A Study to Evaluate the Safety, Pharmacokinetics (PK), and Efficacy of TAK-671 for the Treatment of Coronavirus Disease (COVID) 2019 in Adults

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess safety, tolerability, preliminary efficacy, and PK of TAK-671 in participants with COVID-19.

Detailed Description
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Coronavirus Disease

Intervention / Treatment
-----------------
* Drug: TAK-671
* Drug: TAK-671 Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Exclusion Criteria: 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 12. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TAK-671 Low Dose<br>TAK-671 low dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1. | Drug: TAK-671<br>* TAK-671 intravenous infusion.<br>* Other names: SB26;Drug: TAK-671 Placebo<br>* TAK-671 placebo-matching intravenous infusion.<br>* Other names: SB26/TAK-671 matching-placebo;|
| Experimental: Cohort 2: TAK-671 High Dose<br>TAK-671 high dose or TAK-671 placebo-matching, infusion over a 90-minute period, intravenously, once on Day 1. | Drug: TAK-671<br>* TAK-671 intravenous infusion.<br>* Other names: SB26;Drug: TAK-671 Placebo<br>* TAK-671 placebo-matching intravenous infusion.<br>* Other names: SB26/TAK-671 matching-placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |  | Baseline up to Day 28 | 
| Number of Participants With Markedly Abnormal Laboratory Values |  | Baseline up to Day 28 | 
| Number of Participants With Markedly Abnormal Values of Vital Signs |  | Baseline up to Day 28 | 
| Number of Participants With Markedly Abnormal 12-lead Electrocardiograms |  | Baseline up to Day 28 | 
| Number of Participants With Adverse Events (AEs) Related to Physical Examination Findings |  | Baseline up to Day 28 | 
| Ceoi: Serum Concentration at the end of Infusion for TAK-671 |  | Day 14: at the end of infusion (at 336 hours post infusion) | 
| T1/2z: Terminal Disposition Serum Half-life for TAK-671 |  | Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion | 
| AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-671 |  | 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 |  | Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Clinical Improvement or Live Discharge at Day 28 | Sustained clinical improvement is defined as a 2-point improvement on the 8-point ordinal scale for clinical improvement, that is at least 2 points increase from the lowest score recorded since randomization and no worsening of the score afterwards by Day 28. An 8-point ordinal scale for clinical improvement in COVID-19 symptoms ranges from a score of 1 to a score of 8, where 1 (death), 2 (hospitalized, on invasive mechanical ventilation or ECMO), 3 (hospitalized, on non-invasive ventilation or high-flow oxygen devices), 4 (hospitalized, requiring supplemental oxygen), 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care [COVID-19 related or otherwise]), 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), and 8 (not hospitalized, no limitations on activities). | Day 28 | 
| Percentage of Participants With Sustained Clinical Recovery | Sustained clinical recovery is defined as achieving score 6, 7, or 8 based on the ordinal scale and maintained the clinical recovery until Day 28. An 8-point ordinal scale for clinical improvement in COVID-19 symptoms ranges from a score of 1 to a score of 8, where 1 (death), 2 (hospitalized, on invasive mechanical ventilation or ECMO), 3 (hospitalized, on non-invasive ventilation or high-flow oxygen devices), 4 (hospitalized, requiring supplemental oxygen), 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care [COVID-19 related or otherwise]), 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), and 8 (not hospitalized, no limitations on activities). | Up to 28 days | 
| Percentage of Participants With Sustained Remission of Respiratory Symptoms | Sustained remission of respiratory symptoms is defined as independence from supplemental oxygen therapy in order to maintain oxygen saturation (SpO2) greater than 94 percent (%) and is maintained up to Day 28. | Up to 28 days | 
| Mortality Rate |  | Up to 28 days | 
| Time to Sustained Clinical Improvement or Discharge From Hospital | Sustained clinical improvement is defined as a 2-point improvement on the 8-point ordinal scale for clinical improvement, that is at least 2 points increase from the lowest score recorded since randomization and no worsening of the score afterwards by Day 28. An 8-point ordinal scale for clinical improvement in COVID-19 symptoms ranges from a score of 1 to a score of 8, where 1 (death), 2 (hospitalized, on invasive mechanical ventilation or ECMO), 3 (hospitalized, on non-invasive ventilation or high-flow oxygen devices), 4 (hospitalized, requiring supplemental oxygen), 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care [COVID-19 related or otherwise]), 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), and 8 (not hospitalized, no limitations on activities). | Up to 28 days | 
| Time to Sustained Clinical Recovery | Sustained clinical recovery is defined as achieving score 6, 7, or 8 based on the ordinal scale and maintained the clinical recovery until Day 28. An 8-point ordinal scale for clinical improvement in COVID-19 symptoms ranges from a score of 1 to a score of 8, where 1 (death), 2 (hospitalized, on invasive mechanical ventilation or ECMO), 3 (hospitalized, on non-invasive ventilation or high-flow oxygen devices), 4 (hospitalized, requiring supplemental oxygen), 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care [COVID-19 related or otherwise]), 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), and 8 (not hospitalized, no limitations on activities). | Up to 28 days | 
| Percentage of Participants With Any Form of New Ventilation Use |  | Up to 28 days | 
| Number of Days of New Ventilation Use |  | Up to 28 days | 
| Number of Ventilation-free Days |  | 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 | Remission of respiratory symptoms is defined as independence from supplemental oxygen therapy in order to maintain SpO2 greater than 94%. | 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 | The SOFA score is a scale for describing multiple organ failure in the critical care setting. It is calculated using the functional status of several organ systems: respiratory, coagulation, liver, cardiovascular, central nervous system, and renal. Each of these organ systems is rated on a scale of 1 to 4, based on objective, testable criteria, chiefly laboratory values. The ratings of each of these systems (worse observed value during that 24-hour period) are then summed to create the total score. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). The minimum score is 0, the maximum score is 24, with higher scores indicating higher likelihood of worse outcome. | Baseline, Days 7, 14, and 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy