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 commonly known as flu, is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs |
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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 efficacy of a single, oral dose of baloxavir marboxil compared with placebo to prevent secondary within-household transmission of influenza A or B |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of a single, oral dose of baloxavir marboxil compared with placebo to prevent transmission of influenza A or B beyond secondary within-household transmission
• To evaluate the safety and tolerability of a single, oral dose of baloxavir marboxil compared with placebo
• To evaluate index patients treated with baloxavir marboxil compared with those receiving placebo with respect to health status utility measures
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Index Patient(s) (IP or IPs) will be screened first at the site whereas Household Contact(s) (HHC or HHCs) will be screened at the home or site after randomization. HHCs must be enrolled within 24 hours of IP randomization. No HHC will be enrolled before all HHCs have been screened. HHCs can enroll to complete screening only (HHC inclusion criteria part 1) or they can enroll to participate in the full study (HHC inclusion criteria part 1 and part 2).
- Age >=5 and <=64 years
- Able to comply with the study protocol per investigator judgment
- Diagnosed with acute influenza infection by investigator
- Polymerase chain reaction [PCR] (+) or Rapid Influenza Diagnostic Test [RIDT] (+) for influenza A/B based local laboratory results
- PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 Assay or other point-of-care / local laboratory result
- Presence of (a) fever or (b) any influenza symptoms
- The time interval between the onset of fever or influenza symptoms and the pre-dose examinations is ≤48 hours or less
- IP lives in a household where:
o No HHC is known to have been diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional (HCP) in the past 4 weeks
o All HHCs are expected to meet the HHC inclusion criterion 1
o ≥2 HHCs are expected to participate in the full study who have not received the influenza vaccine within 6 months prior to screening
- Women of childbearing potential agree to remain abstinent or use contraceptive measures
Household Contact (HHC) inclusion criteria
1. All HHC living in the home at any time during the study must meet the following criteria
- PCR (-) or RIDT (-) based on local laboratory result
- PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 Assay or other POC / local laboratory result
- HHC lives with no HHC who will be present in the home at any time during the study and who meets any HHC exclusion criteria
- HHC lives with no HHC who does not meet HHC inclusion criterion 1
- HHC lives in a household where ≥2 HHCs meet all of the following:
o a) Start screening within 24 hours post IP randomization.
o b) Have NOT received the influenza vaccine within 6 months prior to screening.
o c) Fulfill full study HHC inclusion criterion 2
2. Each HHC intended for full study must meet the following additional criteria for study entry
- Agree to participate in the full study
- Able to comply with the study protocol per investigator judgment
- No influenza symptoms within 7 days prior to screening; mild symptoms allowed if due to pre-existing condition (e.g. allergies)
- Tympanic temperature <38°C at screening
- Will reside in the IP’s house for at least 7 of the next 9 days and will be present for scheduled study visits
- Willing/able to measure/record temperature, or have another household member perform the task on his/her behalf. Furthermore, a responsible adult will assume responsibility to oversee or perform this task on behalf of minors
- Has not been diagnosed with influenza or taken antivirals for influenza ≤6 months prior to screening
- Does not have moderate or worse active infections OR taking systemic or an internally administered anti -biotic/ -viral/ -fungal
- HHC lives in a household where:
o No HHC has been diagnosed with influenza by an HCP
o All HHCs meet the HHC inclusion criteria required for “All HHC living in the home at any time during the study” and none of the HHC exclusion criteria
o ≥2 HHCs have not received the influenza vaccine ≤6 months prior to screening agree to participate in the full study
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E.4 | Principal exclusion criteria |
IPs exclusion criteria
- IP with severe influenza virus infection requiring inpatient treatment
- IP judged by the investigator to be at high risk for complications of influenza, after consideration of the following or other potential risk factors:
o Women who are pregnant or within 2 weeks post-partum;
o Chronic respiratory diseases including chronic obstructive pulmonary disorder current asthma and cystic fibrosis;
o Neurological and neurodevelopmental disorders, heart disease, blood disorders, endocrine disorders, kidney disorders, liver disorders, metabolic disorders, or morbid obesity;
o Compromised immune system due to disease or medications;
o People younger than 19 years of age on long-term aspirin- or salicylate-containing medications;
o American Indians or Alaska Natives;
o People who live in nursing homes and other long-term care facilities
- IP is >= 12 years old and unable to swallow tablets
- Women who are breastfeeding or have positive pregnancy test at pre-dose screening (unless exempted due to postmenopausal status or surgically sterile or <12 years old and pre-menarcheal).
