40559
2018-002154-70

First Posted:

Aug 31, 2018

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Influenza, Human

Baloxavir

Study Results

No Results Posted as of Aug 22, 2022