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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03684044




Registration number
NCT03684044
Ethics application status
Date submitted
24/09/2018
Date registered
25/09/2018

Titles & IDs
Public title
Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
Scientific title
A Phase III, Randomized, Double-Blind Placebo-Controlled, Multicenter Study To Evaluate the Efficacy and Safety of Baloxavir Marboxil in Combination With Standard-of-Care Neuraminidase Inhibitor in Hospitalized Participants With Severe Influenza
Secondary ID [1] 0 0
2018-001416-30
Secondary ID [2] 0 0
CP40617
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Baloxavir Marboxil
Other interventions - Placebo

Experimental: Baloxavir Marboxil - 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.

Placebo comparator: Placebo - 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.


Treatment: Drugs: Baloxavir Marboxil
Baloxavir marboxil will be administered as a weight-based dose on Days 1 and 4. A third dose will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5.

Other interventions: Placebo
Participants will receive matching placebo on Days 1, 4 and 7.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Clinical Improvement
Timepoint [1] 0 0
Up to Day 35
Secondary outcome [1] 0 0
Response Rates of the 6-Point Ordinal Scale at Day 7
Timepoint [1] 0 0
Day 7
Secondary outcome [2] 0 0
Time to Clinical Response
Timepoint [2] 0 0
Up to Day 35
Secondary outcome [3] 0 0
Percentage of Participants on Mechanical Ventilation
Timepoint [3] 0 0
Up to Day 35
Secondary outcome [4] 0 0
Duration of Mechanical Ventilation
Timepoint [4] 0 0
Up to Day 35
Secondary outcome [5] 0 0
Percentage of Participants Requiring ICU Stay
Timepoint [5] 0 0
Up to Day 35
Secondary outcome [6] 0 0
Duration of ICU Stay
Timepoint [6] 0 0
Up to Day 35
Secondary outcome [7] 0 0
Time to Clinical Failure
Timepoint [7] 0 0
Up to Day 35
Secondary outcome [8] 0 0
Time to Hospital Discharge
Timepoint [8] 0 0
Up to Day 35
Secondary outcome [9] 0 0
Percentage of Participants With Post-Treatment Influenza-Related Complications
Timepoint [9] 0 0
Up to Day 35
Secondary outcome [10] 0 0
Mortality Rate at Day 7
Timepoint [10] 0 0
Up to Day 7
Secondary outcome [11] 0 0
Mortality Rate at Day 28
Timepoint [11] 0 0
Up to Day 28
Secondary outcome [12] 0 0
Time to NEWS2 of = 2 Maintained for 24 Hours
Timepoint [12] 0 0
Up to Day 35
Secondary outcome [13] 0 0
Time to Cessation of Viral Shedding by Virus Titer
Timepoint [13] 0 0
Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10
Secondary outcome [14] 0 0
Change From Baseline in Influenza Virus Titer at Each Timepoint
Timepoint [14] 0 0
Days 2, 3, 4, 5, 7, and 10
Secondary outcome [15] 0 0
Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint
Timepoint [15] 0 0
Days 2, 3, 4, 5, 7, and 10
Secondary outcome [16] 0 0
Area Under the Curve in Virus Titer
Timepoint [16] 0 0
Days 1, 2, 3, 4, 5, 7, and 10
Secondary outcome [17] 0 0
Time to Cessation of Viral Shedding by RT-PCR
Timepoint [17] 0 0
Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10
Secondary outcome [18] 0 0
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint
Timepoint [18] 0 0
Days 2, 3, 4, 5, 7, and 10
Secondary outcome [19] 0 0
Percentage of Participants Positive by RT-PCR at Each Timepoint
Timepoint [19] 0 0
Days 2, 3, 4, 5, 7, and 10
Secondary outcome [20] 0 0
Area Under the Curve in the Amount of Virus RNA (RT-PCR)
Timepoint [20] 0 0
Days 1, 2, 3, 4, 5, 7, and 10
Secondary outcome [21] 0 0
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [21] 0 0
Up to Day 35
Secondary outcome [22] 0 0
Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment
Timepoint [22] 0 0
Up to Day 35
Secondary outcome [23] 0 0
Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN
Timepoint [23] 0 0
Up to Day 35
Secondary outcome [24] 0 0
Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points
Timepoint [24] 0 0
Day 1, 2, 4, 5, 7 and 8
Secondary outcome [25] 0 0
Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir
Timepoint [25] 0 0
0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary outcome [26] 0 0
Maximum Plasma Concentration (Cmax) of Baloxavir
Timepoint [26] 0 0
0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary outcome [27] 0 0
Apparent Half-Life (T1/2) of Baloxavir
Timepoint [27] 0 0
0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary outcome [28] 0 0
Concentration at 24 Hours (C24) of Baloxavir
Timepoint [28] 0 0
0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane & Womens Hospital; Pharmacy Department - Herston
Recruitment hospital [2] 0 0
Royal Children's Hospital Melbourne - PIN - Parkville
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Montana
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Argentina
State/province [14] 0 0
La Plata
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Brazil
State/province [17] 0 0
MG
Country [18] 0 0
Brazil
State/province [18] 0 0
RS
Country [19] 0 0
Brazil
State/province [19] 0 0
SP
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Dimitrovgrad
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Haskovo
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Montana
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Plovdiv
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Ruse
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Samokov
Country [26] 0 0
Bulgaria
State/province [26] 0 0
Sliven
Country [27] 0 0
Bulgaria
State/province [27] 0 0
Smolyan
Country [28] 0 0
Bulgaria
State/province [28] 0 0
Sofia
Country [29] 0 0
Bulgaria
State/province [29] 0 0
Veliko Tarnovo
Country [30] 0 0
Bulgaria
State/province [30] 0 0
Vratsa
Country [31] 0 0
Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
China
State/province [34] 0 0
Beijing City
Country [35] 0 0
China
State/province [35] 0 0
Beijing
Country [36] 0 0
China
State/province [36] 0 0
Chengdu
Country [37] 0 0
China
State/province [37] 0 0
Guangzhou
Country [38] 0 0
China
State/province [38] 0 0
Hangzhou
Country [39] 0 0
China
State/province [39] 0 0
Nanchang
Country [40] 0 0
China
State/province [40] 0 0
Shanghai
Country [41] 0 0
Czechia
State/province [41] 0 0
Brno
Country [42] 0 0
Czechia
State/province [42] 0 0
Kyjov
Country [43] 0 0
Estonia
State/province [43] 0 0
Tallinn
Country [44] 0 0
Finland
State/province [44] 0 0
Kuopio
Country [45] 0 0
Finland
State/province [45] 0 0
Oulu
Country [46] 0 0
Finland
State/province [46] 0 0
Turku
Country [47] 0 0
France
State/province [47] 0 0
Argenteuil
Country [48] 0 0
France
State/province [48] 0 0
Dijon
Country [49] 0 0
France
State/province [49] 0 0
La Roche Sur Yon
Country [50] 0 0
France
State/province [50] 0 0
Limoges
Country [51] 0 0
France
State/province [51] 0 0
Nantes
Country [52] 0 0
France
State/province [52] 0 0
Nimes
Country [53] 0 0
France
State/province [53] 0 0
Orleans
Country [54] 0 0
France
State/province [54] 0 0
Paris
Country [55] 0 0
France
State/province [55] 0 0
Strasbourg
Country [56] 0 0
France
State/province [56] 0 0
Tours
Country [57] 0 0
Germany
State/province [57] 0 0
Donaustauf
Country [58] 0 0
Germany
State/province [58] 0 0
Dresden
Country [59] 0 0
Germany
State/province [59] 0 0
Freiburg im Breisgau
Country [60] 0 0
Germany
State/province [60] 0 0
Hannover
Country [61] 0 0
Germany
State/province [61] 0 0
Köln
Country [62] 0 0
Germany
State/province [62] 0 0
Lubeck
Country [63] 0 0
Germany
State/province [63] 0 0
Mannheim
Country [64] 0 0
Germany
State/province [64] 0 0
Regensburg
Country [65] 0 0
Germany
State/province [65] 0 0
Tübingen
Country [66] 0 0
Hong Kong
State/province [66] 0 0
Hong Kong
Country [67] 0 0
Hong Kong
State/province [67] 0 0
Shatin, New Territories
Country [68] 0 0
Israel
State/province [68] 0 0
Beer Sheva
Country [69] 0 0
Israel
State/province [69] 0 0
Holon
Country [70] 0 0
Israel
State/province [70] 0 0
Nahariya
Country [71] 0 0
Israel
State/province [71] 0 0
Ramat Gan
Country [72] 0 0
Israel
State/province [72] 0 0
Rambam
Country [73] 0 0
Israel
State/province [73] 0 0
Safed
Country [74] 0 0
Israel
State/province [74] 0 0
Tel Aviv
Country [75] 0 0
Israel
State/province [75] 0 0
Tiberias
Country [76] 0 0
Japan
State/province [76] 0 0
Dategun Kunimimachi
Country [77] 0 0
Japan
State/province [77] 0 0
Fukuoka
Country [78] 0 0
Japan
State/province [78] 0 0
Izumisano
Country [79] 0 0
Japan
State/province [79] 0 0
Joyo
Country [80] 0 0
Japan
State/province [80] 0 0
Kanazawa
Country [81] 0 0
Japan
State/province [81] 0 0
Kumamoto-shi
Country [82] 0 0
Japan
State/province [82] 0 0
Naha
Country [83] 0 0
Japan
State/province [83] 0 0
Naka-gun
Country [84] 0 0
Japan
State/province [84] 0 0
Nihonmatsu
Country [85] 0 0
Japan
State/province [85] 0 0
Osaka
Country [86] 0 0
Japan
State/province [86] 0 0
Shibukawa
Country [87] 0 0
Japan
State/province [87] 0 0
Shinagawa
Country [88] 0 0
Japan
State/province [88] 0 0
Shiogama
Country [89] 0 0
Japan
State/province [89] 0 0
Shizuoka
Country [90] 0 0
Japan
State/province [90] 0 0
Sukagawa
Country [91] 0 0
Japan
State/province [91] 0 0
Tokyo
Country [92] 0 0
Japan
State/province [92] 0 0
Yanagawa-shi
Country [93] 0 0
Korea, Republic of
State/province [93] 0 0
Incheon
Country [94] 0 0
Korea, Republic of
State/province [94] 0 0
Seongnam-si
Country [95] 0 0
Korea, Republic of
State/province [95] 0 0
Seoul
Country [96] 0 0
Mexico
State/province [96] 0 0
Mexico CITY (federal District)
Country [97] 0 0
Mexico
State/province [97] 0 0
Guadalajara
Country [98] 0 0
Mexico
State/province [98] 0 0
Monterrey
Country [99] 0 0
Mexico
State/province [99] 0 0
Tijuana
Country [100] 0 0
Netherlands
State/province [100] 0 0
Leiden
Country [101] 0 0
Netherlands
State/province [101] 0 0
Nijmegen
Country [102] 0 0
Netherlands
State/province [102] 0 0
Rotterdam
Country [103] 0 0
Netherlands
State/province [103] 0 0
Sittard-Geleen
Country [104] 0 0
Netherlands
State/province [104] 0 0
Utrecht
Country [105] 0 0
New Zealand
State/province [105] 0 0
Wellington
Country [106] 0 0
Peru
State/province [106] 0 0
Callao
Country [107] 0 0
Peru
State/province [107] 0 0
Cusco
Country [108] 0 0
Romania
State/province [108] 0 0
Bucharest
Country [109] 0 0
Romania
State/province [109] 0 0
Cluj Napoca
Country [110] 0 0
Romania
State/province [110] 0 0
Galati
Country [111] 0 0
Romania
State/province [111] 0 0
Iasi
Country [112] 0 0
Romania
State/province [112] 0 0
Sibiu
Country [113] 0 0
Romania
State/province [113] 0 0
Suceava
Country [114] 0 0
Serbia
State/province [114] 0 0
Belgrade
Country [115] 0 0
Serbia
State/province [115] 0 0
Kragujevac
Country [116] 0 0
Serbia
State/province [116] 0 0
Nis
Country [117] 0 0
Serbia
State/province [117] 0 0
Nova Sad
Country [118] 0 0
Serbia
State/province [118] 0 0
Sombor
Country [119] 0 0
Serbia
State/province [119] 0 0
Sremska Kamenica
Country [120] 0 0
Singapore
State/province [120] 0 0
Singapore
Country [121] 0 0
Spain
State/province [121] 0 0
Barcelona
Country [122] 0 0
Spain
State/province [122] 0 0
Cantabria
Country [123] 0 0
Spain
State/province [123] 0 0
Madrid
Country [124] 0 0
Spain
State/province [124] 0 0
Alicante
Country [125] 0 0
Spain
State/province [125] 0 0
Murcia
Country [126] 0 0
Spain
State/province [126] 0 0
Sevilla
Country [127] 0 0
Spain
State/province [127] 0 0
Valencia
Country [128] 0 0
Sweden
State/province [128] 0 0
Goteborg
Country [129] 0 0
Sweden
State/province [129] 0 0
Malmö
Country [130] 0 0
Turkey
State/province [130] 0 0
Ankara
Country [131] 0 0
Turkey
State/province [131] 0 0
Antalya
Country [132] 0 0
Turkey
State/province [132] 0 0
Konya
Country [133] 0 0
Turkey
State/province [133] 0 0
Trabzon
Country [134] 0 0
Ukraine
State/province [134] 0 0
Chernihiv Governorate
Country [135] 0 0
Ukraine
State/province [135] 0 0
Katerynoslav Governorate
Country [136] 0 0
Ukraine
State/province [136] 0 0
KIEV Governorate
Country [137] 0 0
Ukraine
State/province [137] 0 0
Podolia Governorate
Country [138] 0 0
Ukraine
State/province [138] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.