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

Primary Purpose

COVID-19

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Danicopan
Placebo
Remdesivir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Adults, covid-19, Multicenter, Putative, Therapeutics

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Admitted to a hospital with symptoms suggestive of 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 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 scale category 5, 6, or 7).*

    *If written documentation of the positive test result is not available at the time of enrollment (e.g., report came from other institution), the test should be repeated and the subject may be enrolled if positive.

  7. Women of childbearing potential and men must agree to either abstinence or use at least one acceptable method of contraception** from the time of screening through 30 days after the last dose of danicopan for women and 90 days after the last dose for men.

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

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

    1. Subjects with an eGFR 15-30 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 an eGFR <15 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. Treatment with a complement inhibitor in the prior 8 weeks.*
  8. Has active uncontrolled opportunistic infection, or uncontrolled cirrhosis.*
  9. History of infection with N. meningitidis.*
  10. Known history of hypersensitivity to danicopan or its excipients.*
  11. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
  12. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
  13. History of liver cirrhosis.*
  14. Previous participation in an ACTIV-5/BET trial.
  15. Refuses to refrain from breastfeeding from the time of screening through 30 days after the last dose of danicopan.*
  16. Refuses to receive prophylactic antibiotics against meningococcal infections if the subject has not been vaccinated in the 3 years prior to Study Day 1.

Sites / Locations

  • University of Alabama at Birmingham School of Medicine - Infectious Disease
  • Kern Medical Center
  • UCSF Fresno Center for Medical Education and Research - Clinical Research Center
  • University of California Los Angeles Medical Center - Westwood Clinic
  • Hoag Hospital Newport Beach
  • Penrose Hospital - Emergency Medicine
  • St. Francis Medical Center
  • St. Anthony Hospital
  • St. Anthony Hospital North Health Campus
  • Nuvance Health Danbury Hospital - Infectious Disease
  • Yale School of Medicine - The Anlyan Center for Medical Research & Education - Immunobiology
  • Nuvance Health - Norwalk Hospital - Asthma Pulmonary and Critical Care Medicine
  • University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
  • Mayo Clinic Florida
  • Great Lakes Clinical Trials
  • Carle Foundation Hospital
  • Northwestern Medicine - Central DuPage Hospital - Infectious Disease
  • Norton Healthcare
  • University of Louisville - Division of Infectious Diseases
  • Brigham and Women's Hospital - Infectious Diseases
  • William Beaumont Hospital - Royal Oak Campus - Infectious Disease
  • Hennepin Healthcare Research Institute
  • Mayo Clinic, Rochester - Infectious Diseases
  • University of Nebraska Medical Center - Infectious Diseases
  • Jacobi Medical Center
  • Montefiore Medical Center - Infectious Diseases
  • The State University of New York - University at Buffalo - Department of Medicine
  • Mount Sinai School of Medicine - Medicine - Infectious Diseases
  • Nuvance Health - Vassar Brothers Medical Center
  • Stony Brook Medicine - Stony Brook University Hospita
  • Wake Forest Baptist Health - Infectious Diseases
  • St. Charles Health System - St. Charles Bend Hospital
  • Doylestown Hospital
  • Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
  • Kent County Memorial Hospital
  • Hendrick Health - Hendrick Medical Center
  • Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
  • University of Utah - Infectious Diseases
  • West Virginia University - Infectious Diseases Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

Remdesivir + Danicopan (< 70 years)

Remdesivir + Danicopan (>/= 70 years)

Remdesivir + Placebo (< 70 years)

Remdesivir + Placebo (>/= 70 years)

Arm Description

For participants < 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 400 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan, followed by 250 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan treatment tapered as 250 mg 3 times daily (TID) for 2 days, followed by 250 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan participants, N=100.

For participants >/= 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 300 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan, followed by 200 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan treatment tapered as 200 mg 3 times daily (TID) for 2 days, followed by 200 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan participants, N=100.

For participants < 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 400 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan matching placebo, followed by 250 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan matching placebo treatment tapered as 250 mg 3 times daily (TID) for 2 days, followed by 250 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan matching placebo participants, N=100.

For participants >/= 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 300 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) of loading dose danicopan matching placebo followed by 200 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan matching placebo treatment tapered as 200 mg 3 times daily (TID) for 2 days, followed by 200 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan matching placebo participants, N=100.

