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

• ClinicalTrials.gov Identifier: NCT03653364
• Recruitment Status: Recruiting
• First Posted: August 31, 2018
• Last Update Posted: December 6, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

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 (Clinical Trial)
• Estimated Enrollment: 30 participants
• 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: January 23, 2019
• Estimated Primary Completion Date: September 2, 2020
• Estimated Study Completion Date: September 2, 2020

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 :

1. Plasma Concentrations of Baloxavir Marboxil and S-033447 [ Time Frame: Day 2 and Day 4 ]
2. Area Under the Concentration to Time Curve from Time 0 to Infinity (AUC0-inf) of baloxavir marboxil and S-033447 [ Time Frame: Up to Day 10 ]
3. Maximum Plasma Concentration (Cmax) of baloxavir marboxil and S-033447 [ Time Frame: Up to Day 10 ]
4. Time to Maximum Plasma Concentration (Tmax) of baloxavir marboxil and S-033447 [ Time Frame: Up to Day 10 ]
5. Apparent Half-Life (T1/2) of baloxavir marboxil and S-033447 [ Time Frame: Up to Day 10 ]
6. Time to Alleviation of Influenza Signs and Symptoms [ Time Frame: 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])
7. Duration of Fever [ Time Frame: 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.
8. Duration of Symptoms [ Time Frame: 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).
9. Time to Return to Normal Health and Activity [ Time Frame: Up to Day 15 ]
10. Frequency of Influenza-Related Complications [ Time Frame: Up to Day 29 ]
    The influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
11. Percentage of Participants Requiring Antibiotics [ Time Frame: Up to Day 29 ]
12. Time to Cessation of Viral Shedding by Virus Titer and by RT-PCR [ Time Frame: Day 1 - Day 29 ]
13. Change from Baseline in Influenza Virus Titer and in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 [ Time Frame: Baseline, Day 2, 4, 6, 10, 15, 29 ]
14. Percentage of Participants with Positive Influenza Virus Titer and Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 [ Time Frame: Day 2, 4, 6, 10, 15, 29 ]
15. Area Under the Curve in Virus Titer and in the Amount of Virus RNA (RT-PCR) [ Time Frame: Day 1 - Day 29 ]

Eligibility Criteria

• Ages Eligible for Study: up to 1 Year (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:
• Fever ≥ 38°C (tympanic temperature) at screening
• At least one respiratory symptom (either cough or coryza)
• 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

Contacts

Contact: Reference Study ID Number: CP40559 www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

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Sponsors and Collaborators

Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03653364 History of Changes
• Other Study ID Numbers: CP40559; 2018-002154-70 ( EudraCT Number )
• First Posted: August 31, 2018
• Last Update Posted: December 6, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Baloxavir; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action