A Surveillance Study of Susceptibility to Baloxavir Marboxil in Pediatric Participants With Influenza and Transmission of Influenza to Household Contacts

Official title

A Phase IIIb Multicenter, Single-arm, Open-label Surveillance Study of Susceptibility to Baloxavir Marboxil in Pediatric Patients With Influenza and Transmission of Influenza to Household Contacts

Overview

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' \<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. Participants will no longer be enrolled to Part B Transmission as per protocol version 3.

Interventions

• Drug Baloxavir Marboxil
  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 milligrams per kilogram \[mg/kg\]).

Primary outcome measures

• Part A: Percentage of Participants With Resistance-associated Pre-treatment Substitutions [Time frame: Day 1 (At Baseline)]
• Part A: Percentage of Participants With Resistance-associated Treatment-emergent Substitutions [Time frame: Days 4, 6 and 10]

Secondary outcome measures (9)

• 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) [Time frame: Days 4, 6 and 10]
• Part A: Percentage of IPs With Novel Treatment-emergent Mutations in Polymerase Acidic Protein (PA) [Time frame: Days 4, 6 and 10]
• Part A: Percentage of IPs With Resistance-associated Treatment-emergent Substitutions by Baseline Vaccination Status [Time frame: Days 4, 6 and 10]
• Part A: Percentage of IPs With Influenza Virus Type (A or B) and Subtype (A/H1 or A/H3) [Time frame: Day 1 (At Baseline)]
• Part A: Change From Baseline in Viral Titers by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) [Time frame: At Baseline (Day 1); Days 4, 6 and 10]
• Part A: Susceptibility to Baloxavir Marboxil by Phenotyping of Virus With Novel Genotypic PA Substitutions [Time frame: Days 4, 6 and 10]
• Part A: Number of IPs with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to Day 29]
• Part B: Percentage of HHCs With Transmission of Influenza Virus by Confirmed by Central RT-PCR, With Virus Subtype Consistent With the IP [Time frame: 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 [Time frame: Day 6, Day 10]

Eligibility criteria

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 start of 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 HHC

\[B\] 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 HHC" criteria

\[D\] Full-study HHC:

• Fulfills the "partial HHC" 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)

Exclusion Criteria (Part B):

• IPs who fulfil an exclusion criterion for Part A
• HHCs deemed to require influenza post-exposure prophylaxis with influenza antiviral treatment due to their risk of developing influenza-related complications in accordance with local guidelines or clinical practice
• HHCs diagnosed with influenza by health care professional in the past 4 weeks

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 28 centers

• Central Alabama Research — Birmingham
• Harrisburg Family Medical Center — Harrisburg
• Kendall South Medical Center Inc. — Miami
• Avanza Medical Research Center — Pensacola
• Tekton Research - Chamblee Georgia — Chamblee
• Tekton Research Lawrenceville — Lawrenceville
• Velocity Clinical Research at Primary Pediatrics Macon — Macon
• Clinical Research Prime — Idaho Falls
• … and 20 more centers

Poland · 11 centers

• IN VIVO Sp. z o.o. — Bydgoszcz
• NZOZ Vitamed — Bydgoszcz
• Centrum Medyczne Pratia Częstochowa — Częstochowa
• Niepubliczny Zaklad Opieki Zdrowotnej "Amed" — Grójec
• Vita Longa Sp. z o.o. — Katowice
• Centrum Medyczne K2J2 — Lodz
• NZLA Michalkowice Rybarczyk i partnerzy, Spolka Lekarska — Siemianowice Śląskie
• Jaroslaw Kierkus Prywatna Prakyka Lekarska — Warsaw
• … and 3 more centers

Bulgaria · 8 centers

• Medical Centre "Asklepii", OOD — Dupnitsa
• MHAT " St. Ivan Rilski " Kozloduy — Kozloduy
• MHAT Stamen Iliev AD — Montana
• MHAT City Clinic - Saint George — Montana
• SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd. — Rousse
• MHAT Sliven - Military Medial Academy — Sliven
• AGPSMP Pediatric diseases South park OOD — Sofia
• Medical Center Hera Sofia — Sofia

Spain · 4 centers

• Complejo Hospitalario Universitario de Santiago (CHUS) — Santiago de Compostela
• Hospital Infantil Universitario Nino Jesus — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitari i Politècnic La Fe — Valencia

Identifiers

NCT: NCT06094010 · CV44536 · 2023-504672-22-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