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ACTIV-5 / Big Effect Trial (BET-B) for the Treatment of COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04583969
Recruitment Status : Completed
First Posted : October 12, 2020
Results First Posted : June 5, 2023
Last Update Posted : June 5, 2023
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
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Brief Summary:

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: Lenzilumab Other: Placebo Drug: Remdesivir Phase 2

Detailed Description:

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with Coronavirus Disease 2019 (COVID-19). Big Effect Trial (BET) is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention.

The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses.

One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once.

The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.

The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8. The key secondary objectives are to 1) evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.

Contacts:

20-0013 Central Contact

Telephone: 1 (301) 7617948

Email: DMIDClinicalTrials@niaid.nih.gov

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 527 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Actual Study Start Date : October 23, 2020
Actual Primary Completion Date : April 22, 2022
Actual Study Completion Date : April 22, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Remdesivir + Lenzilumab
200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 600-mg IV lenzilumab infusion every 8 hours starting on Day 1 for a total of 3 doses. N=275.
 Biological: Lenzilumab
Lenzilumab is a first-in-class recombinant monoclonal antibody targeting soluble human GM-CSF, with potential immunomodulating activity, high binding affinity in the pM range, and 94% specificity to the human germline, which reduces immunogenicity.

Drug: Remdesivir
Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Active Comparator: Remdesivir + Placebo
200-mg intravenous (IV) remdesivir loading dose on Day 1, followed by a 100-mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 600-mg IV lenzilumab placebo infusion every 8 hours starting on Day 1 for a total of 3 doses. N=275.
 Other: Placebo
Placebo for lenzilumab is commercially sourced 0.9% sodium chloride.

Drug: Remdesivir
Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524.


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years [ Time Frame: Day 1 through Day 29 ]
    Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.


Secondary Outcome Measures :
  1. Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score [ Time Frame: Day 1 through Day 29 ]
    Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.

  2. Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years [ Time Frame: Day 1 through Day 60 ]
    Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, Continuous Positive Airway Pressure (CPAP), or Bilevel Positive Airway Pressure (BiPAP); 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.

  3. Time to Sustained Recovery in Participants With Any Baseline Ordinal Score [ Time Frame: Day 1 through Day 60 ]
    Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.

  4. Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 [ Time Frame: Day 8 ]
    The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death

  5. Change From Baseline in C-Reactive Protein (CRP) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  6. Change From Baseline in D-dimer [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  7. Change From Baseline in Ferritin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  8. Change From Baseline in Fibrinogen [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  9. Change From Baseline in Alanine Aminotransferase (ALT) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  10. Change From Baseline in Aspartate Transaminase (AST) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  11. Change From Baseline in Creatinine [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  12. Change From Baseline in International Normalized Ratio (INR) [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  13. Change From Baseline in Hemoglobin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  14. Change From Baseline in Platelets Count [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  15. Change From Baseline in Total Bilirubin [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  16. Change From Baseline in White Blood Cell (WBC) Count [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  17. Change From Baseline in Neutrophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  18. Change From Baseline in Eosinophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  19. Change From Baseline in Basophils [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  20. Change From Baseline in Lymphocytes [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.

  21. Change From Baseline in Monocytes [ Time Frame: Days 1, 3, 5, 8, 11, 15, 29 ]
    Blood was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.

  22. Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs) [ Time Frame: Day 1 through Day 60 ]
    Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening while Grade 5 AEs are those that are fatal. Laboratory results were considered AEs if they were grade 3 or above according to the thresholds in the Division of AIDS (DAIDS) Table for Grading the Severity of Adverse Events.

  23. Number of Participants Reporting Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 60 ]
    An SAE is defined as an AE or suspected adverse reaction that is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

  24. Number of Participants Who Discontinued or Temporarily Suspended Study Treatment [ Time Frame: Day 1 through Day 29 ]
    Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.

  25. Duration of Hospitalization [ Time Frame: Day 1 through Day 29 ]
    Duration of hospitalization is defined first as the total number of days hospitalized for COVID-19, including readmissions for COVID-19-related reasons. It is also calculated as the total number of days hospitalized, including any readmissions for any reason.

  26. Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.

  27. Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    Duration of new invasive mechanical ventilation/ECMO use was measured in days among participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died.

  28. Days of Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of non-invasive ventilation or high flow oxygen use was measured in days among participants who required non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.

  29. Days of New Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants not on non-invasive ventilation/high flow oxygen at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.

  30. Days of Supplemental Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    Duration of supplemental oxygen use was measured in days among participants who required any supplemental oxygen, non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.

  31. Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use [ Time Frame: Day 1 through Day 29 ]
    New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use is defined as participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died during the study.

  32. Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use [ Time Frame: Day 1 through Day 29 ]
    New Non-invasive Ventilation/High Flow Oxygen Use is defined as participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline who progressed to noninvasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study.

  33. Mean Change in Ordinal Scale [ Time Frame: Days 1, 3, 5, 8, 11, 15, 22, 29 ]
    The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities;2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement.

  34. 14-day Participant Mortality [ Time Frame: Day 1 through Day 15 ]
    The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.

  35. 28-day Participant Mortality [ Time Frame: Day 1 through Day 29 ]
    The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.

  36. 59-day Participant Mortality [ Time Frame: Day 1 through Day 60 ]
    The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.

  37. Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29 [ Time Frame: Day 29 ]
    Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit.

  38. Time to an Improvement of One Category From Baseline Using an Ordinal Scale [ Time Frame: Day 1 through Day 60 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

  39. Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale [ Time Frame: Day 1 through Day 60 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

  40. Time to Death [ Time Frame: Day 1 through Day 29 ]
    The time to death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
  2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
  3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
  4. Male or non-pregnant female adult >/= 18 years of age at time of enrollment.
  5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) in any respiratory specimen, or saliva </=14 days prior to randomization.
  6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).

  7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception* from the time of screening through 5 months post study intraperitoneal (IP) dosing.

    * Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.

  8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.

Exclusion Criteria:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal.

  2. Subjects with a low glomerular filtration rate (eGFR), specifically:

    1. Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
    2. All subjects with a glomerular filtration rate (eGFR) <20 mL/min (including hemodialysis and hemofiltration) are excluded.
  3. Pregnancy or breast feeding.
  4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
  5. Allergy to any study medication.
  6. Received five or more doses of remdesivir prior to screening.
  7. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
  8. Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 [e.g., anakinra, canakinumab], anti-IL-6 [e.g., tocilizumab, sarilumab, sitlukimab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
  9. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
  10. Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
  11. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
  12. Received any live vaccine in the 4 weeks prior to screening.
  13. Known active tuberculosis.
  14. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
  15. History of pulmonary alveolar proteinosis (PAP).
  16. Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
  17. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
  18. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
  19. Previous participation in an ACTIV-5/Big Effect Trial (BET).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04583969


Locations
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Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Study Protocol  [PDF] February 10, 2022
Statistical Analysis Plan  [PDF] May 23, 2022
Informed Consent Form  [PDF] February 11, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04583969    
Other Study ID Numbers: 20-0013B
First Posted: October 12, 2020    Key Record Dates
Results First Posted: June 5, 2023
Last Update Posted: June 5, 2023
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Adults
COVID-19
Multicenter
Putative
Therapeutics
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
 Lung Diseases
Respiratory Tract Diseases
Remdesivir
Lenzilumab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-Inflammatory Agents