A Randomized, Double-blind, Placebo-Controlled Multicenter Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of 2 Different Intravenous Doses of TAK-671 for the Treatment of Coronavirus Disease 2019 in Adults
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Number of Participants With Markedly Abnormal Laboratory Values
研究概览
简要总结
The purpose of this study is to assess safety, tolerability, preliminary efficacy, and PK of TAK-671 in participants with COVID-19.
详细描述
The drug being tested in this study is called TAK-671. The study will evaluate the safety, tolerability and PK of TAK-671 in participants admitted to the hospital with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test.
The study will enroll approximately 40 participants. Each cohort will have 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) in a 3:1 ratio to receive TAK-671 or placebo in each cohort, which will remain undisclosed to the participant during the study (unless there is an urgent medical need):
- Cohort 1: TAK-671 Low Dose
- Cohort 2: TAK-671 High Dose
Enrollment in Cohort 2 will only begin once all 20 participants in Cohort 1 have reached Day 7 post dose and have received positive review from the internal review committee (IRC) and approval to continue enrollment. All participants will receive the standard of care along with the study treatment.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 3 months. All participants will be followed up 28 days after the infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has laboratory-confirmed SARS-CoV-2 infection as determined via polymerase chain reaction or an accepted molecular assay of any specimen, example, respiratory, blood, urine, stool, other body fluid.
- •It has been less than 72 hours since time of the participant's hospital admission, or, if hospital acquired COVID-19 is confirmed, less than 72 hours after confirmation of positive SARS-CoV-2 test or the onset of respiratory symptoms, whichever is first.
- •Has peripheral capillary SpO2 less than or equal to 93% on room air.
- •Weighs greater than or equal to (>=) 50 kilogram (kg) and has a body mass index (BMI) 18 to 35 kilogram per square meter (kg/m^2), inclusive.
- •Female participants are post-menopausal or surgically sterile.
排除标准
- •Has received TAK-671 or ulinastatin (UTI) in a previous clinical study or as a therapeutic agent.
- •Has received a human blood product (other than a transfusion needed for trauma treatment) or has been treated with a monoclonal antibody or Fc-fusion biologic within 5 years of the screening visit.
- •Has evidence of multiorgan failure, based on a SOFA score greater than
- •Is on invasive mechanical ventilation.
- •Requires vasopressor support. (However, use of fluid support is not exclusionary.)
- •Has known or suspected venous thromboembolism.
- •Any female participant who is of child-bearing potential or is breastfeeding.
- •Has active tuberculosis or a clinical suspicion of latent tuberculosis.
- •Has fulminant hepatic or renal failure.
- •Has congestive heart failure of New York Heart Association Grade III or IV, pulmonary embolism, or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy).
- •Participant's progression to death is imminent and inevitable within the next 24 hours, regardless of cause and irrespective of the provision of treatments, in the opinion of the investigator.
- •Has a life expectancy of less than 6 months due to reasons other than COVID-19 in the opinion of the investigator.
- •Has a do-not-resuscitate or do-not-intubate (DNR/DNI) order.
研究组 & 干预措施
Cohort 1: TAK-671 Low Dose
TAK-671 low dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1.
干预措施: TAK-671 (Drug)
Cohort 1: TAK-671 Low Dose
TAK-671 low dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1.
干预措施: TAK-671 Placebo (Drug)
Cohort 2: TAK-671 High Dose
TAK-671 high dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1.
干预措施: TAK-671 (Drug)
Cohort 2: TAK-671 High Dose
TAK-671 high dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1.
干预措施: TAK-671 Placebo (Drug)
结局指标
主要结局
Number of Participants With Markedly Abnormal Laboratory Values
时间窗: Baseline up to Day 28
Number of Participants With Markedly Abnormal 12-lead Electrocardiograms
时间窗: Baseline up to Day 28
AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-671
时间窗: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-671
时间窗: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline up to Day 28
Number of Participants With Markedly Abnormal Values of Vital Signs
时间窗: Baseline up to Day 28
Number of Participants With Adverse Events (AEs) Related to Physical Examination Findings
时间窗: Baseline up to Day 28
Ceoi: Serum Concentration at the end of Infusion for TAK-671
时间窗: Day 14: at the end of infusion (at 336 hours post infusion)
T1/2z: Terminal Disposition Serum Half-life for TAK-671
时间窗: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
次要结局
- Percentage of Participants With Sustained Clinical Improvement or Live Discharge at Day 28(Day 28)
- Percentage of Participants With Sustained Clinical Recovery(Up to 28 days)
- Percentage of Participants With Any Form of New Ventilation Use(Up to 28 days)
- Number of Ventilation-free Days(Up to 28 days)
- Percentage of Participants With Sustained Remission of Respiratory Symptoms(Up to 28 days)
- Mortality Rate(Up to 28 days)
- Time to Sustained Clinical Improvement or Discharge From Hospital(Up to 28 days)
- Time to Sustained Clinical Recovery(Up to 28 days)
- Number of Days of New Ventilation Use(Up to 28 days)
- Number of Days Free of Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)(Up to 28 days)
- Time to Sustained Remission of Respiratory Symptoms(Up to 28 days)
- Percentage of Participants Admitted to Intensive Care Unit (ICU)(Up to 28 days)
- Number of Days of ICU Stay(Up to 28 days)
- Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Days 7, 14, and 28(Baseline, Days 7, 14, and 28)