Clinical trial NCT04464460: A Study to Evaluate the Safety, Pharmacokinetics (PK), and Efficacy of TAK-671 for the Treatment of Coronavirus Disease (COVID) 2019 in Adults
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Coronavirus Disease
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-07-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. Has peripheral capillary SpO2 less than or equal to 93% on room air.
4. 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.
5. Female participants are post-menopausal or surgically sterile.

Exclusion Criteria:

1. Has received TAK-671 or ulinastatin (UTI) in a previous clinical study or as a therapeutic agent.
2. 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.
3. Has evidence of multiorgan failure, based on a SOFA score greater than 12.
4. Is on invasive mechanical ventilation.
5. Requires vasopressor support. (However, use of fluid support is not exclusionary.)
6. Has known or suspected venous thromboembolism.
7. Any female participant who is of child-bearing potential or is breastfeeding.
8. Has active tuberculosis or a clinical suspicion of latent tuberculosis.
9. Has fulminant hepatic or renal failure.
10. 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).
11. 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.
12. Has a life expectancy of less than 6 months due to reasons other than COVID-19 in the opinion of the investigator.
13. Has a do-not-resuscitate or do-not-intubate (DNR/DNI) order.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 28
measure: Number of Participants With Markedly Abnormal Laboratory Values
timeFrame: Baseline up to Day 28
measure: Number of Participants With Markedly Abnormal Values of Vital Signs
timeFrame: Baseline up to Day 28
measure: Number of Participants With Markedly Abnormal 12-lead Electrocardiograms
timeFrame: Baseline up to Day 28
measure: Number of Participants With Adverse Events (AEs) Related to Physical Examination Findings
timeFrame: Baseline up to Day 28
measure: Ceoi: Serum Concentration at the end of Infusion for TAK-671
timeFrame: Day 14: at the end of infusion (at 336 hours post infusion)
measure: T1/2z: Terminal Disposition Serum Half-life for TAK-671
timeFrame: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
measure: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-671
timeFrame: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
measure: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-671
timeFrame: Day 0 pre-infusion and at multiple time points (up to 336 hours) post-infusion
Secondary outcomes:
measure: Percentage of Participants With Sustained Clinical Improvement or Live Discharge at Day 28
timeFrame: Day 28
measure: Percentage of Participants With Sustained Clinical Recovery
timeFrame: Up to 28 days
measure: Percentage of Participants With Sustained Remission of Respiratory Symptoms
timeFrame: Up to 28 days
measure: Mortality Rate
timeFrame: Up to 28 days
measure: Time to Sustained Clinical Improvement or Discharge From Hospital
timeFrame: Up to 28 days
measure: Time to Sustained Clinical Recovery
timeFrame: Up to 28 days
measure: Percentage of Participants With Any Form of New Ventilation Use
timeFrame: Up to 28 days
measure: Number of Days of New Ventilation Use
timeFrame: Up to 28 days
measure: Number of Ventilation-free Days
timeFrame: Up to 28 days
measure: Number of Days Free of Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)
timeFrame: Up to 28 days
measure: Time to Sustained Remission of Respiratory Symptoms
timeFrame: Up to 28 days
measure: Percentage of Participants Admitted to Intensive Care Unit (ICU)
timeFrame: Up to 28 days
measure: Number of Days of ICU Stay
timeFrame: Up to 28 days
measure: Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Days 7, 14, and 28
timeFrame: Baseline, Days 7, 14, and 28
Other outcomes:
Locations:
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: