Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households

NCT ID: NCT03969212

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-10
• Study Completion Date: 2024-05-10

Brief Summary

Otherwise healthy index patients (IP) are randomized to either baloxavir marboxil or placebo if their influenza symptoms onset was within 48 hours of screening. Their households are enrolled within 24 hours of randomization if at least 1 household contacts (HHC) have not received influenza vaccine within 6 months of screening and if all HHC screen negative for influenza infection. The main endpoints are assessed based on multiple respiratory swabs, obtained from both IP and HHC up to 9 (+/-1) days post IP randomization, and through the assessment of symptoms.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Baloxavir Marboxil

Participants who are IPs will receive a single oral dose of baloxavir marboxil. HHCs of the IPs will not receive study medication.

Group Type: EXPERIMENTAL

Baloxavir Marboxil

Intervention Type: DRUG

IPs less than 12 years old will receive either 2 mg/kg (if weight less than 20 kg) or 40 mg (if weight more than or equal to 20 kg) of Baloxavir Marboxil as oral suspension. IPs more than or equal to 12 years old will receive either 40 mg (if weight less than 80 kg) or 80 mg (if weight more than or equal to 80 kg) of Baloxavir Marboxil as tablets. HHCs of IPs will not receive study medication.

Placebo

Participants who are IPs will receive a single oral dose of placebo. HHCs of the IPs will not receive study medication.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

IPs less than 12 years old will receive placebo oral suspension and those above 12 years will receive placebo tablets. HHCs of IPs will not receive study medication.

Interventions

Baloxavir Marboxil

IPs less than 12 years old will receive either 2 mg/kg (if weight less than 20 kg) or 40 mg (if weight more than or equal to 20 kg) of Baloxavir Marboxil as oral suspension. IPs more than or equal to 12 years old will receive either 40 mg (if weight less than 80 kg) or 80 mg (if weight more than or equal to 80 kg) of Baloxavir Marboxil as tablets. HHCs of IPs will not receive study medication.

Intervention Type: DRUG

Placebo

IPs less than 12 years old will receive placebo oral suspension and those above 12 years will receive placebo tablets. HHCs of IPs will not receive study medication.

Intervention Type: DRUG

Other Intervention Names

Xofluza

Eligibility Criteria

Inclusion Criteria

Index Patients (IPs):

• 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 on cobas® SARS-CoV-2 and influenza A/B or other point-of-care / local laboratory results.
• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and Influenza A/B test or other point-of-care / local laboratory result
• Presence of (a) fever (>=38.0 °C per tympanic or rectal thermometer; >=37.5 °C per axillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle or joint pain, fatigue).
• The time interval between the onset of fever or influenza symptoms and the pre-dose examinations is 48 hours or less.
• Women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures specified in the protocol

All HHCs (Part 1):

• PCR (-) or RIDT (-) based on cobas® SARS-CoV-2 and influenza A/B or other local point-of-care / local laboratory result.
• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and Influenza A/B or other POC / local laboratory result.

Full study HHCs (part 2) 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. Alternatively, mild symptoms are permissible if determined by the investigator to be due to a preexisting condition.
• Temperature <38.0 °C (tympanic).
• Will reside in the index patient's house for at least 7 of the next 9 days and will be present for scheduled study visits.
• Willing and able to measure and record temperature, or have another household member perform the task on his or her behalf. Furthermore, a responsible adult will assume responsibility to oversee or perform this task on behalf of minors.
• In the 6 months prior to screening: a) Has not been diagnosed with influenza by a healthcare professional b) Has not received BXM, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, favipiravir or amantadine.
• Does not have a moderate or worse active infections OR infections requiring systemic (e.g., oral or intravenous) or otherwise internally administered (e.g., inhaled, intrathecal) antibiotic/antiviral/antifungal therapy, (topical therapies for mild external infections allowed).

Exclusion Criteria

IPs:

• IPs with severe influenza virus infection requiring inpatient treatment.
• IPs judged by the investigator to be at high risk for complications of influenza.
• IP is ≥12 years old and unable to swallow tablets (not applicable to IPs 5 to 11 year olds who will receive oral suspension).
• Women who are breastfeeding or have a positive pregnancy test in the pre-dose examinations.
• IPs with concurrent (non-influenza) infections requiring systemic antimicrobial and/or antiviral therapy at the pre-dose examinations.
• IPs who have received baloxavir marboxil, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, favipiravir or amantadine, or an investigational drug, within 30 days or 5 drug-elimination half-lives, whichever is longer, prior to screening.
• IPs who have received an investigational monoclonal antibody for a viral disease in the last year.
• Known hypersensitivity to baloxavir marboxil or the drug product excipients.
• IP previously included in the study

HHC:

• Pregnant or within 2 weeks post-partum at screening.
• Immunocompromised.
• Less than 2 years old.
• 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 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.
• HHC previously included in the study.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Cahaba Research, Inc.

