E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Influenza is a viral infection that is highly contagious and attacks the respiratory system including the nose, throat and lungs. It is commonly called the flu. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022001 |
E.1.2 | Term | Influenza (epidemic) |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022003 |
E.1.2 | Term | Influenza B virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022002 |
E.1.2 | Term | Influenza A virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016790 |
E.1.2 | Term | Flu |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the safety of a single dose of baloxavir marboxil
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of baloxavir marboxil • To evaluate the virological activity of baloxavir marboxil • To evaluate the pharmacokinetics (PK) of baloxavir marboxil after single dose administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age from birth to < 1 year at screening - Parent/guardian willing and able to comply with study requirements, in the investigator’s judgment - Patients with a diagnosis of influenza virus infection confirmed by the presence of all of the following: o In the investigator's judgement there is a clinical suspicion of influenza o At least one respiratory symptom (either cough or coryza) o Positive prescreening influenza test (Rapid Influenza Diagnostic Test or polymerase chain reaction [PCR]) performed within 48 hours of screening Results from local testing as part of standard of care are acceptable if samples are collected within 48 hours of screening and recorded in the patients' medical records. -Patients with a negative prescreening COVID-19 test (RAT or PCR) performed within 48 hours of screening Results from local testing as part of standard of care are acceptable if samples are collected within 48 hours of screening and recorded in the patients' medical records -The time interval between the onset of symptoms and screening is <= 96 hours
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E.4 | Principal exclusion criteria |
- Hospitalized for complications of influenza or significant comorbidities o Patients hospitalized for observation, monitoring or precautionary supportive care may still be acceptable for enrollment provided all eligibility criteria are met. - 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) - Weigh < 2.5 kg at screening o Only children > 4.5 kg will be eligible to take part in countries that have volume limits for blood draws set at 1% of the total blood volume (maximum over 24 hour period) and 3% of the total blood volume (maximum over 30-day period) - 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, hepatitis, cirrhosis, or pulmonary disease or patients with known chronic renal failure - Active cancer at any site - History of organ transplant - Known hypersensitivity to study drug (i.e. baloxavir marboxil) or the drug excipients - Known hypersensitivity 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
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence, severity, and timing of adverse events, serious adverse events, vital sign measurements, and clinical laboratory tests
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to Day 29 or early termination
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E.5.2 | Secondary end point(s) |
1. Time to alleviation of influenza signs and symptoms 2. Duration of fever 3. Duration of symptoms 4. Time to return to normal health and activity 5. Frequency of influenza-related complications 6. Proportion of patients requiring antibiotics 7. Time to cessation of viral shedding by virus titer and by reverse transcription-polymerase chain reaction (RT PCR) 8. Change from baseline in influenza virus titer and in the amount of virus RNA (RT-PCR) at each time point 9. Proportion of patients with positive influenza virus titer and proportion of patients positive by RT-PCR at each time point 10. Area under the curve in virus titer and in the amount of virus RNA (RT-PCR) 11. Plasma concentrations of baloxavir marboxil (pro drug) and S-033447 (active metabolite) will be summarized by time C24 (plasma concentration 24 hours postdose) and C72 (plasma concentration 72 hours postdose) and cohort 12. Population PK model derived PK parameters (e.g., apparent clearance [CL/F], apparent volume of distribution for the central compartment [Vc/F], area under the concentration–time curve from time 0 to infinity [AUCinf], maximum plasma concentration [Cmax])
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. Up to Day 15 5-7. Up to Day 29 8. From baseline (Day 1) to Day 29 9-10. Up to Day 29 11. 24 and 72 hours post dose of study drug 12. Day 1, Day 2, Day 4, Day 6-10
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Costa Rica |
Israel |
Mexico |
Panama |
South Africa |
Thailand |
United States |
Finland |
Poland |
Spain |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |