Clinical trial NCT03969212: Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households
Official title: A Phase IIIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza From Otherwise Healthy Patients to Household Contacts
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-05-31
Enrollment: 4138
Sex: ALL
Minimum age (years): 5
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.
* IP lives in a household where: (1) 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; (2) All HHCs are expected to meet the key HHC inclusion criteria; (3) \>=1 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: 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.
* 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 criteria (part 1).
* HHC lives in a household where ≥1 HHCs meet all of the following: Start screening within 24 hours after IP randomization; Have NOT received the influenza vaccine within 6 months prior to screening; and Fulfill full study HHC inclusion criteria part 2.

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
* IP lives with an HHC who, based on available information, meets the HHC exclusion criteria

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.

Primary outcomes:
measure: Percentage of HHCs With Virological Influenza Transmission by Day 5
timeFrame: Baseline (Day 1) to Day 5
Secondary outcomes:
measure: Percentage of HHCs With Symptomatic Influenza Transmission by Day 5
timeFrame: Baseline (Day 1) to Day 5
measure: Percentage of Households (HHs) With Virological Influenza Transmission at Household Level by Day 5
timeFrame: Baseline (Day 1) to Day 5
measure: Percentage of HHs With Symptomatic Influenza Transmission at Household Level by Day 5
timeFrame: Baseline (Day 1) to Day 5
measure: Percentage of HHCs With Virological Influenza Transmission by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Percentage of HHCs With Symptomatic Influenza Transmission by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Percentage of HHCs With Any Virological Infection by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Percentage of HHs With Any Virological Infection at HH Level by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Percentage of HHCs With Any Symptomatic Infection by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Percentage of HHs With Any Symptomatic Infection at HH Level by Day 9
timeFrame: Baseline (Day 1) to Day 9
measure: Number of IPs With Adverse Events (AEs)
timeFrame: Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)
measure: Number of IPs With Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cahaba Research, Inc.
state: Alabama
city: Pelham
country: United States
facility: Cahaba Research, Inc
state: Alabama
city: Phoenix
country: United States
facility: Precision Trials
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Downtown LA Research Center
state: California
city: Riverside
country: United States
facility: Probe Clinical Research
state: California
city: San Diego
country: United States
facility: MD Strategies Research Centers
state: California
city: Denver
country: United States
facility: Cherry Creek Family Practice
state: Colorado
city: Fort Lauderdale
country: United States
facility: Proactive Clinical Research, LLC
state: Florida
city: Kissimmee
country: United States
facility: Helios Clinical Research, Inc (former Ventavia Research Group)
state: Florida
city: Miami
country: United States
facility: South Florida Research Center, Inc.
state: Florida
city: Miami
country: United States
facility: Cordova Research Institute, LLC
state: Florida
city: Miami
country: United States
facility: Research Institute of South Florida Inc
state: Florida
city: South Miami
country: United States
facility: Kendall South Medical Center Inc.
