NCT03684044已完成3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 363
- 试验地点
- 170
- 主要终点
- Time to Clinical Improvement
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Baloxavir Marboxil
Experimental
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.
干预措施: Baloxavir Marboxil (Drug)
Placebo
Placebo Comparator
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.
干预措施: Placebo (Other)
结局指标
主要结局
Time to Clinical Improvement
时间窗: Up to Day 35
Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
次要结局
- Area Under the Curve in Virus Titer(Days 1, 2, 3, 4, 5, 7, and 10)
- Time to Clinical Response(Up to Day 35)
- Duration of Mechanical Ventilation(Up to Day 35)
- Percentage of Participants With Post-Treatment Influenza-Related Complications(Up to Day 35)
- Time to NEWS2 of ≤ 2 Maintained for 24 Hours(Up to Day 35)
- Percentage of Participants on Mechanical Ventilation(Up to Day 35)
- Time to Clinical Failure(Up to Day 35)
- Response Rates of the 6-Point Ordinal Scale at Day 7(Day 7)
- Change From Baseline in Influenza Virus Titer at Each Timepoint(Days 2, 3, 4, 5, 7, and 10)
- Duration of ICU Stay(Up to Day 35)
- Time to Cessation of Viral Shedding by RT-PCR(Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10)
- Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN(Up to Day 35)
- Percentage of Participants Requiring ICU Stay(Up to Day 35)
- Time to Hospital Discharge(Up to Day 35)
- Mortality Rate at Day 7(Up to Day 7)
- Mortality Rate at Day 28(Up to Day 28)
- Time to Cessation of Viral Shedding by Virus Titer(Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10)
- Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint(Days 2, 3, 4, 5, 7, and 10)
- Percentage of Participants Positive by RT-PCR at Each Timepoint(Days 2, 3, 4, 5, 7, and 10)
- Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points(Day 1, 2, 4, 5, 7 and 8)
- Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir(0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8)
- Apparent Half-Life (T1/2) of Baloxavir(0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8)
- Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint(Days 2, 3, 4, 5, 7, and 10)
- Area Under the Curve in the Amount of Virus RNA (RT-PCR)(Days 1, 2, 3, 4, 5, 7, and 10)
- Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment(Up to Day 35)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Day 35)
- Maximum Plasma Concentration (Cmax) of Baloxavir(0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8)
- Concentration at 24 Hours (C24) of Baloxavir(0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8)
研究者
研究点 (170)
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