Outcomes

Primary Outcome Measures

Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on 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

Secondary Outcome Measures

Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories 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. Results are reported as Kaplan Meier estimates.
Time to Sustained Recovery
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the ordinal scale (and does not return to a score of 4 or higher 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.
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15
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.
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 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 ventilationor extracorporeal membrane oxygenation (ECMO); 8) Death
Change From Baseline in C-Reactive Protein (CRP)
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.
Change From Baseline in Ferritin
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.
Change From Baseline in D-dimer
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.
Change From Baseline in Fibrinogen
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.
Change From Baseline in Alanine Aminotransferase (ALT)
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.
Change From Baseline in Aspartate Transaminase (AST)
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.
Change From Baseline in Creatinine
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.
Change From Baseline in International Normalized Ratio (INR)
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.
Change From Baseline in Hemoglobin
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.
Change From Baseline in Platelets Count
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.
Change From Baseline in Total Bilirubin
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.
Change From Baseline in White Blood Cell (WBC) Count
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.
Change From Baseline in Neutrophils
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.
Change From Baseline in Eosinophils
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.
Change From Baseline in Basophils
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.
Change From Baseline in Lymphocytes
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.
Change From Baseline in Monocytes
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.
Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)
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.
Number of Participants Reporting Serious Adverse Events (SAEs)
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.
Number of Participants Who Discontinued or Temporarily Suspended Study Treatment
Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.
Duration of Hospitalization
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.
Duration of Intensive Care Unit (ICU) Stay
Duration of ICU is defined first as the total number of days spent in an intensive care unit.
Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use
Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.
Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use
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.
Days of New Non-invasive Ventilation/High Flow Oxygen Use
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.
Days of Non-invasive Ventilation/High Flow Oxygen Use
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.
Days of Supplemental Oxygen Use
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.
Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use
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.
Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use
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.
Mean Change in Ordinal Scale
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.
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at 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.
14-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
28-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
59-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.
Time to an Improvement of One Category From Baseline Using an Ordinal Scale
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.
Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale
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
Time to Death
The time death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.

Full Information

First Posted
July 29, 2021
Last Updated
June 6, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT04988035
Brief Title
ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19
Official Title
A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 3, 2021 (Actual)
Primary Completion Date
April 23, 2022 (Actual)
Study Completion Date
April 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

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

5. Study Description

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 COVID-19. 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-C stage will evaluate the combination of remdesivir with danicopan vs remdesivir with a 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, plasma and RNA) research samples on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. 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 danicopan relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.
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 COVID-19. 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-C stage will evaluate the combination of remdesivir with danicopan vs remdesivir with a 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, plasma and RNA) research samples on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. 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 danicopan 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 1) to evaluate the clinical efficacy of danicopan as assessed by time to recovery compared to the control arm 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Adults, covid-19, Multicenter, Putative, Therapeutics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
201 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Remdesivir + Danicopan (< 70 years)
Arm Type
Experimental
Arm Description
For participants < 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 400 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan, followed by 250 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan treatment tapered as 250 mg 3 times daily (TID) for 2 days, followed by 250 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan participants, N=100.
Arm Title
Remdesivir + Danicopan (>/= 70 years)
Arm Type
Experimental
Arm Description
For participants >/= 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 300 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan, followed by 200 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan treatment tapered as 200 mg 3 times daily (TID) for 2 days, followed by 200 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan participants, N=100.
Arm Title
Remdesivir + Placebo (< 70 years)
Arm Type
Active Comparator
Arm Description
For participants < 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized, and 400 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) loading dose danicopan matching placebo, followed by 250 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan matching placebo treatment tapered as 250 mg 3 times daily (TID) for 2 days, followed by 250 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan matching placebo participants, N=100.
Arm Title
Remdesivir + Placebo (>/= 70 years)
Arm Type
Active Comparator
Arm Description
For participants >/= 70 years, 200 mg intravenous (IV) loading dose of Remdesivir on Day 1, followed by a 100 mg once-daily IV maintenance dose up to a 10-day total course while hospitalized and 300 mg oral (PO) (or via nasogastric [NG] or gastrostomy [G] tube) of loading dose danicopan matching placebo followed by 200 mg 4 times daily (QID) for the duration of the hospitalization up to a 14-day total course. End of danicopan matching placebo treatment tapered as 200 mg 3 times daily (TID) for 2 days, followed by 200 mg twice daily (BID) for 2 days, until complete cessation (total treatment duration up to 18 days or 4 days after discharge). Total danicopan matching placebo participants, N=100.
Intervention Type
Drug
Intervention Name(s)
Danicopan
Intervention Description
Danicopan is a small molecule, orally administered complement factor D (FD) inhibitor
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Danicopan matching placebo tablet
Intervention Type
Drug
Intervention Name(s)
Remdesivir
Intervention Description
Remdesivir is a single diastereomer monophosphoramidate prodrug for the intracellular delivery of a modified adenine nucleoside analog GS-441524.
Primary Outcome Measure Information:
Title
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8
Description
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
Time Frame
Day 8
Secondary Outcome Measure Information:
Title
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29
Description
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. Results are reported as Kaplan Meier estimates.
Time Frame
Day 1 through Day 29
Title
Time to Sustained Recovery
Description
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the ordinal scale (and does not return to a score of 4 or higher 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.
Time Frame
Day 1 through Day 60
Title
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15
Description
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.
Time Frame
Day 15
Title
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29
Description
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 ventilationor extracorporeal membrane oxygenation (ECMO); 8) Death
Time Frame
Day 29
Title
Change From Baseline in C-Reactive Protein (CRP)
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Ferritin
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in D-dimer
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Fibrinogen
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Alanine Aminotransferase (ALT)
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Aspartate Transaminase (AST)
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Creatinine
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in International Normalized Ratio (INR)
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Hemoglobin
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Platelets Count
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Total Bilirubin
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in White Blood Cell (WBC) Count
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Neutrophils
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Eosinophils
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Basophils
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Lymphocytes
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Change From Baseline in Monocytes
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Title
Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)
Description
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.
Time Frame
Day 1 through Day 60
Title
Number of Participants Reporting Serious Adverse Events (SAEs)
Description
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.
Time Frame
Day 1 through Day 60
Title
Number of Participants Who Discontinued or Temporarily Suspended Study Treatment
Description
Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.
Time Frame
Day 1 through Day 29
Title
Duration of Hospitalization
Description
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.
Time Frame
Day 1 through Day 29
Title
Duration of Intensive Care Unit (ICU) Stay
Description
Duration of ICU is defined first as the total number of days spent in an intensive care unit.
Time Frame
Day 1 through Day 29
Title
Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use
Description
Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.
Time Frame
Day 1 through Day 29
Title
Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Days of New Non-invasive Ventilation/High Flow Oxygen Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Days of Non-invasive Ventilation/High Flow Oxygen Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Days of Supplemental Oxygen Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use
Description
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.
Time Frame
Day 1 through Day 29
Title
Mean Change in Ordinal Scale
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15, 22, 29
Title
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29
Description
