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

A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04988035

Enrollment

201

Registered

2021-08-03

Start date

2021-08-03

Completion date

2022-04-23

Last updated

2023-06-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19

Keywords

Adults, covid-19, Multicenter, Putative, Therapeutics

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

Interventions

DRUGDanicopan

Danicopan is a small molecule, orally administered complement factor D (FD) inhibitor

OTHERPlacebo

Danicopan matching placebo tablet

DRUGRemdesivir

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	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

Measure	Time frame	Description
Time to Sustained Recovery	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 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	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	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)	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.
Change From Baseline in Ferritin	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.
Change From Baseline in D-dimer	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.
Change From Baseline in Fibrinogen	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.
Change From Baseline in Alanine Aminotransferase (ALT)	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.
Change From Baseline in Aspartate Transaminase (AST)	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.
Change From Baseline in Creatinine	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.
Change From Baseline in International Normalized Ratio (INR)	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.
Change From Baseline in Hemoglobin	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.
Change From Baseline in Platelets Count	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.
Change From Baseline in Total Bilirubin	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.
Change From Baseline in White Blood Cell (WBC) Count	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.
Change From Baseline in Neutrophils	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.
Change From Baseline in Eosinophils	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.
Change From Baseline in Basophils	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.
Change From Baseline in Lymphocytes	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.
Change From Baseline in Monocytes	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.
Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)	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.
Number of Participants Reporting Serious Adverse Events (SAEs)	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.
Number of Participants Who Discontinued or Temporarily Suspended Study Treatment	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.
Duration of Hospitalization	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.
Duration of Intensive Care Unit (ICU) Stay	Day 1 through Day 29	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	Day 1 through Day 29	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	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.
Days of New Non-invasive Ventilation/High Flow Oxygen Use	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.
Days of Non-invasive Ventilation/High Flow Oxygen Use	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.
Days of Supplemental Oxygen Use	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.
Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use	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.
Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use	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.
Mean Change in Ordinal Scale	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.
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29	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	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.
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29	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. Results are reported as Kaplan Meier estimates.
59-day Participant Mortality	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.
Time to an Improvement of One Category From Baseline Using an Ordinal Scale	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.
Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale	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
Time to Death	Day 1 through Day 29	The time death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.
28-day Participant Mortality	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.

Countries

United States

Participant flow

Recruitment details

Participants were male and non-pregnant female adults who were 18 years of age or older and hospitalized with COVID-19. Participants were enrolled between 03AUG2021 and 21FEB2022.

Participants by arm

Arm	Count
Remdesivir + Danicopan 200 mg 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 PO (300 mg for \>=70 years) PO loading dose danicopan, followed by 250 mg (200mg \>=70 years) 4 times daily while hospitalized up to a 14-day total course. End of danicopan treatment tapered as 250 mg (or 200mg for \>=70 years) 3 times daily for 2 days, followed by 250 mg (or 200mg for \>=70 years) twice daily for 2 days, until complete cessation.	98
Remdesivir + Placebo 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 PO (300 mg for \>=70 years) loading dose danicopan matching placebo, followed by 250 mg (200mg \>=70 years) 4 times daily while hospitalized up to a 14-day total course. End of danicopan matching placebo treatment tapered as 250 mg (or 200mg for \>=70 years) 3 times daily for 2 days, followed by 250 mg (or 200mg for \>=70 years) twice daily for 2 days, until complete cessation.	103
Total	201

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	19	13
Overall Study	Lost to Follow-up	12	6
Overall Study	Other include randomized but not dosed and participant condition change (improvement)	2	2
Overall Study	Protocol Violation	0	1
Overall Study	Withdrawal by Subject	2	4

Baseline characteristics

Characteristic	Remdesivir + Placebo	Remdesivir + Danicopan	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	29 Participants	25 Participants	54 Participants
Age, Categorical Between 18 and 65 years	74 Participants	73 Participants	147 Participants
Age, Continuous	55.7 years STANDARD_DEVIATION 14.6	55.9 years STANDARD_DEVIATION 14.6	55.8 years STANDARD_DEVIATION 14.5
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants	18 Participants	37 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants	80 Participants	164 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	14 Participants	14 Participants	28 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	5 Participants	7 Participants
Race (NIH/OMB) White	87 Participants	77 Participants	164 Participants
Region of Enrollment United States	103 participants	98 participants	201 participants
Sex: Female, Male Female	40 Participants	40 Participants	80 Participants
Sex: Female, Male Male	63 Participants	58 Participants	121 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	19 / 98	14 / 103
other Total, other adverse events	8 / 96	17 / 99
serious Total, serious adverse events	31 / 96	23 / 99

Outcome results

Primary

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

Time frame: Day 8

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	2. Not. hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	24 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	6. Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices	18 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	5 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	7. Hospitalized, on invasive mechanical ventilation or ECMO	9 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	3. Hospitalized,not req new or increased supplemental O2 - no longer req ongoing medical care	1 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	8. Death	5 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	5. Hospitalized, requiring new or increased supplemental O2	21 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	Missing	2 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	1 . Not hospitalized, no new or increased limitations on activities	11 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	Missing	3 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	1 . Not hospitalized, no new or increased limitations on activities	15 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	2. Not. hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	28 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	3. Hospitalized,not req new or increased supplemental O2 - no longer req ongoing medical care	3 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	3 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	5. Hospitalized, requiring new or increased supplemental O2	21 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	6. Hospitalized, requiring new or increased non-invasive ventilation or high-flow oxygen devices	19 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	7. Hospitalized, on invasive mechanical ventilation or ECMO	6 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	8. Death	1 Participants

Comparison: Includes all ordinal score categories. Odds ratio of a better clinical status score, confidence interval and p-value estimated from a proportional odds model adjusted for baseline steroid use and baseline ordinal score. Missing data imputed using multiple imputation (MI) for participants lost to follow-up before Day 8 while hospitalized, in hospice, long term acute care, or transferred to other hospital while those participants lost to follow-up after discharge to home are assigned a score of 2.p-value: 0.0995% CI: [0.38, 1.07]Proportional odds model

Secondary

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.

Time frame: Day 1 through Day 15

Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, classified by their actual treatment assignment.

Arm	Measure	Value (NUMBER)
Remdesivir + Danicopan	14-day Participant Mortality	0.14 Proportion of participants
Remdesivir + Placebo	14-day Participant Mortality	0.08 Proportion of participants

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (NUMBER)
Remdesivir + Danicopan	28-day Participant Mortality	0.18 Proportion of participants
Remdesivir + Placebo	28-day Participant Mortality	0.13 Proportion of participants

Secondary

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 frame: Day 1 through Day 60

Arm	Measure	Value (NUMBER)
Remdesivir + Danicopan	59-day Participant Mortality	0.21 Proportion of participants
Remdesivir + Placebo	59-day Participant Mortality	0.14 Proportion of participants

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies with available data at baseline and post baseline assessment time point, analyzed as treated.

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 3	1.2 U/L	Standard Deviation 17.2
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 5	23.7 U/L	Standard Deviation 162
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 8	-9.6 U/L	Standard Deviation 38.7
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 11	20.4 U/L	Standard Deviation 139.2
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 15	18.3 U/L	Standard Deviation 121
Remdesivir + Danicopan	Change From Baseline in Alanine Aminotransferase (ALT)	Day 29	3.7 U/L	Standard Deviation 116.1
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 15	-3.2 U/L	Standard Deviation 40.1
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 3	3.9 U/L	Standard Deviation 26.2
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 11	-1.0 U/L	Standard Deviation 61.8
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 5	11.4 U/L	Standard Deviation 39.8
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 29	-7.9 U/L	Standard Deviation 25.9
Remdesivir + Placebo	Change From Baseline in Alanine Aminotransferase (ALT)	Day 8	-0.5 U/L	Standard Deviation 36.8

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 3	-9.0 U/L	Standard Deviation 22.5
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 5	-1.2 U/L	Standard Deviation 127.2
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 8	-22.3 U/L	Standard Deviation 33.5
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 11	4.4 U/L	Standard Deviation 127.5
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 15	-2.5 U/L	Standard Deviation 85.8
Remdesivir + Danicopan	Change From Baseline in Aspartate Transaminase (AST)	Day 29	-12.3 U/L	Standard Deviation 72.4
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 15	-18.1 U/L	Standard Deviation 24.3
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 3	-5.8 U/L	Standard Deviation 29.3
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 11	-16.6 U/L	Standard Deviation 37.4
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 5	-8.2 U/L	Standard Deviation 25.5
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 29	-12.7 U/L	Standard Deviation 15.6
Remdesivir + Placebo	Change From Baseline in Aspartate Transaminase (AST)	Day 8	-16.7 U/L	Standard Deviation 21.5