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Mishawaka
country: United States
facility: Mishawaka Osteopathic Clinic
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group
state: Montana
city: Missoula
country: United States
facility: Montana Medical Research LLC
state: Montana
city: Las Vegas
country: United States
facility: Accent Clinical Trials
state: Nevada
city: Las Vegas
country: United States
facility: Excel Clinical Research
state: Nevada
city: Charlotte
country: United States
facility: OnSite Clinical Solutions LLC
state: North Carolina
city: Morganton
country: United States
facility: Burke Primary Care
state: North Carolina
city: Cincinnati
country: United States
facility: Hometown Urgent Care and Occupational Health - Springdale
state: Ohio
city: Middleburg Heights
country: United States
facility: Helios Clinical Research, Inc (former Ventavia Research Group)
state: Ohio
city: Philadelphia
country: United States
facility: Tristar Clinical Investigations
state: Pennsylvania
city: Scottdale
country: United States
facility: Frontier Clinical Research
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research
state: Pennsylvania
city: Greer
country: United States
facility: Jedda Enterprises dba Galen Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: AFC Urgent Care-Gunbarrell
state: Tennessee
city: Jackson
country: United States
facility: Helios Clinical Research, Inc (former Ventavia Research Group)
state: Tennessee
city: Dallas
country: United States
facility: City Doc Urgent Care-Dallas/Ft. Worth
state: Texas
city: Dallas
country: United States
facility: Southwest Family Medicine Associates
state: Texas
city: Denison
country: United States
facility: Premier Pulmonary Critical Care and Sleep Medicine
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Houston
country: United States
facility: Vilo Research Group
state: Texas
city: Houston
country: United States
facility: Fairway Medical Clinic
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: McAllen
country: United States
facility: Family Practice Center
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Kingwood
country: United States
facility: Frontier Clinical Research
state: West Virginia
city: Morgantown
country: United States
facility: Frontier Clinical Research
state: West Virginia
city: Dupnitsa
country: Bulgaria
facility: Medical Centre "Asklepii", OOD
city: Montana
country: Bulgaria
facility: Medical Center Hera Eood
city: Pleven
country: Bulgaria
facility: MHAT Sveta Paraskeva
city: Sevlievo
country: Bulgaria
facility: Medizinski Zentrar-1-Sevlievo EOOD
city: Sliven
country: Bulgaria
facility: MHAT Sliven - Military Medial Academy
city: Sofia
country: Bulgaria
facility: Medical Center Hera Sofia
city: Sofia
country: Bulgaria
facility: MHAT Sveta Sofia
city: Beijing City
country: China
facility: Capital Medical University Beijing Hospital of Traditional Chinese Medicine
city: Beijing City
country: China
facility: Beijing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: Beijing Ditan Hospital
city: Beijing
country: China
facility: Beijing You An Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Sansha City
country: China
facility: The Third People's Hospital of Hainan Province
city: Sanya
country: China
facility: The Third People's Hospital of Hainan Province
city: Shenzhen City
country: China
facility: Shenzhen children's hospital
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Taizhou City
country: China
facility: Taizhou People's Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical College
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: San José
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Athens
country: Greece
facility: Laiko General Hospital - Uni of Athens
city: Athens
country: Greece
facility: Sotiria General Hospital of Athens
city: Chaidari
country: Greece
facility: Attikon University General Hospital
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Hosszúhetény
country: Hungary
facility: II. Háziorvosi Körzet
city: Nyíregyháza
country: Hungary
facility: Gyermekháziorvosi rendel?- Dr. Újhelyi János
city: Zalaegerszeg
country: Hungary
facility: OEC Clinical Research
city: Mysuru
country: India
facility: JSS Hospital
state: Karnataka
city: Kiryat Motzkin
country: Israel
facility: Kiryat Motzkin Maccabi Medical Center
city: Kiryat Motzkin
country: Israel
facility: Maccabi health services
city: Tel Aviv
country: Israel
facility: Maccabi health services - Moked Hashalom
city: Akashi
country: Japan
facility: Toda Internal Medicine & Neurology Clinic
city: Chikushino
country: Japan
facility: Medical Corporation Houmankai?Umezu?Clinic
city: Fukuoka
country: Japan
facility: Shin Komonji Hospital
city: Fukuoka
country: Japan
facility: Irie Naika Syounika Iin
city: Fukuoka
country: Japan
facility: Kimura Siro Clinic
city: Fukuyama
country: Japan
facility: Iguchi Clinic
city: Hanno
country: Japan
facility: Mashiba Clinic
city: Ichikawa
country: Japan
facility: Fujimaki Ent Clinic
city: Ichikawa
country: Japan
facility: Hisaki Family Clinic
city: Kagoshima
country: Japan
facility: Moriyama Otolaryngology
city: Kagoshima
country: Japan
facility: Kamoike ENT Allergy Clinic
city: Kashiwa
country: Japan
facility: Clinic Kashiwanoha
city: Kasugai
country: Japan
facility: Kamezawa Clinic
city: Kasuyagun
country: Japan
facility: Oishi Clinic
city: Kawasaki
country: Japan
facility: Takahashi naika
city: Kawasaki
country: Japan
facility: Kanagawa Himawari Clinic
city: Kitakyushu
country: Japan
facility: Osaki Internal and Respiratory Clinic,
city: Kitakyushu
country: Japan
facility: Morizono medical clinic
city: Kitakyushu
country: Japan
facility: Sato ENT Clinic
city: Kodaira
country: Japan
facility: Kiheibashi Otolaryngology
city: Musashino
country: Japan
facility: Medical corporation Shirayurikai Swing Nozaki Clinic
city: Naha
country: Japan
facility: Yaesu Clinic
city: Nonoichi
country: Japan
facility: Horikawa Clinic
city: Oita
country: Japan
facility: Funai Ear Nose Throat Clinic
city: Osaka
country: Japan
facility: Lee's Clinic
city: Osaka
country: Japan
facility: Kitada Clinic
city: Osaka
country: Japan
facility: Sunami Internal medicine Clinic
city: Saga
country: Japan
facility: Saga Memorial Hospital
city: Saitama
country: Japan
facility: Segawa Hospital
city: Sapporo
country: Japan
facility: Uehara Clinic
city: Sapporo
country: Japan
facility: Aiiku Hospital
city: Shinagawa
country: Japan
facility: Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
city: Tokorozawa
country: Japan
facility: Wakasa Clinic
city: Tokyo
country: Japan
facility: Seiwa Clinic
city: Tokyo
country: Japan
facility: Denenchofu Family Clinic
city: Tokyo
country: Japan
facility: Sato Clinic
city: Toshima
country: Japan
facility: Sekino Hospital
city: Toyohashi
country: Japan
facility: Takeru CLINIC
city: Tsuchiura
country: Japan
facility: Tsuchiura Beryl Clinic
city: Tsuru
country: Japan
facility: Medical corporation Seijinkai Takei Clinic
city: Urasoe
country: Japan
facility: Gushiken-Cardiology and Internal medicine
city: Urasoe
country: Japan
facility: Uranishi Clinic
city: Yotsukaido
country: Japan
facility: Yotsukaido Tokushukai Medical Center
city: Guadalajara
country: Mexico
facility: Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
state: Jalisco
city: Mexico
country: Mexico
facility: Centro Respiratorio de México
state: Mexico CITY (federal District)
city: Querétaro
country: Mexico
facility: Centro de Estudios Clinicos de Queretaro (CECLIQ)
state: Queretaro
city: Mérida
country: Mexico
facility: EME RED
state: Yucatan
city: Mérida
country: Mexico
facility: Merida | Investigacion Clinica
state: Yucatan
city: Bia?ystok
country: Poland
facility: KLIMED
city: Chojnice
country: Poland
facility: Centrum Medyczne Lukamed Joanna Luka
city: Pu?awy
country: Poland
facility: KO-MED Centra Kliniczne Sp. z o.o.
city: Zabrze
country: Poland
facility: CLINHOUSE Sp z o.o.
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
city: Johannesburg
country: South Africa
facility: Newtown Clinical Research
city: Kraaifontein
country: South Africa
facility: Langeberg Clinical Trials
city: Midrand
country: South Africa
facility: Midrand Medical Centre
city: Pretoria
country: South Africa
facility: Into Research
city: Madrid
country: Spain
facility: Centro de Salud Las Aguilas
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine Cebeci Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Istanbul
country: Turkey
facility: Atakent Acibadem Private Hosptial Halkali Merkez Mh.,
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Technical Uni School of Medicine
city: Harrow
country: United Kingdom
facility: Preston Hill Surgery
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.