Influenza
Conditions
Brief summary
This study consists of two parts: Part A Surveillance and Part B Transmission. The main purpose of Part A is to evaluate the prevalence of pre-dose and treatment-emergent amino acid substitutions in pediatric participants' susceptibility \<12 years with influenza treated with baloxavir marboxil. Part B will include a subset of Part A participants who have household contacts (HHCs) recruited to the study. Part B will evaluate the incidence of onward influenza transmission from pediatric index participants (IPs) under 5 years of age and those aged 5 to under 12 years, treated with baloxavir marboxil, to their HHCs.
Interventions
Baloxavir marboxil will be administered as an oral suspension per body weight (≥80 kilograms (kg): 80 milligrams (mg); ≥20 kg to \< 80 kg: 40 mg; \<20 kg: 2 mg/kg).
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Weeks to 11 Years
Healthy volunteers
No
Inclusion criteria
(Part A): * Participants with symptoms suggestive of influenza based on investigator's judgement with diagnosis confirmed by a positive local influenza test within 24 hours before full study screening * Participants with a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test within 48 hours before full study screening * Time interval between onset of influenza symptoms and the pre-dose examinations at screening is 48 hours or less Inclusion Criteria (Part B): \[A\] IP: * Eligible to take part in Part A * Lives in a household with a HHC willing to be recruited as full household contact \[B\] HHCs: \- Each HHC living in the home of an IP at the time of IP treatment must be screened for partial or full-study HHC eligibility \[C\] Partial HHC: * Starts screening within 1 calendar day after IP treatment * Negative influenza and SARS-CoV-2 test at screening after IP's treatment with baloxavir marboxil * HHC lives in a household where 1 or more HHCs meet the full-study HHC requirements AND at least 1 full-study HHC has not received the influenza vaccine within 6 months prior to screening * HHC lives in a household where 1 or more HHCs meet the full-study HHC requirements AND at least 1 full-study HHC has not received the influenza vaccine within 6 months prior to screening. * HHC lives with other HHCs (if applicable) who fulfill all the "Partial household contact" criteria \[D\] Full-study HHC: * Fulfills the "Partial household contact" criteria * Agrees to participate in the full study * Will reside in the IP's house for at least 12 of the next 15 days and will be present for scheduled study visits * No influenza symptoms within 7 days prior to screening * Does not have a moderate or worse active infections OR infections requiring systemic or otherwise internally administered or otherwise internally administered antibiotic/antiviral/antifungal therapy
Exclusion criteria
(Part A): * Participants with severe influenza virus infection requiring inpatient treatment * Severely immunocompromised participants \[including participants receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus (HIV) infection\] as defined by the investigator * Participants with concurrent (non-influenza) infections requiring systemic anti-microbial and/or anti-viral therapy at the pre-dose examinations * Treatment with baloxavir marboxil, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir or amantadine within 30 days prior to screening * Treatment with an investigational influenza-specific monoclonal antibody within 6 months or 5 half-lives, whichever is longer, prior to screening * Treatment with an investigational therapy within 30 days or 5 half-lives, whichever is longer, prior to screening * Known hypersensitivity to baloxavir marboxil or the drug product excipients * Females who have commenced menarche (i.e., child-bearing potential)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Percentage of Participants With Resistance-associated Pre-treatment Substitutions | Day 1 (Baseline) |
| Part A: Percentage of Participants With Resistance-associated Treatment-emergent Substitutions | Days 4, 6 and 10 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of IPs With Resistance-associated Treatment-emergent Substitutions by Age Groups (<5 Years [< 1 Year, ≥ 1 Year to < 5 Years], and 5 to < 12 Years) | Days 4, 6 and 10 | — |
| Part A: Percentage of IPs With Novel Treatment-emergent Mutations in Polymerase Acidic Protein (PA) | Days 4, 6 and 10 | — |
| Part A: Percentage of IPs With Resistance-associated Treatment-emergent Substitutions by Baseline Vaccination Status | Days 4, 6 and 10 | — |
| Part A: Percentage of IPs With Influenza Virus Type (A or B) and Subtype (A/H1 or A/H3) | Day 1 (Baseline) | — |
| Part A: Change From Baseline in Viral Titers by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) | Baseline (Day 1); Days 4, 6 and 10 | — |
| Part A: Susceptibility to Baloxavir Marboxil by Phenotyping of Virus With Novel Genotypic PA Substitutions | Days 4, 6 and 10 | — |
| Part A: Number of IPs with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 29 | AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). |
| Part B: Percentage of HHCs With Transmission of Influenza Virus by Confirmed by Central RT-PCR, With Virus Subtype Consistent With the IP | Day 6, Day 10 | — |
| Part B: Percentage of HHCs Who Develops Influenza Symptoms With Transmission of Influenza Virus Confirmed by Central RT-PCR, With Virus Subtype Consistent With the IP | Day 6, Day 10 | — |
Countries
Bulgaria, Poland, Spain, United States
Contacts
CONTACTReference Study ID Number: CV44536 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed