Phase 3
Completed N=363
Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
Source: ClinicalTrials.gov NCT03684044 ↗Enrolled (actual)
363
Serious AEs
13.2%
Results posted
Nov 2020
Primary outcomePrimary: Time to Clinical Improvement — 97.5; 100.2 hours — p=0.4666
◆ Published Evidence
Highly cited
135citations · ~27 / year
The place for remdesivir in COVID-19 treatment.
Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of baloxavir marboxil in combination with a standard-of-care (SOC) neuraminidase inhibitor (NAI) (i.e., oseltamivir, zanamivir, or peramivir) compared with a matching placebo in combination with a SOC NAI in hospitalized patients with influenza.
Linked Publications (3)
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The place for remdesivir in COVID-19 treatment.
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Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial.
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Assessing the fitness of a dual-antiviral drug resistant human influenza virus in the ferret model.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Clinical Improvement |
97.5; 100.2 | 0.4666 |
| SECONDARY Response Rates of the 6-Point Ordinal Scale at Day 7 |
49.2; 45.4; 22.6; 24.1; 20.1; 22.2 | 0.6326 |
| SECONDARY Time to Clinical Response |
138.3; 145.1 | 0.3272 |
| SECONDARY Percentage of Participants on Mechanical Ventilation |
5.3; 6.1 | — |
| SECONDARY Duration of Mechanical Ventilation |
150.25; 91.00 | — |
| SECONDARY Percentage of Participants Requiring ICU Stay |
4.3; 3.5 | — |
| SECONDARY Duration of ICU Stay |
138.55; 71.78 | — |
| SECONDARY Time to Clinical Failure |
NA; NA | — |
| SECONDARY Time to Hospital Discharge |
166.7; 167.3 | — |
| SECONDARY Percentage of Participants With Post-Treatment Influenza-Related Complications |
10.6; 14.0 | — |
| SECONDARY Mortality Rate at Day 7 |
0.5; 2.6 | — |
| SECONDARY Mortality Rate at Day 28 |
1.9; 5.3 | — |
| SECONDARY Time to NEWS2 of ≤ 2 Maintained for 24 Hours |
106.3; 127.2 | — |
| SECONDARY Time to Cessation of Viral Shedding by Virus Titer |
23.9; 63.7 | — |
| SECONDARY Change From Baseline in Influenza Virus Titer at Each Timepoint |
-2.36; -1.00; -2.70; -1.93; -2.88; -2.50 | — |
| SECONDARY Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint |
37.7; 80.3; 18.6; 53.4; 7.9; 26.7 | — |
| SECONDARY Area Under the Curve in Virus Titer |
291.68; 332.04 | — |
| SECONDARY Time to Cessation of Viral Shedding by RT-PCR |
216.3; 261.1 | — |
| SECONDARY Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint |
-0.98; -0.66; -1.54; -1.19; -2.35; -1.84 | — |
| SECONDARY Percentage of Participants Positive by RT-PCR at Each Timepoint |
95.6; 96.3; 90.0; 93.3; 88.1; 87.9 | — |
| SECONDARY Area Under the Curve in the Amount of Virus RNA (RT-PCR) |
676.40; 740.15 | — |
| SECONDARY Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
45.2; 50.0; 12.1; 15.3 | — |
| SECONDARY Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment |
1.3; 3.2; 0.8; 1.6 | — |
| SECONDARY Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN |
4.6; 8.9; 0.8; 3.2; 0; 1.6 | — |
| SECONDARY Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points |
37.82; 75.06; 95.85; 64.47; 53.36; 24.26 | — |
| SECONDARY Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir |
2820; 3170 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Baloxavir |
86.3; 123 | — |
| SECONDARY Apparent Half-Life (T1/2) of Baloxavir |
18.9; 23.4 | — |
| SECONDARY Concentration at 24 Hours (C24) of Baloxavir |
43.9; 67.1; 105 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT03684044) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.