Birmingham, Alabama, United States

Cahaba Research, Inc

Pelham, Alabama, United States

Precision Trials

Phoenix, Arizona, United States

Hope Clinical Research

Canoga Park, California, United States

Long Beach Clinical Trials

Long Beach, California, United States

Downtown LA Research Center

Los Angeles, California, United States

Probe Clinical Research

Riverside, California, United States

MD Strategies Research Centers

San Diego, California, United States

Cherry Creek Family Practice

Denver, Colorado, United States

Proactive Clinical Research, LLC

Fort Lauderdale, Florida, United States

Helios Clinical Research, Inc (former Ventavia Research Group)

Kissimmee, Florida, United States

South Florida Research Center, Inc.

Miami, Florida, United States

Cordova Research Institute, LLC

Miami, Florida, United States

Research Institute of South Florida Inc

Miami, Florida, United States

Kendall South Medical Center Inc.

South Miami, Florida, United States

Agile Clinical Research Trials

Atlanta, Georgia, United States

Clinical Research Prime

Idaho Falls, Idaho, United States

Mishawaka Osteopathic Clinic

Mishawaka, Indiana, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercury Street Medical Group

Butte, Montana, United States

Montana Medical Research LLC

Missoula, Montana, United States

Accent Clinical Trials

Las Vegas, Nevada, United States

Excel Clinical Research

Las Vegas, Nevada, United States

OnSite Clinical Solutions LLC

Charlotte, North Carolina, United States

Burke Primary Care

Morganton, North Carolina, United States

Hometown Urgent Care and Occupational Health - Springdale

Cincinnati, Ohio, United States

Tristar Clinical Investigations

Philadelphia, Pennsylvania, United States

Frontier Clinical Research

Scottdale, Pennsylvania, United States

Frontier Clinical Research

Smithfield, Pennsylvania, United States

Frontier Clinical Research

Smithfield, Pennsylvania, United States

Jedda Enterprises dba Galen Clinical Research

Greer, South Carolina, United States

AFC Urgent Care-Gunbarrell

Chattanooga, Tennessee, United States

Helios Clinical Research, Inc (former Ventavia Research Group)

Jackson, Tennessee, United States

City Doc Urgent Care-Dallas/Ft. Worth

Dallas, Texas, United States

Southwest Family Medicine Associates

Dallas, Texas, United States

Premier Pulmonary Critical Care and Sleep Medicine

Denison, Texas, United States

Pioneer Research Solutions

Houston, Texas, United States

Vilo Research Group

Houston, Texas, United States

Fairway Medical Clinic

Houston, Texas, United States

Mercury Clinical Research

Houston, Texas, United States

Family Practice Center

McAllen, Texas, United States

Sun Research Institute

San Antonio, Texas, United States

Frontier Clinical Research

Kingwood, West Virginia, United States

Medical Centre "Asklepii", OOD

Dupnitsa, , Bulgaria

Medical Center Hera Eood

Montana, , Bulgaria

MHAT Sveta Paraskeva

Pleven, , Bulgaria

Medizinski Zentrar-1-Sevlievo EOOD

Sevlievo, , Bulgaria

MHAT Sliven - Military Medial Academy

Sliven, , Bulgaria

Medical Center Hera Sofia

Sofia, , Bulgaria

MHAT Sveta Sofia

Sofia, , Bulgaria

Capital Medical University Beijing Hospital of Traditional Chinese Medicine

Beijing, , China

Beijing You An Hospital

Beijing, , China

China-Japan Friendship Hospital

Beijing, , China

Beijing Tsinghua Changgung Hospital

Beijing, , China

West China Hospital, Sichuan University

Chengdu, , China

The Third People's Hospital of Hainan Province

Sansha, , China

Shenzhen People's Hospital

Shenzhen, , China

Shenzhen children's hospital

Shenzhen, , China

Taizhou People's Hospital

Taizhou, , China

The First Affiliated Hospital of Wenzhou Medical College

Wenzhou, , China

General Hospital of Ningxia Medical University

Yinchuan, , China

Henan Provincial People's Hospital

Zhengzhou, , China

ICIMED Instituto de Investigación en Ciencias Médicas

San José, , Costa Rica

Laiko General Hospital - Uni of Athens

Athens, , Greece

Sotiria General Hospital of Athens

Athens, , Greece

Attikon University General Hospital

Chaïdári, , Greece

Obudai Egeszsegugyi Centrum Kft.