Secondary

Change From Baseline in Basophils

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 3	0.0000 10^9 cells/L	Standard Deviation 0.0533
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 5	0.0027 10^9 cells/L	Standard Deviation 0.0627
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 8	0.0100 10^9 cells/L	Standard Deviation 0.0651
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 11	0.0081 10^9 cells/L	Standard Deviation 0.1017
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 15	0.0326 10^9 cells/L	Standard Deviation 0.0419
Remdesivir + Danicopan	Change From Baseline in Basophils	Day 29	0.0578 10^9 cells/L	Standard Deviation 0.0857
Remdesivir + Placebo	Change From Baseline in Basophils	Day 15	0.0191 10^9 cells/L	Standard Deviation 0.0532
Remdesivir + Placebo	Change From Baseline in Basophils	Day 3	0.0111 10^9 cells/L	Standard Deviation 0.0502
Remdesivir + Placebo	Change From Baseline in Basophils	Day 11	0.0260 10^9 cells/L	Standard Deviation 0.0689
Remdesivir + Placebo	Change From Baseline in Basophils	Day 5	0.0119 10^9 cells/L	Standard Deviation 0.0363
Remdesivir + Placebo	Change From Baseline in Basophils	Day 29	0.0264 10^9 cells/L	Standard Deviation 0.0387
Remdesivir + Placebo	Change From Baseline in Basophils	Day 8	0.0340 10^9 cells/L	Standard Deviation 0.1233

Secondary

Change From Baseline in C-Reactive Protein (CRP)

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 5	-47.823 mg/L	Standard Deviation 70.138
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 11	-13.505 mg/L	Standard Deviation 104.003
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 3	-21.477 mg/L	Standard Deviation 131.757
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 15	19.767 mg/L	Standard Deviation 296.305
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 8	-33.995 mg/L	Standard Deviation 78.869
Remdesivir + Danicopan	Change From Baseline in C-Reactive Protein (CRP)	Day 29	-48.736 mg/L	Standard Deviation 94.286
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 8	-73.535 mg/L	Standard Deviation 209.962
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 3	-48.165 mg/L	Standard Deviation 161.358
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 5	-46.581 mg/L	Standard Deviation 229.326
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 29	-48.342 mg/L	Standard Deviation 52.545
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 11	-47.521 mg/L	Standard Deviation 94.728
Remdesivir + Placebo	Change From Baseline in C-Reactive Protein (CRP)	Day 15	-33.077 mg/L	Standard Deviation 104.98

Secondary

Change From Baseline in Creatinine

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 3	-0.006 mg/dL	Standard Deviation 0.218
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 5	0.045 mg/dL	Standard Deviation 0.413
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 8	0.030 mg/dL	Standard Deviation 0.298
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 11	0.133 mg/dL	Standard Deviation 0.514
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 15	0.139 mg/dL	Standard Deviation 0.537
Remdesivir + Danicopan	Change From Baseline in Creatinine	Day 29	5.911 mg/dL	Standard Deviation 29.708
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 15	-0.029 mg/dL	Standard Deviation 0.385
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 3	-0.035 mg/dL	Standard Deviation 0.324
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 11	0.023 mg/dL	Standard Deviation 0.762
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 5	-0.031 mg/dL	Standard Deviation 0.424
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 29	-0.088 mg/dL	Standard Deviation 0.252
Remdesivir + Placebo	Change From Baseline in Creatinine	Day 8	0.428 mg/dL	Standard Deviation 2.996

Secondary

Change From Baseline in D-dimer

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 3	194.0 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 3158.5
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 5	233.3 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 4125.5
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 8	715.3 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 8375.4
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 11	-920.2 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 7419.1
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 15	-1698.7 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 6146.3
Remdesivir + Danicopan	Change From Baseline in D-dimer	Day 29	-1609.5 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 5503.6
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 15	-163.2 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 2133.1
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 3	-318.2 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 5816
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 11	1358.9 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 6896.4
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 5	1006.2 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 18885.5
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 29	-669.0 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 2961.1
Remdesivir + Placebo	Change From Baseline in D-dimer	Day 8	-2594.2 µg/L fibrinogen equivalent units (FEU)	Standard Deviation 17770.5

