Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
Influenza
About this trial
This is an interventional treatment trial for Influenza
Eligibility Criteria
Inclusion Criteria:
- Adult participants: Signed informed consent by any participant capable of giving consent, or, where the participant is not capable of giving consent, by his or her legal/authorized representative
- Adolescent participants not able to legally consent: written informed consent for study participation is obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the participant's level of understanding and capability to provide assent
- Participants who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization
- Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT) or reverse transcriptase-polymerase chain reaction (RT-PCR)
- The time interval between the onset of symptoms and randomization is within 96 hours
- A score of ≥4 based on the National Early Warning Score 2 (NEWS2)
- Participants will require objective criteria of seriousness defined by at least one of the following criteria:
- Requires ventilation or supplemental oxygen to support respiration
- Has a complication related to influenza that requires hospitalization (e.g., pneumonia, central nervous system involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, asthma or chronic obstructive pulmonary disease (COPD), severe dehydration, myocarditis, pericarditis, exacerbation of ischemic heart disease)
- For women of childbearing potential: Agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 28 days after the last dose of study treatment. Hormonal contraceptive methods must be supplemented by a barrier method.
Exclusion Criteria:
- Participants who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening
- Participants who have received baloxavir marboxil for the current influenza infection
- Known contraindication to neuraminidase inhibitors
- Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at home)
- Participants expected to die or be discharged within 48 hours, according to the investigator's judgement
- Participants weighing < 40 kg
- Participants with known severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
- Participants with any of the following laboratory abnormalities detected within 24 hours prior to or during screening (according to local laboratory reference ranges:
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) level > 5 times the upper limit of normal (ULN) OR
- ALT or AST > 3 times the ULN and total bilirubin level > 2 times the ULN
- Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment
- Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
- Known hypersensitivity to baloxavir marboxil or the drug product excipients
Sites / Locations
- Torrance Memorial Medical Center
- Denver Health Medical Center
- Atlanta Institute For Medical Research, Inc; DeKalb Medical Pharmacy
- University of Chicago; Oncology Dept
- NorthShore University HealthSystem
- Barnum Medical Research, Inc.
- Detroit Receiving Hospital
- Washington University School of Medicine
- Mercury Street Medical Group
- Creighton University Medical Center
- New York-Presbyterian Brooklyn Methodist Hospital; Department of Emergency Medicine
- Temple University Hospital ; Lung Center
- Salem Veterans Affairs Medical Center - NAVREF; Pharmacy
- Froedtert and The Medical College of Wisconsin
- Instituto Medico Platense
- Royal Brisbane & Womens Hospital; Pharmacy Department
- Royal Children's Hospital Melbourne - PIN
- Hopital Erasme; Chest Medicine, Cardiac & Thoracic Surgery
- Cliniques Universitaires Saint-Luc; Hematology
- UZ Leuven
- Santa Casa de Misericordia; de Belo Horizonte
- Hospital Sao Vicente de Paulo
- Centro de Estudos Clinicos do Interior Paulista
- Multiprofile Hospital For Active Treatment Sveta Ekaterina Dimitrovgrad EOOD; Internal Diseases
- Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases - Haskovo EOOD
- MHAT Stamen Iliev AD; Pharmacy
- University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD; Pharmacy
- Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr. D. Gramatikov - Ruse
- Multiprofile Hospital for Active Treatment - Samokov EOOD
- Multiprofile Hospital For Active Treatment Sliven То Military Hospital Sofia; Pharmacy
- Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD; Pharmacy
- First Multiprofile Hospital for Active Treatment - Sofia EAD
- Fifth Multiprofile Hospital for Active Treatment - Sofia EAD; Pharmacy
- Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia; Pharmacy
- National Multiprofile Transport Hospital Tzar Boris Ill; Clinic of Internal Diseases
- Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD; Pharmacy
- Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases-Vratsa; Pharmacy
- Peter Lougheed Centre
- Foothills Medical Centre
- Carlson Urology
- South Health Campus
- University of Alberta Hospital
- Toronto East General Hospital; Main Pharmacy G Wing Basement
- London Health Sciences Center; Pharmacy Dept.
- Institut Universitaire de Cardiologie et de Pneumologie
- Beijing Youan Hospital, Capital Medical University; Center for Infectious Diseases
- Beijing Ditan Hospital Capital Medical University
- China-Japan Friendship Hospital
- West China Hospital, Sichuan University
- The First Affiliated Hospital of Guangzhou Medical University
- The First Affiliated Hospital of College of Medicine, Zhejiang University
- The 1st Affiliated Hospital of Nanchang Unversity
- Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
- Zhongshan Hospital Fudan University
- Shanghai Public Health Clinical Center
- Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
- Nemocnice Kyjov, prispevkova organizace
- East Tallinn Central Hospital
- Kuopion Yliopistollinen Sairaala; Silmätaudit
- Oulun Yliopistollinen Sairaala; Teho-osasto
- Turku University Hospital
- Centre Hospitalier Victor Dupouy
- CHRU Dijon Complexe Du Bocage
- Centre Hospitalier Departemental de Vendee
- Hôpital Universitaire Dupuytren
- CHRU Nantes
- CHU de Nîmes - Hôpital Carémeau
- Hopital de La Source
- Groupe Hospitalier Pitie Salpetriere; Service De Pneumologie
- Nouvel Hopital Civil - CHU Strasbourg
- CHRU Bretonneau
- Krankenhaus Donaustauf der LVA Niederbayern Oberpfalz
- Universitätsklinikum Carl Gustav Carus an der TU Dresden
- St. Josefskrankenhaus - Freiburg; Klinik fur Pneumologieund Beatmungsmedizin
- Medizinische Hochschule Hannover
- Uniklinik Koln; Klinik I fur Innere Medizin
- Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I
- Klinikum Mannheim GmbH Universitätsklinikum
- Klinikum der Universität Regensburg
- Universitatsklinikum Tubingen
- Princess Margaret Hospital
- Queen Mary Hospital
- Prince of Wales Hospital
- Soroka University Medical Centre
- Edith Wolfson Medical Center
- Galilee Medical Center
- Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit
- Rambam Health Corporation; Oncology Institute
- ZIV Medical Center; Department Of Internal Medicine A
- Tel Aviv Sourasky Medical Center; Pharmacy
- Baruch Padeh Poria Medical Center; Pharmacy
- Fujita General Hospital
- Shin Komonji Hospital
- Fukuoka Shin Mizumaki Hospital
- Fukuoka Wajiro Hospital
- Rinku General Medical Center
- National Hospital Organization Minami Kyoto Hospital
- National Hospital Organization Kanazawa Medical Center
- Japanese Red Cross Kumamoto Hospital
- Naha City Hospital
- National Hospital Organization Ibarakihigashi National Hospital; Center for Clinical Research
- Japan Community Health care Organization Nihonmatsu hospital
- Social Corporation Keigakukai Minamiosaka Hosupital
- National Hospital Organaization Shibukawa Medical Center
- Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
- Saka General Hospital
- Local incorporated administrative agency Shizuoka City Shizuoka Hospital
- Iwase General Hospital
- Center Hospital of the National Center for Global Health and Medicine
- Nagata Hospital; Department of pulmonary medicine
- The Catholic University of Korea Incheon St. Mary's Hospital
- Seoul National University Bundang Hospital
- Korea University Anam Hospital
- Seoul National University Hospital
- Asan Medical Center
- ChungAng University Hospital
- Hallym University Kangnam Sacred Heart Hospital
- Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran; Hamatologia y Oncologia
- Hospital Civil Fray Antonio Alcalde; Instituto de Patologia Infecciosa
- Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas
- Hospital General de Tijuana
- Leids Universitair Medisch Centrum; C5-P Stafcentrum Hartziekten
- Canisius Wilhelmina Ziekenhuis; Department Hematology
- Ikazia Ziekenhuis
- Zuyderland Medisch Centrum - Sittard Geleen
- Universitair Medisch Centrum Utrecht
- Wellington Hospital
- Hospital Alberto Sabogal Sologuren
- Hospital Nacional Adolfo Guevara Velasco - ESSALUD; Servicio de Cardiología
- Prof. Dr. Matei Bals Institute of Infectious Diseases
- Dr. Victor Babes Clinical Hospital For Tropical and Infectious Diseases
- Spitalul Clinic de Boli Infectioase
- Sf.Cuv. Parascheva Infectious Diseases Clinical Hospital
- Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi
- Sibiu Emergency Clinical County Hospital
- Sf. Ioan cel Nou Emergency County Hospital
- Clinical Center of Serbia
- Clinical Hospital Center Zvezdara
- Clinical Center Kragujevac
- Clinical Center Nis; Clinic for Pulmonary Diseases and Tuberculosis Knez Selo
- Clinical Centre of Vojvodina
- General Hospital Dr Radivoj Simonovic Sombor
- Institute of Lung Diseases Vojvodina
- Tan Tock Seng Hospital
- Hospital Universitario Germans Trias i Pujol
- Hospital Sant Joan de Deu - PIN; Unitat de Recerca - Farmacia
- Hospital Mutua de Terrassa
- Hospital Universitario Marques de Valdecilla
- Hospital Universitario de Torrejon
- Hospital General Universitario de Alicante
- Hospital del Mar
- Hospital Universitario Vall d'Hebron - PPDS
- Hospital Universitario Fundacion Jimenez Diaz.
- Hospital General Universitario Reina Sofia; Servicio de Nefrologia
- Hospital Universitario Virgen Macarena
- Hospital de La Ribera
- Sahlgrenska Universitetssjukhuset
- Skånes Universitetssjukhus Malmö; Infektionskliniken
- Hacettepe University Medical Faculty
- Akdeniz University Medical Faculty
- Selcuk University Medical Faculty; Internal Medicine
- Karadeniz Technical University Faculty of Medicine
- Regional Municipal Institution Chernivtsi Regional Clinical Hospital
- Kyiv Oleksandrivska Clinical Hospital; Infectious Box Department #2
- Regional Municipal Institution Sumy Regional Infectious Clinical Hospital n.a. Z.Y. Krasovytskyi
- Ternopil City Municipal Emergency Hospital; Infectious Department
- Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital №1"; Infectious Department
- MI Vinnytsia Regional Clinical Children's Infectious Hospital; Infectiuos Box department
- MI Dnipropetrovsk City Clinical Hospital #21 n.a. Prof. Popkova of DRC; The First Department
- Municipal Institution City Clinical Infectious Diseases Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Baloxavir Marboxil
Placebo
Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.