Adaptive COVID-19 Treatment Trial 4 (ACTT-4)

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT04640168
• Collaborator: (none)
• Enrollment: 1,010
• Locations: 72
• Arms: 2
• Actual Duration (Months): 6.5
• Patients Per Site: 14
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary research as well as clinical outcome data. However, if infection control or other restrictions limit the ability of the subject to return to the clinic, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Baricitinib; Drug: Dexamethasone; Other: Placebo; Drug: Remdesivir	Phase 3

Detailed Description

This study is an adaptive randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. New arms can be introduced according to scientific and public health needs. There will be interim monitoring to allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. This adaptive platform is used to rapidly evaluate different therapeutics in a population of those hospitalized with moderate to severe COVID-19. The platform will provide a common framework sharing a similar population, design, endpoints, and safety oversight. New stages with new therapeutics can be introduced. One independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make recommendations about early study closure or changes to study arms.

ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary research as well as clinical outcome data. However, if infection control or other restrictions limit the ability of the subject to return to the clinic, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone.

All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized).

The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29. The key secondary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir according to clinical status (8-point ordinal scale) at Day 15.

Contacts:

20-0006 Central Contact

Telephone: [phone]

Email: [e-mail]

Study Design

• Study Type: Interventional
• Actual Enrollment: 1010 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-4)
• Actual Study Start Date: Dec 2, 2020
• Actual Primary Completion Date: May 18, 2021
• Actual Study Completion Date: Jun 18, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Remdesivir plus Baricitinib 200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	Drug: Baricitinib; Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name [1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile. Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.; Other: Placebo; Placebo matching oral baricitinib or intravenous dexamethasone.; Drug: Remdesivir; Drug remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Experimental: Remdesivir plus Dexamethasone 200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	Drug: Dexamethasone; Dexamethasone Sodium Phosphate Injection, USP, is an adrenocortical steroid anti-inflammatory drug. It is a water-soluble inorganic ester of dexamethasone. Each mL contains dexamethasone sodium phosphate equivalent to dexamethasone phosphate 4 mg or dexamethasone 3.33 mg; benzyl alcohol 10 mg added as preservative; sodium citrate dihydrate 11 mg; sodium sulfite 1 mg as an antioxidant.; Other: Placebo; Placebo matching oral baricitinib or intravenous dexamethasone.; Drug: Remdesivir; Drug remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.

Outcome Measures

Primary Outcome Measures

1. The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) [Day 1 through Day 29]

   Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO as of Day 29. Results are reported as Kaplan Meier estimates.

2. The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Race [Day 1 through Day 29]

   Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO as of Day 29. Results are reported as Kaplan Meier estimates.

3. The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Ethnicity [Day 1 through Day 29]

   Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO as of Day 29. Results are reported as Kaplan Meier estimates.

4. The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Sex [Day 1 through Day 29]

   Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO as of Day 29. Results are reported as Kaplan Meier estimates.

Secondary Outcome Measures

1. Change From Baseline in Alanine Aminotransferase (ALT) [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate ALT 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.

2. Change From Baseline in Aspartate Aminotransferase (AST) [Days 1, 3, 5, 8, 11, 15 and 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.

3. Change From Baseline in C-reactive Protein (CRP) [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate CRP 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.

4. Change From Baseline in Creatinine [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate serum creatinine 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.

5. Change From Baseline in D-dimer Concentration [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate d-dimer concentration 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.

6. Change From Baseline in Glucose [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate glucose 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.

7. Change From Baseline in Hemoglobin [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate hemoglobin 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.

8. Change From Baseline in Platelets [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate platelets 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.

9. Change From Baseline in Prothrombin International Normalized Ratio (INR) [Days 1, 3, 5, 8, 11, 15 and 29]

   Blood to evaluate INR 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.

10. Change From Baseline in Total Bilirubin [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate total bilirubin 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.

11. Change From Baseline in White Blood Cell Count (WBC) [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate WBC 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.

12. Change From Baseline in Neutrophils [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate neutrophils 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.

13. Change From Baseline in Lymphocytes [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate lymphocytes 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.

14. Change From Baseline in Monocytes [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate monocytes 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.

15. Change From Baseline in Basophils [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate basophils 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.

16. Change From Baseline in Eosinophils [Days 1, 3, 5, 8, 11, 15 and 29]

    Blood to evaluate eosinophils 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.

17. Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) [Day 1 through Day 29]

    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.

18. Percentage of Participants Reporting Serious Adverse Events (SAEs) [Day 1 through Day 29]

    An SAE is defined as an AE or suspected adverse reaction 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.

19. Days of Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) [Day 1 through Day 29]

    Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

20. Days of Non-invasive Ventilation/High Flow Oxygen [Day 1 through Day 29]

    Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

21. Duration of Supplemental Oxygen Use [Day 1 through Day 29]

    Duration of supplemental oxygen use was measured in days among participants who were on oxygen at baseline, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

22. Desirability of Outcome Ranking (DOOR) at Day 15 [Day 1 through Day 15]

    Desirability of Outcome Ranking (DOOR) based on ordinal scale: 1) Recovered (category 1, 2 or 3 on ordinal scale); 2) Improved (> / = 1 category improvement of ordinal scale compared with baseline) & no serious adverse event (SAE); 3) Improved (> / = 1 category improvement of the ordinal scale compared with baseline) & SAE (related or unrelated); 4) No change in ordinal scale from baseline & no SAE; 5) No change in ordinal scale from baseline & SAE (related or unrelated); 6) Worsening (> / = 1 category worse in ordinal scale from baseline); 7) Death.

23. Desirability of Outcome Ranking (DOOR) at Day 29 [Day 1 through Day 29]

    Desirability of Outcome Ranking (DOOR) based on ordinal scale: 1) Recovered (category 1, 2 or 3 on ordinal scale); 2) Improved (> / = 1 category improvement of ordinal scale compared with baseline) & no serious adverse event (SAE); 3) Improved (> / = 1 category improvement of the ordinal scale compared with baseline) & SAE (related or unrelated); 4) No change in ordinal scale from baseline & no SAE; 5) No change in ordinal scale from baseline & SAE (related or unrelated); 6) Worsening (> / = 1 category worse in ordinal scale from baseline); 7) Death.

24. Duration of Hospitalization [Day 1 through Day 29]

    Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

25. Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration [Day 1 through Day 10]

    Discontinuation or temporary suspension of study product administration, including participants who died or were discharged, was evaluated for each study product/placebo.

26. 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.

27. 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.

28. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 [Day 1]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

29. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 [Day 3]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

30. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 [Day 5]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

31. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 [Day 8]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

32. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 [Day 11]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

33. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 [Day 15]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

34. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 [Day 22]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

35. Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 [Day 29]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

36. Percentage of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories [Day 15]

    The ordinal scale categories are defined as: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

37. The Proportion of Participants Not Meeting Criteria for One of the Three Most Severe Ordinal Scale Categories at Any Time. [Day 1 through Day 29]

    The three most severe ordinal scale categories are: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices.

38. Time to an Improvement of One Category From Baseline Using an Ordinal Scale [Day 1 through Day 29]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use. Time to improvement by at least one category was determined for each participant.

39. Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale [Day 1 through Day 29]

    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use. Time to improvement by at least two categories was determined for each participant.

40. Time to Recovery [Day 1 through Day 29]

    Day of recovery is defined as the first day on which the participant satisfies one of the following three ordinal scale categories: 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Hospitalized with symptoms suggestive of COVID-19.

2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures and understands and agrees to comply with planned study procedures.

3. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.

4. 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. NAAT, antigen test) in any respiratory specimen or saliva < / = 14 days prior to randomization.

5. Within the 7 days prior to randomization requiring new use of supplemental oxygen (or increased oxygen requirement if on chronic oxygen) and requires at the time of randomization low or high flow oxygen devices or use of non-invasive mechanical ventilation (ordinal scale category 5 or 6).

6. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.

7. 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. Prior enrollment in ACTT-3 or ACTT-4. Note: this includes subjects whose participation in ACTT was terminated early.

2. On invasive mechanical ventilation at the time of randomization (ordinal scale category 7).

3. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of randomization.

4. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).

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

6. Subjects with an eGFR 15-30 mL/min are excluded unless in the opinion of the PI, the potential benefit of participation outweighs the potential risk of study participation.

7. All subjects with an eGFR <15 mL/min

8. All subjects on hemodialysis and/or hemofiltration at screening, irrespective of eGFR are excluded.

9. Neutropenia (absolute neutrophil count <700 cells/microliter, 0.7 x 10^3/microliter).

10. Lymphopenia (absolute lymphocyte count <200 cells/microliter, 0.20 x 10^3/microliter).

11. Received five or more doses of remdesivir including the loading dose, outside of the study as treatment for COVID-19.

12. Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day 1 until two weeks after the last study product is given are not excluded).

13. Allergy to any study medication.

14. Received convalescent plasma or intravenous immunoglobulin [IVIg] for COVID-19, the current illness for which they are being enrolled.

15. Received any of the following in the two weeks prior to screening as treatment of

COVID-19:

• More than one dose of baricitinib for the treatment of COVID-19;

• Other small molecule tyrosine kinase inhibitors (e.g. imatinib, gefitinib, acalabrutinib, etc.);

• monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.);

• monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19. Note: receipt of anti-SARS-CoV-2 monoclonal antibody (mAb) prior to enrollment (e.g. bamlanivimab) for their current COVID-19 illness is not exclusionary

1. Use of probenecid that cannot be discontinued at study enrollment.

2. Received 6 mg or more of dexamethasone by mouth (po) or Intravenous (IV) (or equivalent for other glucocorticoids) in one day, on more than one day, in the 7 days prior to time of randomization. Note: 6 mg dexamethasone dose equivalents include 40 mg prednisone, 32 mg methylprednisolone and 160 mg hydrocortisone.

3. Received > / = 20 mg/day of prednisone po or IV (or equivalent for other glucocorticoids) for > / = 14 consecutive days in the 4 weeks prior to screening.

4. Have diagnosis of current active or latent tuberculosis (TB), if known, treated for less than 4 weeks with appropriate therapy (by history only, no screening required).

5. Serious infection (besides COVID-19), immunosuppressive state, or immunosuppressive medications that in the opinion of the investigator could constitute a risk when taking baricitinib or dexamethasone.

6. Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations including SARS-CoV-2 vaccine is allowed for all subjects.

7. Had a known Venous thromboembolism (VTE)(deep vein thrombosis [DVT] or pulmonary embolism [PE]) during the current COVID-19 illness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham School of Medicine - Infectious Disease	Birmingham	Alabama	United States	35233
2	UCSF Fresno Center for Medical Education and Research - Clinical Research Center	Fresno	California	United States	93701
3	University of California San Diego Health - Jacobs Medical Center	La Jolla	California	United States	29037
4	University of California Los Angeles Medical Center - Westwood Clinic	Los Angeles	California	United States	90095
5	University of California Irvine Medical Center - Infectious Disease	Orange	California	United States	92868-3298
6	VA Palo Alto Health Care System - Infectious Diseases	Palo Alto	California	United States	94304-1207
7	University of California Davis Medical Center - Internal Medicine - Infectious Disease	Sacramento	California	United States	95817-1460
8	Kaiser Permanente San Diego Medical Center	San Diego	California	United States	92123
9	Naval Medical Center San Diego - Infectious Disease Clinic	San Diego	California	United States	92314
10	University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine	San Francisco	California	United States	94110-2859
11	Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases	Stanford	California	United States	94305-2200
12	Cedars Sinai Medical Center	West Hollywood	California	United States	90048-1804
13	VA Eastern Colorado Health Care System	Aurora	Colorado	United States	80045
14	Denver Health Division of Hospital Medicine - Main Campus	Denver	Colorado	United States	80204
15	Georgetown University Medical Center - Division of Infectious Diseases	Washington	District of Columbia	United States	20007
16	University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine	Gainesville	Florida	United States	32610
17	University of Florida Health - Jacksonville - Department of Emergency Medicine	Jacksonville	Florida	United States	32209
18	University of Miami Miller School of Medicine - Infectious Diseases	Miami	Florida	United States	33136
19	Emory Vaccine Center - The Hope Clinic	Decatur	Georgia	United States	30030-1705
20	Atlanta VA Medical Center - Infectious Diseases Clinic	Decatur	Georgia	United States	30033
21	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
22	Northwestern Hospital - Infectious Disease	Chicago	Illinois	United States	60611-2908
23	University of Illinois at Chicago College of Medicine - Division of Infectious Diseases	Chicago	Illinois	United States	60612
24	University of Iowa Hospitals & Clinics - Department of Internal Medicine	Iowa City	Iowa	United States	52242
25	Tulane University - Section of Pulmonary Diseases, Critical Care, and Environmental Medicine	New Orleans	Louisiana	United States	70112
26	University of Maryland School of Medicine - Center for Vaccine Development - Baltimore	Baltimore	Maryland	United States	21201-1509
27	Johns Hopkins Hospital - Medicine - Infectious Diseases	Baltimore	Maryland	United States	21287-0005
28	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889
29	National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section	Bethesda	Maryland	United States	20892-1504
30	Massachusetts General Hospital - Infectious Diseases	Boston	Massachusetts	United States	02114-2621
31	University of Massachusetts Medical School - Infectious Diseases and Immunology	Worcester	Massachusetts	United States	01655-0002
32	University of Michigan - Infectious Disease Clinic at Taubman Center	Ann Arbor	Michigan	United States	48109
33	University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine	Minneapolis	Minnesota	United States	55455-0341
34	Saint Louis University - Center for Vaccine Development	Saint Louis	Missouri	United States	63104-1015
35	University of Nebraska Medical Center - Infectious Diseases	Omaha	Nebraska	United States	68105
36	CHI Health Creighton University Medical Center - Bergan Mercy - Pulmonary Medicine	Omaha	Nebraska	United States	68124
37	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey	United States	07960
38	University of New Mexico Clinical and Translational Science Center	Albuquerque	New Mexico	United States	87106
39	Montefiore Medical Center - Infectious Diseases	Bronx	New York	United States	10467-2401
40	New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology	New York	New York	United States	10016-6402
41	University of Rochester Medical Center - Vaccine Research Unit	Rochester	New York	United States	14642-0001
42	Duke Human Vaccine Institute - Duke Vaccine and Trials Unit	Durham	North Carolina	United States	27704
43	Womack Army Medical Center - Pulmonary and Respiratory Services	Fort Bragg	North Carolina	United States	28310
44	University of Oklahoma Health Science Center - Surgery	Oklahoma City	Oklahoma	United States	73104
45	Kaiser Permanente Northwest - Center for Health Research	Portland	Oregon	United States	97227
46	Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases	Hershey	Pennsylvania	United States	17033
47	Hospital of the University of Pennsylvania - Infectious Diseases	Philadelphia	Pennsylvania	United States	19104-4238
48	University of Pittsburgh - Medicine - Infectious Diseases	Pittsburgh	Pennsylvania	United States	15213-2582
49	Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants	Dallas	Texas	United States	75246
50	University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases	Dallas	Texas	United States	75390-8884
51	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
52	University of Texas Medical Branch - Division of Infectious Disease	Galveston	Texas	United States	77555-0435
53	Methodist Hospital - Houston	Houston	Texas	United States	77030-2703
54	Baylor College of Medicine - Molecular Virology and Microbiology	Houston	Texas	United States	77030-3411
55	University of Texas Health Science Center at San Antonio - Infectious Diseases	San Antonio	Texas	United States	78229-3901
56	University of Utah - Infectious Diseases	Salt Lake City	Utah	United States	84132-0002
57	University of Virginia - Acute Care Surgery	Charlottesville	Virginia	United States	22908-0816
58	Naval Medical Center Portsmouth - Infectious Disease Division	Portsmouth	Virginia	United States	23708
59	EvergreenHealth Infectious Disease Service	Kirkland	Washington	United States	98034
60	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
61	Madigan Army Medical Center - Infectious Disease Clinic	Tacoma	Washington	United States	98431
62	Tokyo Medical and Dental University - Medical Hospital - Department of Respiratory Medicine	Tokyo		Japan	113-8519
63	National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center	Tokyo		Japan	162-8655
64	Seoul National University Bundang Hospital - Division of Infectious Diseases	Bundang-gu Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
65	Seoul National University Hospital	Seoul	Jongno-gu	Korea, Republic of	03080
66	Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia	Mexico City		Mexico	14080
67	Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas	Mexico City		Mexico	14080
68	National University Health System - Division of Infectious Diseases	Singapore		Singapore	119228
69	National University Health System - Alexandra Hospital - Division of Infectious Diseases	Singapore		Singapore	159964
70	National Centre for Infectious Diseases	Singapore		Singapore	308442
71	Changi General Hospital - Clinical Trials and Research Unit (CTRU)	Singapore		Singapore	529889
72	Ng Teng Fong General Hospital - Infectious Disease Service	Singapore		Singapore	609606

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2021
• Statistical Analysis Plan - Jun 9, 2021
• Informed Consent Form - Jan 22, 2021

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT04640168
• Other Study ID Numbers: 20-0006 ACTT-4
• First Posted: Nov 23, 2020
• Last Update Posted: Jun 28, 2022
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): ACTT; Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety
• Additional relevant MeSH terms: COVID-19; Remdesivir; Dexamethasone

Study Results

Participant Flow

Recruitment Details	Participants were recruited at the participating sites from those admitted with symptoms of COVID-19 confirmed by PCR. Enrollment occurred between December 2, 2020 and April 13, 2021.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course. Baricitinib: Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name [1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile. Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide. Placebo: Placebo matching intravenous dexamethasone. Remdesivir: Drug remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course. Dexamethasone: Dexamethasone Sodium Phosphate Injection, USP, is an adrenocortical steroid anti-inflammatory drug. It is a water-soluble inorganic ester of dexamethasone. Each mL contains dexamethasone sodium phosphate equivalent to dexamethasone phosphate 4 mg or dexamethasone 3.33 mg; benzyl alcohol 10 mg added as preservative; sodium citrate dihydrate 11 mg; sodium sulfite 1 mg as an antioxidant. Placebo: Placebo matching oral baricitinib. Remdesivir: Drug remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Period Title: Overall Study
STARTED	516	494
Treated	503	482
ITT and Modified ITT Population	516	494
As Treated Population	503	482
COMPLETED	495	475
NOT COMPLETED	21	19

Baseline Characteristics

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone	Total
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	Total of all reporting groups
Overall Participants	516	494	1010
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	345 66.9%	330 66.8%	675 66.8%
>=65 years	171 33.1%	164 33.2%	335 33.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.2 (14.3)	58.5 (13.7)	58.3 (14.0)
Sex: Female, Male (Count of Participants)
Female	216 41.9%	204 41.3%	420 41.6%
Male	300 58.1%	290 58.7%	590 58.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	188 36.4%	159 32.2%	347 34.4%
Not Hispanic or Latino	318 61.6%	318 64.4%	636 63%
Unknown or Not Reported	10 1.9%	17 3.4%	27 2.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	8 1.6%	10 2%	18 1.8%
Asian	35 6.8%	35 7.1%	70 6.9%
Native Hawaiian or Other Pacific Islander	1 0.2%	4 0.8%	5 0.5%
Black or African American	94 18.2%	94 19%	188 18.6%
White	307 59.5%	281 56.9%	588 58.2%
More than one race	3 0.6%	2 0.4%	5 0.5%
Unknown or Not Reported	68 13.2%	68 13.8%	136 13.5%
Region of Enrollment (participants) [Number]
South Korea	13 2.5%	11 2.2%	24 2.4%
Singapore	2 0.4%	2 0.4%	4 0.4%
United States	474 91.9%	453 91.7%	927 91.8%
Japan	0 0%	3 0.6%	3 0.3%
Mexico	27 5.2%	25 5.1%	52 5.1%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)
Description	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 as of Day 29. Results are reported as Kaplan Meier estimates.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized. mITT participants were classified by their randomized treatment assignment and their baseline ordinal score, which is not necessarily equivalent to the disease severity stratum to which the participant was randomized at enrollment. One participant was excluded from mITT analyses due to a baseline ordinal score of 4.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Number (95% Confidence Interval) [Proportion of participants]	0.87 0.2%	0.88 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.909
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Change From Baseline in Alanine Aminotransferase (ALT)
Description	Blood to evaluate ALT 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	483	458
Day 3	1.1	4.3
Day 5	6.0	15.9
Day 8	4.7	16.1
Day 11	5.6	15.5
Day 15	7.1	8.2
Day 29	-3.8	1.1

3. Secondary Outcome

Title	Change From Baseline in Aspartate Aminotransferase (AST)
Description	Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	482	458
Day 3	-5.9	-7.2
Day 5	-4.0	-8.5
Day 8	-10.8	-12.0
Day 11	-12.1	-16.4
Day 15	-13.4	-15.4
Day 29	-18.6	9.9

4. Secondary Outcome

Title	Change From Baseline in C-reactive Protein (CRP)
Description	Blood to evaluate CRP 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants by their randomized treatment assignment and baseline ordinal score. For missing data, if results were available for visits before or after that visit, the average of the two nearest visits was imputed. If a participant died or was lost to follow-up, their last available observation was carried forward. If baseline was missing, the earliest post-treatment dose was used. Participants from sites reporting high sensitivity CRP were excluded.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	437	415
Day 3	-41.1	-61.0
Day 5	-39.4	-73.6
Day 8	-53.0	-79.0
Day 11	-61.6	-81.6
Day 15	-73.2	-81.1
Day 29	-78.6	-84.1

5. Secondary Outcome

Title	Change From Baseline in Creatinine
Description	Blood to evaluate serum creatinine 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	484	461
Day 3	-0.207	-0.081
Day 5	-0.287	-0.122
Day 8	-0.434	-0.096
Day 11	0.007	-0.102
Day 15	-0.011	-0.024
Day 29	-0.064	-0.029

6. Secondary Outcome

Title	Change From Baseline in D-dimer Concentration
Description	Blood to evaluate d-dimer concentration 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants by their randomized treatment assignment and baseline ordinal score. For any missing data, if results were available for visits before or after that visit, the average of the two nearest visits was imputed for all missing visits between them. If a participant died or was lost to follow-up, their last available observation was carried forward. If baseline was missing, another pre-treatment dose was used, or the earliest post-treatment dose was used.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	490	467
Day 3	0.8	0.2
Day 5	0.7	0.7
Day 8	0.7	0.9
Day 11	0.7	0.5
Day 15	0.1	0.3
Day 29	0.1	0.2

7. Secondary Outcome

Title	Change From Baseline in Glucose
Description	Blood to evaluate glucose 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	484	461
Day 3	-46.9	3.8
Day 5	-43.2	-6.7
Day 8	-35.0	-9.6
Day 11	-28.1	-15.0
Day 15	-26.0	-20.2
Day 29	-28.9	-25.4

8. Secondary Outcome

Title	Change From Baseline in Hemoglobin
Description	Blood to evaluate hemoglobin 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	481	458
Day 3	-0.51	-0.25
Day 5	-0.64	-0.13
Day 8	-1.08	-0.15
Day 11	-1.44	-0.76
Day 15	-0.97	-0.91
Day 29	-0.51	-0.66

9. Secondary Outcome

Title	Change From Baseline in Platelets
Description	Blood to evaluate platelets 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	479	456
Day 3	53.1	70.4
Day 5	107.4	117.6
Day 8	178.9	140.4
Day 11	193.9	105.0
Day 15	139.6	45.3
Day 29	35.3	69.4

10. Secondary Outcome

Title	Change From Baseline in Prothrombin International Normalized Ratio (INR)
Description	Blood to evaluate INR 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	445	412
Day 3	0.06	-0.01
Day 5	0.11	-0.03
Day 8	0.11	-0.08
Day 11	0.09	-0.14
Day 15	0.00	-0.04
Day 29	-0.06	-0.05

11. Secondary Outcome

Title	Change From Baseline in Total Bilirubin
Description	Blood to evaluate total bilirubin 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	482	458
Day 3	0.00	-0.09
Day 5	0.06	-0.03
Day 8	0.03	0.03
Day 11	0.04	0.05
Day 15	-0.01	0.03
Day 29	-0.02	-0.05

12. Secondary Outcome

Title	Change From Baseline in White Blood Cell Count (WBC)
Description	Blood to evaluate WBC 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	481	458
Day 3	0.433	1.292
Day 5	1.358	2.072
Day 8	2.629	4.048
Day 11	4.153	5.179
Day 15	1.638	2.386
Day 29	0.688	0.116

13. Secondary Outcome

Title	Change From Baseline in Neutrophils
Description	Blood to evaluate neutrophils 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	477	451
Day 3	-0.500	0.974
Day 5	0.356	1.407
Day 8	1.421	3.227
Day 11	2.937	4.135
Day 15	0.416	1.229
Day 29	-0.659	-1.239

14. Secondary Outcome

Title	Change From Baseline in Lymphocytes
Description	Blood to evaluate lymphocytes 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	477	451
Day 3	0.766	0.142
Day 5	0.627	0.356
Day 8	0.614	0.317
Day 11	0.594	0.372
Day 15	0.693	0.621
Day 29	0.842	0.996

15. Secondary Outcome

Title	Change From Baseline in Monocytes
Description	Blood to evaluate monocytes 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	477	450
Day 3	0.114	0.120
Day 5	0.164	0.180
Day 8	0.257	0.221
Day 11	0.367	0.306
Day 15	0.295	0.286
Day 29	0.171	0.159

16. Secondary Outcome

Title	Change From Baseline in Basophils
Description	Blood to evaluate basophils 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	471	446
Day 3	0.008	0.000
Day 5	0.016	0.004
Day 8	0.015	0.006
Day 11	0.021	0.006
Day 15	0.035	0.030
Day 29	0.043	0.046

17. Secondary Outcome

Title	Change From Baseline in Eosinophils
Description	Blood to evaluate eosinophils 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.
Time Frame	Days 1, 3, 5, 8, 11, 15 and 29

Outcome Measure Data

Analysis Population Description

The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	472	446
Day 3	0.034	-0.006
Day 5	0.104	0.006
Day 8	0.115	0.027
Day 11	0.116	0.034
Day 15	0.124	0.119
Day 29	0.208	0.211

18. Secondary Outcome

Title	Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)
Description	Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The safety population includes all participants with available data post baseline, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	503	482
Number [percentage of participants]	28.4 5.5%	36.1 7.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; 1.8 to 13.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Percentage of Participants Reporting Serious Adverse Events (SAEs)
Description	An SAE is defined as an AE or suspected adverse reaction 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 29

Outcome Measure Data

Analysis Population Description

The safety population includes all participants with available data post baseline, analyzed as treated.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	503	482
Number [percentage of participants]	18.9 3.7%	19.5 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -4.3 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Days of Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO)
Description	Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The analysis population is restricted to randomized participants who were on invasive ventilation.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	55	47
Including imputations for participants who died	27	28
Among participants who did not die	14	15

21. Secondary Outcome

Title	Days of Non-invasive Ventilation/High Flow Oxygen
Description	Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The analysis population is restricted to randomized participants who were not on noninvasive ventilation or high-flow oxygen at baseline but who subsequently required non-invasive or high-flow oxygen.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	69	88
Including imputations for participants who died	5	8
Among participants who did not die	4	6

22. Secondary Outcome

Title	Duration of Supplemental Oxygen Use
Description	Duration of supplemental oxygen use was measured in days among participants who were on oxygen at baseline, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The analysis population is restricted to randomized participants who were on oxygen at baseline.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Including imputations for participants who died	10	10.5
Among participants who did not die	9	8

23. Secondary Outcome

Title	Desirability of Outcome Ranking (DOOR) at Day 15
Description	Desirability of Outcome Ranking (DOOR) based on ordinal scale: 1) Recovered (category 1, 2 or 3 on ordinal scale); 2) Improved (> / = 1 category improvement of ordinal scale compared with baseline) & no serious adverse event (SAE); 3) Improved (> / = 1 category improvement of the ordinal scale compared with baseline) & SAE (related or unrelated); 4) No change in ordinal scale from baseline & no SAE; 5) No change in ordinal scale from baseline & SAE (related or unrelated); 6) Worsening (> / = 1 category worse in ordinal scale from baseline); 7) Death.
Time Frame	Day 1 through Day 15

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
1 - Recovered (Category 1, 2 or 3 Clinical Status)	76 14.7%	77 15.6%
2 - Improved (=1 category improvement in Clinical Status compared with baseline) & no SAE	3 0.6%	1 0.2%
3 - Improved (=1 category improvement compared with baseline) & SAE (related or unrelated)	1 0.2%	2 0.4%
4 - No change in Clinical Status from baseline & no SAE	7 1.4%	6 1.2%
5 - No change in Clinical Status from baseline & SAE (related or unrelated)	3 0.6%	2 0.4%
6 - Worsening (=1 category worse in Clinical Status compared with baseline)	7 1.4%	10 2%
7 - Death	3 0.6%	3 0.6%

24. Secondary Outcome

Title	Desirability of Outcome Ranking (DOOR) at Day 29
Description	Desirability of Outcome Ranking (DOOR) based on ordinal scale: 1) Recovered (category 1, 2 or 3 on ordinal scale); 2) Improved (> / = 1 category improvement of ordinal scale compared with baseline) & no serious adverse event (SAE); 3) Improved (> / = 1 category improvement of the ordinal scale compared with baseline) & SAE (related or unrelated); 4) No change in ordinal scale from baseline & no SAE; 5) No change in ordinal scale from baseline & SAE (related or unrelated); 6) Worsening (> / = 1 category worse in ordinal scale from baseline); 7) Death.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
1 - Recovered (Category 1, 2 or 3 Clinical Status)	85 16.5%	84 17%
2 - Improved (=1 category improvement in Clinical Status compared with baseline) & no SAE	0.002 0%	0.002 0%
3 - Improved (=1 category improvement compared with baseline) & SAE (related or unrelated)	1 0.2%	1 0.2%
4 - No change in Clinical Status from baseline & no SAE	3 0.6%	3 0.6%
5 - No change in Clinical Status from baseline & SAE (related or unrelated)	1 0.2%	1 0.2%
6 - Worsening (=1 category worse in Clinical Status compared with baseline)	3 0.6%	4 0.8%
7 - Death	5 1%	7 1.4%