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.
Time Frame
Day 29
Title
14-day Participant Mortality
Description
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
Time Frame
Day 1 through Day 15
Title
28-day Participant Mortality
Description
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
Time Frame
Day 1 through Day 29
Title
59-day Participant Mortality
Description
The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.
Time Frame
Day 1 through Day 60
Title
Time to an Improvement of One Category From Baseline Using an Ordinal Scale
Description
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.
Time Frame
Day 1 through Day 60
Title
Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale
Description
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
Time Frame
Day 1 through Day 60
Title
Time to Death
Description
The time death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.
Time Frame
Day 1 through Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Admitted to a hospital with symptoms suggestive of COVID-19 and requires ongoing medical care. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures. Male or non-pregnant female adult >/=18 years of age at time of enrollment. Illness of any duration and has laboratory-confirmed 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. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or extracorporeal membrane oxygenation (ECMO) (ordinal scale category 5, 6, or 7).* *If written documentation of the positive test result is not available at the time of enrollment (e.g., report came from other institution), the test should be repeated and the subject may be enrolled if positive. Women of childbearing potential and men must agree to either abstinence or use at least one acceptable method of contraception** from the time of screening through 30 days after the last dose of danicopan for women and 90 days after the last dose for men. **Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. 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: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal. Subjects with a low glomerular filtration rate (eGFR), specifically: Subjects with an eGFR 15-30 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. All subjects with an eGFR <15 mL/min (including hemodialysis and hemofiltration) are excluded. Pregnancy or breast feeding Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment. Allergy to any study medication. Received five or more doses of remdesivir prior to screening. Treatment with a complement inhibitor in the prior 8 weeks.* Has active uncontrolled opportunistic infection, or uncontrolled cirrhosis.* History of infection with N. meningitidis.* Known history of hypersensitivity to danicopan or its excipients.* Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results. Positive test for influenza virus during the current illness (influenza testing is not required by protocol). History of liver cirrhosis.* Previous participation in an ACTIV-5/BET trial. Refuses to refrain from breastfeeding from the time of screening through 30 days after the last dose of danicopan.* Refuses to receive prophylactic antibiotics against meningococcal infections if the subject has not been vaccinated in the 3 years prior to Study Day 1.
Facility Information:
Facility Name
University of Alabama at Birmingham School of Medicine - Infectious Disease
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Kern Medical Center
City
Bakersfield
State/Province
California
ZIP/Postal Code
93306-4018
Country
United States
Facility Name
UCSF Fresno Center for Medical Education and Research - Clinical Research Center
City
Fresno
State/Province
California
ZIP/Postal Code
93721
Country
United States
Facility Name
University of California Los Angeles Medical Center - Westwood Clinic
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Hoag Hospital Newport Beach
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Penrose Hospital - Emergency Medicine
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
St. Francis Medical Center
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80923
Country
United States
Facility Name
St. Anthony Hospital
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80228-1704
Country
United States
Facility Name
St. Anthony Hospital North Health Campus
City
Westminster
State/Province
Colorado
ZIP/Postal Code
80023
Country
United States
Facility Name
Nuvance Health Danbury Hospital - Infectious Disease
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
Facility Name
Yale School of Medicine - The Anlyan Center for Medical Research & Education - Immunobiology
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519-1612
Country
United States
Facility Name
Nuvance Health - Norwalk Hospital - Asthma Pulmonary and Critical Care Medicine
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856
Country
United States
Facility Name
University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Great Lakes Clinical Trials
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60640
Country
United States
Facility Name
Carle Foundation Hospital
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Northwestern Medicine - Central DuPage Hospital - Infectious Disease
City
Winfield
State/Province
Illinois
ZIP/Postal Code
60190
Country
United States
Facility Name
Norton Healthcare
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Louisville - Division of Infectious Diseases
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Brigham and Women's Hospital - Infectious Diseases
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115-6110
Country
United States
Facility Name
William Beaumont Hospital - Royal Oak Campus - Infectious Disease
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Hennepin Healthcare Research Institute
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
Mayo Clinic, Rochester - Infectious Diseases
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905-0001
Country
United States
Facility Name
University of Nebraska Medical Center - Infectious Diseases
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68105
Country
United States
Facility Name
Jacobi Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461-1119
Country
United States
Facility Name
Montefiore Medical Center - Infectious Diseases
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2401
Country
United States
Facility Name
The State University of New York - University at Buffalo - Department of Medicine
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Mount Sinai School of Medicine - Medicine - Infectious Diseases
City
New York
State/Province
New York
ZIP/Postal Code
10029-6504
Country
United States
Facility Name
Nuvance Health - Vassar Brothers Medical Center
City
Poughkeepsie
State/Province
New York
ZIP/Postal Code
12601
Country
United States
Facility Name
Stony Brook Medicine - Stony Brook University Hospita
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Wake Forest Baptist Health - Infectious Diseases
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
St. Charles Health System - St. Charles Bend Hospital
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Doylestown Hospital
City
Doylestown
State/Province
Pennsylvania
ZIP/Postal Code
18901
Country
United States
Facility Name
Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Kent County Memorial Hospital
City
Warwick
State/Province
Rhode Island
ZIP/Postal Code
02886
Country
United States
Facility Name
Hendrick Health - Hendrick Medical Center
City
Abilene
State/Province
Texas
ZIP/Postal Code
79601
Country
United States
Facility Name
Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Utah - Infectious Diseases
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
West Virginia University - Infectious Diseases Clinic
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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