Budapest, , Hungary

II. Háziorvosi Körzet

Hosszúhetény, , Hungary

Gyermekháziorvosi rendel?- Dr. Újhelyi János

Nyíregyháza, , Hungary

OEC Clinical Research

Zalaegerszeg, , Hungary

JSS Hospital

Mysuru, Karnataka, India

Kiryat Motzkin Maccabi Medical Center

Kiryat Motzkin, , Israel

Maccabi health services - Moked Hashalom

Tel Aviv, , Israel

Toda Internal Medicine & Neurology Clinic

Akashi, , Japan

Medical Corporation Houmankai?Umezu?Clinic

Chikushino-shi, , Japan

Shin Komonji Hospital

Fukuoka, , Japan

Irie Naika Syounika Iin

Fukuoka, , Japan

Kimura Siro Clinic

Fukuoka, , Japan

Iguchi Clinic

Fukuyama, , Japan

Mashiba Clinic

Hannō, , Japan

Fujimaki Ent Clinic

Ichikawa, , Japan

Hisaki Family Clinic

Ichikawa, , Japan

Moriyama Otolaryngology

Kagoshima, , Japan

Kamoike ENT Allergy Clinic

Kagoshima, , Japan

Clinic Kashiwanoha

Kashiwa, , Japan

Kamezawa Clinic

Kasugai, , Japan

Oishi Clinic

Kasuyagun, , Japan

Takahashi naika

Kawasaki, , Japan

Kanagawa Himawari Clinic

Kawasaki, , Japan

Osaki Internal and Respiratory Clinic,

Kitakyushu, , Japan

Morizono medical clinic

Kitakyushu, , Japan

Sato ENT Clinic

Kitakyushu, , Japan

Kiheibashi Otolaryngology

Kodaira, , Japan

Medical corporation Shirayurikai Swing Nozaki Clinic

Musashino, , Japan

Yaesu Clinic

Naha, , Japan

Horikawa Clinic

Nonoichi, , Japan

Lee's Clinic

Osaka, , Japan

Kitada Clinic

Osaka, , Japan

Sunami Internal medicine Clinic

Osaka, , Japan

Funai Ear Nose Throat Clinic

Ōita, , Japan

Saga Memorial Hospital

Saga, , Japan

Segawa Hospital

Saitama, , Japan

Uehara Clinic

Sapporo, , Japan

Aiiku Hospital

Sapporo, , Japan

Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai

Shinagawa City, , Japan

Wakasa Clinic

Tokorozawa, , Japan

Seiwa Clinic

Tokyo, , Japan

Denenchofu Family Clinic

Tokyo, , Japan

Sato Clinic

Tokyo, , Japan

Sekino Hospital

Toshima City, , Japan

Takeru CLINIC

Toyohashi, , Japan

Tsuchiura Beryl Clinic

Tsuchiura, , Japan

Medical corporation Seijinkai Takei Clinic

Tsuru, , Japan

Gushiken-Cardiology and Internal medicine

Urasoe, , Japan

Uranishi Clinic

Urasoe, , Japan

Yotsukaido Tokushukai Medical Center

Yotsukaidō, , Japan

Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.

Guadalajara, Jalisco, Mexico

Centro Respiratorio de México

México, Mexico CITY (federal District), Mexico

Centro de Estudios Clinicos de Queretaro (CECLIQ)

Querétaro City, Querétaro, Mexico

EME RED

Mérida, Yucatán, Mexico

Merida | Investigacion Clinica

Mérida, Yucatán, Mexico

KLIMED

Bialystok, , Poland

Centrum Medyczne Lukamed Joanna Luka

Chojnice, , Poland

KO-MED Centra Kliniczne Sp. z o.o.

Puławy, , Poland

CLINHOUSE Sp z o.o.

Zabrze, , Poland

Fundacion de Investigacion de Diego

San Juan, , Puerto Rico

Into Research

Groenkloof, , South Africa

Newtown Clinical Research

Johannesburg, , South Africa

Langeberg Clinical Trials

Kraaifontein, , South Africa

Midrand Medical Centre

Midrand, , South Africa

Centro de Salud Las Aguilas

Madrid, , Spain

Ankara Bilkent City Hospital

Ankara, , Turkey (Türkiye)

Ankara University Faculty of Medicine Cebeci Hospital

Ankara, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

Akdeniz University Medical Faculty

Antalya, , Turkey (Türkiye)

Atakent Acibadem Private Hosptial Halkali Merkez Mh.,

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Dokuz Eylul University Medical Faculty

Izmir, , Turkey (Türkiye)

Kocaeli University Medical Faculty

Kocaeli, , Turkey (Türkiye)

Karadeniz Technical Uni School of Medicine

Trabzon, , Turkey (Türkiye)

Preston Hill Surgery

Harrow, , United Kingdom

Countries

United States; Bulgaria; China; Costa Rica; Greece; Hungary; India; Israel; Japan; Mexico; Poland; Puerto Rico; South Africa; Spain; Turkey (Türkiye); United Kingdom

References

Monto AS, Kuhlbusch K, Bernasconi C, Cao B, Cohen HA, Graham E, Hurt AC, Katugampola L, Kamezawa T, Lauring AS, McLean B, Takazono T, Widmer A, Wildum S, Cowling BJ. Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza. N Engl J Med. 2025 Apr 24;392(16):1582-1593. doi: 10.1056/NEJMoa2413156.

Reference Type: DERIVED

PMID: 40267424 (View on PubMed)

Komeda T, Takazono T, Hosogaya N, Ogura E, Fujiwara M, Miyauchi H, Ajisawa Y, Iwata S, Watanabe H, Honda K, Kitanishi Y, Hara K, Mukae H. Comparison of Household Transmission of Influenza Virus From Index Patients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study. Clin Infect Dis. 2021 Jun 1;72(11):e859-e867. doi: 10.1093/cid/ciaa1622.

Reference Type: DERIVED

PMID: 33103200 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-004056-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MV40618

Identifier Type: -

Identifier Source: org_study_id