Secondary

Change From Baseline in Eosinophils

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 3	-0.0055 10^9 cells/L	Standard Deviation 0.0912
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 5	0.0073 10^9 cells/L	Standard Deviation 0.0978
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 8	0.0750 10^9 cells/L	Standard Deviation 0.1802
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 11	0.1230 10^9 cells/L	Standard Deviation 0.223
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 15	0.1548 10^9 cells/L	Standard Deviation 0.1638
Remdesivir + Danicopan	Change From Baseline in Eosinophils	Day 29	0.2211 10^9 cells/L	Standard Deviation 0.1874
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 15	0.1112 10^9 cells/L	Standard Deviation 0.1207
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 3	0.0047 10^9 cells/L	Standard Deviation 0.0769
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 11	0.0589 10^9 cells/L	Standard Deviation 0.1085
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 5	0.0559 10^9 cells/L	Standard Deviation 0.1957
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 29	0.1812 10^9 cells/L	Standard Deviation 0.1525
Remdesivir + Placebo	Change From Baseline in Eosinophils	Day 8	0.0569 10^9 cells/L	Standard Deviation 0.1788

Secondary

Change From Baseline in Ferritin

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 3	-54.975 µg/L	Standard Deviation 606.748
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 5	229.343 µg/L	Standard Deviation 3806.52
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 8	-399.190 µg/L	Standard Deviation 590.849
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 11	-256.244 µg/L	Standard Deviation 949.15
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 15	-400.214 µg/L	Standard Deviation 747.352
Remdesivir + Danicopan	Change From Baseline in Ferritin	Day 29	-556.645 µg/L	Standard Deviation 797.015
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 15	-419.459 µg/L	Standard Deviation 666.368
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 3	-154.437 µg/L	Standard Deviation 524.763
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 11	-505.825 µg/L	Standard Deviation 705.538
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 5	-364.747 µg/L	Standard Deviation 571.17
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 29	-534.470 µg/L	Standard Deviation 603.121
Remdesivir + Placebo	Change From Baseline in Ferritin	Day 8	-400.668 µg/L	Standard Deviation 710.409

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 3	-96.062 mg/dL	Standard Deviation 87.116
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 5	-121.644 mg/dL	Standard Deviation 128.43
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 8	-100.419 mg/dL	Standard Deviation 192.326
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 11	-90.535 mg/dL	Standard Deviation 218.352
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 15	10.394 mg/dL	Standard Deviation 238.314
Remdesivir + Danicopan	Change From Baseline in Fibrinogen	Day 29	-4.909 mg/dL	Standard Deviation 232.659
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 15	1.647 mg/dL	Standard Deviation 255.244
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 3	-67.054 mg/dL	Standard Deviation 122.421
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 11	38.375 mg/dL	Standard Deviation 269.113
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 5	-99.074 mg/dL	Standard Deviation 183.816
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 29	-65.423 mg/dL	Standard Deviation 200.488
Remdesivir + Placebo	Change From Baseline in Fibrinogen	Day 8	-59.927 mg/dL	Standard Deviation 264.074

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 3	-0.26 g/dL	Standard Deviation 0.84
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 5	-0.05 g/dL	Standard Deviation 1.2
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 8	-0.45 g/dL	Standard Deviation 1.24
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 11	-1.01 g/dL	Standard Deviation 1.56
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 15	-1.10 g/dL	Standard Deviation 1.65
Remdesivir + Danicopan	Change From Baseline in Hemoglobin	Day 29	-1.17 g/dL	Standard Deviation 1.51
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 15	-0.83 g/dL	Standard Deviation 1.92
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 3	-0.16 g/dL	Standard Deviation 0.95
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 11	-0.94 g/dL	Standard Deviation 2.5
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 5	-0.27 g/dL	Standard Deviation 1.18
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 29	-0.58 g/dL	Standard Deviation 2.2
Remdesivir + Placebo	Change From Baseline in Hemoglobin	Day 8	-0.24 g/dL	Standard Deviation 1.41

Secondary

Change From Baseline in International Normalized Ratio (INR)

