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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Influenza
• Intervention / Treatment: Drug: Baloxavir Marboxil

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: CV44536 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Bulgaria
  • Dupnitsa, Bulgaria, 2600
    • Completed
    • Medical Centre "Asklepii", OOD
  • Kozloduy, Bulgaria, 3320
    • Recruiting
    • MHAT " St. Ivan Rilski " Kozloduy
  • Montana, Bulgaria, 3403
    • Recruiting
    • MHAT City Clinic - Saint George
  • Montana, Bulgaria, 3400
    • Completed
    • MHAT Stamen Iliev AD
  • Rousse, Bulgaria, 7002
    • Completed
    • SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
  • Sliven, Bulgaria, 8800
    • Recruiting
    • MHAT Sliven - Military Medial Academy
  • Sofia, Bulgaria, 1421
    • Recruiting
    • AGPSMP Pediatric diseases South park OOD
  • Sofia, Bulgaria, 1510
    • Completed
    • Medical Center Hera Sofia
• Poland
  • Bydgoszcz, Poland, 85-079
    • Recruiting
    • NZOZ Vitamed
  • Bydgoszcz, Poland, 85-048
    • Recruiting
    • In Vivo Sp. z o.o.
  • Częstochowa, Poland, 42-200
    • Recruiting
    • Centrum Medyczne Pratia Czestochowa
  • Grójec, Poland, 05-600
    • Recruiting
    • Niepubliczny Zaklad Opieki Zdrowotnej "Amed"
  • Katowice, Poland, 40-748
    • Recruiting
    • Vita Longa Sp. z o.o.
  • Lodz, Poland, 92-108
    • Completed
    • Centrum Medyczne K2J2
  • Siemianowice Śląskie, Poland, 41-103
    • Recruiting
    • NZLA Michalkowice Rybarczyk i partnerzy, Spolka Lekarska
  • Warsaw, Poland, 04-501
    • Recruiting
    • Jaroslaw Kierkus Prywatna Prakyka Lekarska
  • Wo?omin, Poland, 05-200
    • Withdrawn
    • Centrum Medyczne K2J2
  • Wroclaw, Poland, 53-149
    • Recruiting
    • Vistamed & Vertigo Spó?Ka Z Ograniczon? Odpowiedzialno?Ci?
  • Łęczna, Poland, 21-010
    • Recruiting
    • NZOZ Salmed
• Spain
  • Madrid, Spain, 28041
    • Withdrawn
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28009
    • Withdrawn
    • Hospital Infantil Universitario Niño Jesús
  • Valencia, Spain, 46026
    • Completed
    • Hospital Universitari i Politècnic La Fe
  • LA Coruna
    • Santiago de Compostela, LA Coruna, Spain, 15706
      • Withdrawn
      • Complejo Hospitalario Universitario de Santiago (CHUS)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Recruiting
      • Central Alabama Research
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
      • Recruiting
      • Harrisburg Family Medical Center
  • Florida
    • Miami, Florida, United States, 33185
      • Recruiting
      • Kendall South Medical Center Inc.
    • Pensacola, Florida, United States, 32503
      • Recruiting
      • Avanza Medical Research Center
  • Georgia
    • Chamblee, Georgia, United States, 30341
      • Withdrawn
      • Tekton Research - Chamblee Georgia
    • Lawrenceville, Georgia, United States, 30043
      • Withdrawn
      • Tekton Research Lawrenceville
    • Macon, Georgia, United States, 31210
      • Completed
      • Velocity Clinical Research at Primary Pediatrics Macon
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Recruiting
      • Clinical Research Prime
  • Indiana
    • Mishawaka, Indiana, United States, 46544
      • Recruiting
      • Mishawaka Osteopathic Clinic
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Recruiting
      • Kentucky Pediatric Research Center
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Recruiting
      • Velocity Clinical Research Lafayette
    • Slidell, Louisiana, United States, 31210
      • Completed
      • Velocity Clinical Research, Slidell
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Recruiting
      • Velocity Clinical Research, Grand Island
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Recruiting
      • Machuca Family Medicine
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Recruiting
      • Ohio Pediatric Research Association
    • Middleburg Heights, Ohio, United States, 44130-3643
      • Recruiting
      • Helios Clinical Research, Inc (former Ventavia Research Group)
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Recruiting
      • Frontier Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Recruiting
      • Coastal Pediatric Research
  • Texas
    • Beaumont, Texas, United States, 77706
      • Recruiting
      • Tekton Research - Beaumont
    • Dallas, Texas, United States, 75287
      • Completed
      • Oak Cliff Research Company, LLC
    • Houston, Texas, United States, 77099
      • Recruiting
      • Pioneer Research Solutions
    • Houston, Texas, United States, 77087
      • Completed
      • Mercury Clinical Research
    • Richardson, Texas, United States, 75287
      • Recruiting
      • Oak Cliff Research Company, LLC
    • San Antonio, Texas, United States, 78215
      • Withdrawn
      • Sun Research Institute
    • San Antonio, Texas, United States, 78229
      • Completed
      • Tekton Research
    • Sugar Land, Texas, United States, 77479
      • Recruiting
      • Siena Research Network
  • Utah
    • West Jordan, Utah, United States, 84088
      • Recruiting
      • Velocity Clinical Research, Salt Lake City
  • West Virginia
    • Kingwood, West Virginia, United States, 26537
      • Active, not recruiting
      • Frontier Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baloxavir Marboxil; Participants will receive a single oral dose of baloxavir marboxil on Day 1 (based on body weight and age). HHCs related to IPs will be enrolled but will not receive treatment.	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]).; Other Names: XOFLUZA®; RO7191686

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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)	AEs were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).	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		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
Part A: Percentage of IPs With Influenza Virus Type (A or B) and Subtype (A/H1 or A/H3)		Day 1 (At Baseline)
Part A: Change From Baseline in Viral Titers by Quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)		At Baseline (Day 1); Days 4, 6 and 10

Other Outcome Measures

Outcome Measure	Time Frame
Percentage of HHCs Who Become PCR (+) for Influenza Bearing a PA/I38X Substitution (or Other Identified Substitution) Including All Data up to Day 15	Up to Day 15

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): May 11, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiviral Agents; baloxavir
• Other Study ID Numbers: CV44536; 2023-504672-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No