- IP weighing <40 kg
- IP with concurrent (non-influenza) infections requiring systemic anti -microbial / -viral therapy at the pre-dose examinations
- IP who has received an investigational monoclonal antibody for a viral disease in the last year
- IP who has received an investigational therapy within 30 days or 5 drug-elimination half-lives, whichever is longer, prior to screening
- IP lives with an HCC who, based on available information meets the HHC exclusion criteria
- Known hypersensitivity to baloxavir marboxil or the drug product excipients
- Any other contraindication for treatment with baloxavir marboxil as deemed by the treating physician or Principal Investigator
- IP previously included in the study
HHC exclusion criteria
- Pregnant or within 2 weeks post-partum at screening
- Immunocompromised (including HHC receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus [HIV] infection)
- <2 years old
- HHC who have received an investigational therapy within the 30 days or 5 drug-elimination half-lives, whichever is longer, prior to screening
- Diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional in the past 4 weeks.
- HHC previously included in the study
- HHC who plans to arrive home after 24 hours post IP randomization to Day 9 and is not willing to be consented as soon as possible upon arrival
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of HHC who become PCR+ for influenza by Day 5 post IP randomization, with virus subtype consistent with IP in their household. HHCs may be symptomatic or asymptomatic. The primary efficacy analysis population will consist of all enrolled unvaccinated HHCs of the randomized IPs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Day 5 (5 days) |
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E.5.2 | Secondary end point(s) |
1. Proportion of HHCs who become PCR+ for influenza by Day 5 post IP randomization, with virus subtype consistent with IP, AND meet symptomatic definition based on age group (≥2 to <12 years or ≥12 years) and baseline symptom status (“Symptomatic transmission by Day 5”).
2. Proportion of households with at least one HHC who meets the Primary Endpoint
3. Proportion of households with at least one HHC who meets the “Symptomatic transmission by Day 5” endpoint
4. Proportion of HHCs who become PCR+ for influenza by Day 9 post IP randomization, with virus subtype consistent with IP (“Virological transmission by Day 9”).
5. Proportion of HHCs who meet the “Virological transmission by Day 9” endpoint AND are symptomatic per the definition for symptoms in the “Symptomatic transmission by Day 5” endpoint.
6. Proportion of HHCs who become PCR+ for influenza by Day 9 (“Any virological infection by Day 9”)
7. Proportion of households with at least one HHC who meets the “Any virological infection by Day 9” endpoint
8. Proportion of HHCs who meet the “Any virological infection by Day 9” endpoint AND are symptomatic per the definition for symptoms in the “Symptomatic transmission by Day 5” endpoint
9. Proportion of households with at least one HHC who meets the “Any symptomatic infection by Day 9” endpoint
10. Percentage of IP with Adverse Events (AEs)
11. IP only: Change from baseline in health-related quality of life according to EuroQol 5 dimensions 5 (EQ-5D-5L; Appendix 3) questionnaire at Day 3 and Day 9 Visits
12. IP only: Change from Baseline in work productivity according to Work Productivity and Activity Impairment (WPAI) plus Classroom Impairment Questions Score at Day 9
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline to Day 5 (5 days)
2. Baseline up to Day 9 (9 days)
3. Baseline to Day 5 (5 days)
4. Baseline to Day 9 (9 days)
5. Baseline to Day 5 (5 days)
6-8. Baseline to Day 5 (5 days)
9-10. Baseline to Day 9 (9 days)
11. Day 3 and Day 9 (versus baseline)
12. Day 9 (versus baseline)
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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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |
Argentina |
Chile |
China |
Costa Rica |
Egypt |
France |
Greece |
Hong Kong |
Hungary |
India |
Israel |
Japan |
Mexico |
New Zealand |
Poland |
Singapore |
South Africa |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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. |
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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 |