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 3	-0.064 Ratio	Standard Deviation 0.912
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 5	-0.071 Ratio	Standard Deviation 0.844
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 8	0.012 Ratio	Standard Deviation 0.148
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 11	0.032 Ratio	Standard Deviation 0.194
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 15	-0.023 Ratio	Standard Deviation 0.199
Remdesivir + Danicopan	Change From Baseline in International Normalized Ratio (INR)	Day 29	-0.024 Ratio	Standard Deviation 0.149
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 15	0.063 Ratio	Standard Deviation 0.532
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 3	-0.005 Ratio	Standard Deviation 0.342
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 11	-0.047 Ratio	Standard Deviation 0.41
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 5	-0.037 Ratio	Standard Deviation 0.679
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 29	-0.066 Ratio	Standard Deviation 0.135
Remdesivir + Placebo	Change From Baseline in International Normalized Ratio (INR)	Day 8	-0.129 Ratio	Standard Deviation 0.625

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 3	0.2654 10^9 cells/L	Standard Deviation 1.0297
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 5	0.4474 10^9 cells/L	Standard Deviation 1.236
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 8	0.5374 10^9 cells/L	Standard Deviation 1.7658
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 11	0.3217 10^9 cells/L	Standard Deviation 2.5357
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 15	0.5042 10^9 cells/L	Standard Deviation 1.4566
Remdesivir + Danicopan	Change From Baseline in Lymphocytes	Day 29	2.0835 10^9 cells/L	Standard Deviation 6.8237
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 15	0.1346 10^9 cells/L	Standard Deviation 2.8093
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 3	0.1144 10^9 cells/L	Standard Deviation 1.9437
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 11	0.6910 10^9 cells/L	Standard Deviation 1.4222
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 5	0.3570 10^9 cells/L	Standard Deviation 0.5793
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 29	0.0827 10^9 cells/L	Standard Deviation 3.2091
Remdesivir + Placebo	Change From Baseline in Lymphocytes	Day 8	0.0605 10^9 cells/L	Standard Deviation 2.2513

Secondary

Change From Baseline in Monocytes

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 3	0.1490 10^9 cells/L	Standard Deviation 0.3267
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 5	0.2622 10^9 cells/L	Standard Deviation 0.3589
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 8	0.4576 10^9 cells/L	Standard Deviation 0.6573
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 11	0.6989 10^9 cells/L	Standard Deviation 1.5589
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 15	0.2775 10^9 cells/L	Standard Deviation 0.3628
Remdesivir + Danicopan	Change From Baseline in Monocytes	Day 29	0.3728 10^9 cells/L	Standard Deviation 0.3899
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 15	0.2062 10^9 cells/L	Standard Deviation 1.2706
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 3	0.1991 10^9 cells/L	Standard Deviation 1.0844
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 11	0.1333 10^9 cells/L	Standard Deviation 0.3751
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 5	0.1637 10^9 cells/L	Standard Deviation 0.3833
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 29	-0.0564 10^9 cells/L	Standard Deviation 0.826
Remdesivir + Placebo	Change From Baseline in Monocytes	Day 8	0.3227 10^9 cells/L	Standard Deviation 1.6344

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEDIAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 3	0.2636 10^9 cells/L	Standard Deviation 3.4635
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 5	3.7855 10^9 cells/L	Standard Deviation 15.4339
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 8	4.2105 10^9 cells/L	Standard Deviation 5.2679
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 11	3.0045 10^9 cells/L	Standard Deviation 6.6829
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 15	0.3248 10^9 cells/L	Standard Deviation 5.0057
Remdesivir + Danicopan	Change From Baseline in Neutrophils	Day 29	-1.8560 10^9 cells/L	Standard Deviation 5.1346
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 15	-2.7688 10^9 cells/L	Standard Deviation 13.1915
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 3	-0.2675 10^9 cells/L	Standard Deviation 9.018
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 11	1.6819 10^9 cells/L	Standard Deviation 4.3946
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 5	1.5898 10^9 cells/L	Standard Deviation 3.5187
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 29	-3.8238 10^9 cells/L	Standard Deviation 14.5807
Remdesivir + Placebo	Change From Baseline in Neutrophils	Day 8	0.1951 10^9 cells/L	Standard Deviation 12.9127

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 3	35.83 10^9 cells/L	Standard Deviation 59.09
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 5	65.06 10^9 cells/L	Standard Deviation 94.9
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 8	69.88 10^9 cells/L	Standard Deviation 128.91
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 11	19.90 10^9 cells/L	Standard Deviation 140.27
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 15	-9.04 10^9 cells/L	Standard Deviation 120.68
Remdesivir + Danicopan	Change From Baseline in Platelets Count	Day 29	89.44 10^9 cells/L	Standard Deviation 129.66
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 15	10.45 10^9 cells/L	Standard Deviation 119.24
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 3	53.84 10^9 cells/L	Standard Deviation 51.95
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 11	89.37 10^9 cells/L	Standard Deviation 122.81
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 5	87.31 10^9 cells/L	Standard Deviation 81.39
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 29	34.34 10^9 cells/L	Standard Deviation 85.11
Remdesivir + Placebo	Change From Baseline in Platelets Count	Day 8	120.49 10^9 cells/L	Standard Deviation 125.52

Secondary

Change From Baseline in Total Bilirubin

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 3	-0.425 mg/dL	Standard Deviation 3.845
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 5	-0.494 mg/dL	Standard Deviation 4.334
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 8	-0.715 mg/dL	Standard Deviation 5.193
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 11	0.075 mg/dL	Standard Deviation 0.274
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 15	0.076 mg/dL	Standard Deviation 0.332
Remdesivir + Danicopan	Change From Baseline in Total Bilirubin	Day 29	-0.012 mg/dL	Standard Deviation 0.313
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 15	0.088 mg/dL	Standard Deviation 0.352
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 3	0.009 mg/dL	Standard Deviation 0.216
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 11	0.088 mg/dL	Standard Deviation 0.314
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 5	0.040 mg/dL	Standard Deviation 0.311
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 29	0.079 mg/dL	Standard Deviation 0.305
Remdesivir + Placebo	Change From Baseline in Total Bilirubin	Day 8	0.049 mg/dL	Standard Deviation 0.345

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 3	2.041 10^9 cells/L	Standard Deviation 9.684
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 5	3.276 10^9 cells/L	Standard Deviation 4.577
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 8	5.625 10^9 cells/L	Standard Deviation 5.73
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 11	5.370 10^9 cells/L	Standard Deviation 7.611
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 15	1.491 10^9 cells/L	Standard Deviation 5.035
Remdesivir + Danicopan	Change From Baseline in White Blood Cell (WBC) Count	Day 29	0.396 10^9 cells/L	Standard Deviation 5.066
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 15	0.710 10^9 cells/L	Standard Deviation 4.484
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 3	1.247 10^9 cells/L	Standard Deviation 2.684
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 11	4.050 10^9 cells/L	Standard Deviation 5.933
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 5	2.550 10^9 cells/L	Standard Deviation 3.805
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 29	-0.333 10^9 cells/L	Standard Deviation 4.071
Remdesivir + Placebo	Change From Baseline in White Blood Cell (WBC) Count	Day 8	3.483 10^9 cells/L	Standard Deviation 5.101

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use	0.0 days
Remdesivir + Placebo	Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use	0.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants not on invasive ventilation/ECMO at baseline were included in the analysis.

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use	0.0 days
Remdesivir + Placebo	Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use	0.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants in the 'hospitalized requiring new or increased supplemental oxygen ordinal scale' or better at baseline were included in the analysis.

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Days of New Non-invasive Ventilation/High Flow Oxygen Use	0.0 days
Remdesivir + Placebo	Days of New Non-invasive Ventilation/High Flow Oxygen Use	0.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Days of Non-invasive Ventilation/High Flow Oxygen Use	3.0 days
Remdesivir + Placebo	Days of Non-invasive Ventilation/High Flow Oxygen Use	3.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Days of Supplemental Oxygen Use	19.5 days
Remdesivir + Placebo	Days of Supplemental Oxygen Use	23.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Group	Value (MEDIAN)
Remdesivir + Danicopan	Duration of Hospitalization	Hospitalized for Any Reason	10.0 days
Remdesivir + Danicopan	Duration of Hospitalization	Hospitalized for COVID-19	9.5 days
Remdesivir + Placebo	Duration of Hospitalization	Hospitalized for Any Reason	8.0 days
Remdesivir + Placebo	Duration of Hospitalization	Hospitalized for COVID-19	8.0 days

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Duration of Intensive Care Unit (ICU) Stay	0.0 days
Remdesivir + Placebo	Duration of Intensive Care Unit (ICU) Stay	0.0 days

Secondary

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.

Time frame: Days 1, 3, 5, 8, 11, 15, 22, 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 15	-2.0 units on a scale	Standard Deviation 2.4
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 22	-2.3 units on a scale	Standard Deviation 2.5
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 3	0.0 units on a scale	Standard Deviation 0.4
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 5	-0.3 units on a scale	Standard Deviation 1.1
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 8	-1.2 units on a scale	Standard Deviation 1.9
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 11	-1.6 units on a scale	Standard Deviation 2
Remdesivir + Danicopan	Mean Change in Ordinal Scale	Day 29	-2.3 units on a scale	Standard Deviation 2.6
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 22	-2.6 units on a scale	Standard Deviation 2.3
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 15	-2.5 units on a scale	Standard Deviation 2.1
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 8	-1.7 units on a scale	Standard Deviation 1.8
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 29	-2.7 units on a scale	Standard Deviation 2.3
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 3	0.0 units on a scale	Standard Deviation 0.5
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 11	-2.1 units on a scale	Standard Deviation 1.9
Remdesivir + Placebo	Mean Change in Ordinal Scale	Day 5	-0.5 units on a scale	Standard Deviation 1.1

Secondary

Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15

Time frame: Day 15

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	1. Not hospitalized, no new or increased limitations on activities	22 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	5. Hospitalized, requiring new or increased supplemental O2	13 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care	0 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	6. Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices	4 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	2. Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	37 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	7. Hospitalized, on invasive mechanical ventilation or ECMO	7 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	8. Death	12 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	1 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	8. Death	6 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	1. Not hospitalized, no new or increased limitations on activities	27 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	2. Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	42 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care	1 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	1 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	5. Hospitalized, requiring new or increased supplemental O2	10 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	6. Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices	5 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	7. Hospitalized, on invasive mechanical ventilation or ECMO	7 Participants

Comparison: Includes all ordinal score categories. OR of a better clinical status score, confidence interval, and p-value estimated from a proportional odds model adjusted for baseline steroid use and baseline ordinal score. Missing data imputed using last observation carried forward for participants lost to follow-up before Day 15 while hospitalized, in hospice, long term acute care, or transferred to other hospital. Participants lost to follow-up before Day 15 after discharge are given a score of 2.p-value: 0.17795% CI: [0.42, 1.17]Proportional odds model

Secondary

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

Time frame: Day 29

Arm	Measure	Category	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	1. Not hospitalized, no new or increased limitations on activities	33 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	2. Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	34 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care	0 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	1 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	5. Hospitalized, requiring new or increased supplemental O2	6 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	6. Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices	1 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	7. Hospitalized, on invasive mechanical ventilation or ECMO	4 Participants
Remdesivir + Danicopan	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	8. Death	17 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	8. Death	12 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	1. Not hospitalized, no new or increased limitations on activities	35 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	5. Hospitalized, requiring new or increased supplemental O2	7 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	2. Not hosp., but new or incr. limit on activities and/or req. new or incr. home O2, CPAP, or BiPAP	42 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	7. Hospitalized, on invasive mechanical ventilation or ECMO	3 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	3. Hospitalized, not req new or increased supplemental O2 - no longer req ongoing medical care	0 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	6. Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices	0 Participants
Remdesivir + Placebo	Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	4. Hospitalized, not req new or increased supplemental O2 - req ongoing medical care	0 Participants

Comparison: Includes all ordinal score categories. OR of a better clinical status score, confidence interval, and p-value estimated from a proportional odds model adjusted for baseline steroid use and baseline ordinal score. Missing data imputed using last observation carried forward for participants lost to follow-up before Day 29 while hospitalized, in hospice, long term acute care, or transferred to other hospital. Participants lost to follow-up before Day 29 after discharge are given a score of 2.p-value: 0.42795% CI: [0.48, 1.36]Proportional odds model

Secondary

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.

Time frame: Day 1 through Day 60

Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)	43 Participants
Remdesivir + Placebo	Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)	46 Participants

Secondary

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.

Time frame: Day 1 through Day 60

Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Reporting Serious Adverse Events (SAEs)	31 Participants
Remdesivir + Placebo	Number of Participants Reporting Serious Adverse Events (SAEs)	23 Participants

Secondary

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.

Time frame: Day 1 through Day 29

Population: The safety population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as treated.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants Who Discontinued or Temporarily Suspended Study Treatment	9 Participants
Remdesivir + Placebo	Number of Participants Who Discontinued or Temporarily Suspended Study Treatment	8 Participants

Secondary

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.

Time frame: Day 1 through Day 29

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use	16 Participants
Remdesivir + Placebo	Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use	14 Participants

Secondary

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.

Time frame: Day 1 through Day 29

Population: The modified intention-to-treat (mITT) population includes all randomized participants who received at least one dose of investigational product other than standard of care therapies, analyzed as randomized. Only participants in the 'hospitalized requiring new or increased supplemental oxygen ordinal scale' or better at baseline were included in the analysis.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Remdesivir + Danicopan	Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use	14 Participants
Remdesivir + Placebo	Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use	18 Participants

Secondary

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.

Time frame: Day 29

Arm	Measure	Value (NUMBER)
Remdesivir + Danicopan	Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29	0.78 Proportion of participants
Remdesivir + Placebo	Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29	0.85 Proportion of participants

Secondary

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 frame: Day 1 through Day 29

Arm	Measure	Value (NUMBER)
Remdesivir + Danicopan	Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29	0.79 Proportion of participants
Remdesivir + Placebo	Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29	0.83 Proportion of participants

Comparison: Odds ratio, confidence interval, and p-value estimated from a logistic regression model adjusted for baseline dexamethasone use, baseline ordinal score, age, and baseline C-Reactive Protein (CRP).p-value: 0.35895% CI: [0.31, 1.53]Regression, Logistic

Secondary

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 frame: Day 1 through Day 60

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Time to an Improvement of One Category From Baseline Using an Ordinal Scale	8.0 days
Remdesivir + Placebo	Time to an Improvement of One Category From Baseline Using an Ordinal Scale	6.0 days

p-value: 0.10995% CI: [0.56, 1.06]Regression, Cox

Secondary

Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale

Time frame: Day 1 through Day 60

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale	13.0 days
Remdesivir + Placebo	Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale	10.0 days

p-value: 0.03695% CI: [0.51, 0.98]Regression, Cox

Secondary

Time to Death

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

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Time to Death	NA days
Remdesivir + Placebo	Time to Death	NA days

Secondary

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.

Time frame: Day 1 through Day 60

Arm	Measure	Value (MEDIAN)
Remdesivir + Danicopan	Time to Sustained Recovery	13.0 days
Remdesivir + Placebo	Time to Sustained Recovery	7.0 days

Comparison: Hazard ratio, confidence interval, and p-value estimated from a Cox model adjusted for baseline steroid use and baseline ordinal score.p-value: 0.01495% CI: [0.46, 0.92]Regression, Cox

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

14-day Participant Mortality

28-day Participant Mortality

59-day Participant Mortality

Change From Baseline in Alanine Aminotransferase (ALT)

Change From Baseline in Aspartate Transaminase (AST)

Change From Baseline in Basophils

Change From Baseline in C-Reactive Protein (CRP)

Change From Baseline in Creatinine

Change From Baseline in D-dimer

Change From Baseline in Eosinophils

Change From Baseline in Ferritin

Change From Baseline in Fibrinogen

Change From Baseline in Hemoglobin

Change From Baseline in International Normalized Ratio (INR)

Change From Baseline in Lymphocytes

Change From Baseline in Monocytes

Change From Baseline in Neutrophils

Change From Baseline in Platelets Count

Change From Baseline in Total Bilirubin

Change From Baseline in White Blood Cell (WBC) Count

Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use

Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use

Days of New Non-invasive Ventilation/High Flow Oxygen Use

Days of Non-invasive Ventilation/High Flow Oxygen Use

Days of Supplemental Oxygen Use

Duration of Hospitalization

Duration of Intensive Care Unit (ICU) Stay

Mean Change in Ordinal Scale

Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15

Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29

Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)

Number of Participants Reporting Serious Adverse Events (SAEs)

Number of Participants Who Discontinued or Temporarily Suspended Study Treatment

Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use

Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use

Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29

Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29

Time to an Improvement of One Category From Baseline Using an Ordinal Scale

Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale

Time to Death

Time to Sustained Recovery