25. Secondary Outcome

Title	Duration of Hospitalization
Description	Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (ITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Including imputations for participants who died	7	6
Among participants who did not die	6	6

26. Secondary Outcome

Title	Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration
Description	Discontinuation or temporary suspension of study product administration, including participants who died or were discharged, was evaluated for each study product/placebo.
Time Frame	Day 1 through Day 10

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	516	494
Remdesivir	460 89.1%	444 89.9%
Baricitinib/Placebo	486 94.2%	452 91.5%
Dexamethasone/placebo	410 79.5%	387 78.3%

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	516	494
Number (95% Confidence Interval) [Proportion of participants]	0.03 0%	0.02 0%

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	516	494
Number (95% Confidence Interval) [Proportion of participants]	0.05 0%	0.06 0%

29. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

The mITT population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	0.2 0%	0.0 0%
7) Hospitalized, on invasive mechanical ventilation or ECMO	0.0 0%	0.0 0%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	16.1 3.1%	14.2 2.9%
5) Hospitalized, requiring supplemental oxygen	83.7 16.2%	85.8 17.4%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	0.0 0%	0.0 0%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	0.0 0%	0.0 0%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	0.0 0%	0.0 0%
1) Not hospitalized, no limitations on activities	0.0 0%	0.0 0%

30. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	0.4 0.1%	0.4 0.1%
7) Hospitalized, on invasive mechanical ventilation or ECMO	3.1 0.6%	1.0 0.2%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	22.1 4.3%	21.5 4.4%
5) Hospitalized, requiring supplemental oxygen	71.7 13.9%	73.5 14.9%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	2.7 0.5%	3.2 0.6%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	0.0 0%	0.0 0%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	0.0 0%	0.4 0.1%
1) Not hospitalized, no limitations on activities	0.0 0%	0.0 0%

31. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	0.6 0.1%	0.4 0.1%
7) Hospitalized, on invasive mechanical ventilation or ECMO	5.2 1%	3.4 0.7%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	19.4 3.8%	20.9 4.2%
5) Hospitalized, requiring supplemental oxygen	53.4 10.3%	49.2 10%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	9.5 1.8%	11.9 2.4%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	1.2 0.2%	0.6 0.1%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	10.7 2.1%	13.2 2.7%
1) Not hospitalized, no limitations on activities	0.0 0%	0.4 0.1%

32. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	1.2 0.2%	0.8 0.2%
7) Hospitalized, on invasive mechanical ventilation or ECMO	7.4 1.4%	6.1 1.2%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	12.2 2.4%	14.6 3%
5) Hospitalized, requiring supplemental oxygen	24.9 4.8%	24.5 5%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	6.4 1.2%	5.7 1.2%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	1.4 0.3%	1.4 0.3%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	46.4 9%	47.0 9.5%
1) Not hospitalized, no limitations on activities	0.2 0%	0.0 0%

33. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 11

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	2.1 0.4%	1.2 0.2%
7) Hospitalized, on invasive mechanical ventilation or ECMO	7.8 1.5%	6.9 1.4%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	6.6 1.3%	9.1 1.8%
5) Hospitalized, requiring supplemental oxygen	14.4 2.8%	11.1 2.2%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	2.7 0.5%	3.2 0.6%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	1.4 0.3%	0.4 0.1%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	63.5 12.3%	66.4 13.4%
1) Not hospitalized, no limitations on activities	1.6 0.3%	1.6 0.3%

34. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	3.1 0.6%	2.6 0.5%
7) Hospitalized, on invasive mechanical ventilation or ECMO	6.2 1.2%	6.1 1.2%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	3.7 0.7%	5.3 1.1%
5) Hospitalized, requiring supplemental oxygen	9.3 1.8%	7.9 1.6%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	1.9 0.4%	1.2 0.2%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	1.0 0.2%	0.4 0.1%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	51.5 10%	53.6 10.9%
1) Not hospitalized, no limitations on activities	23.3 4.5%	22.9 4.6%

35. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 22

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	4.9 0.9%	4.9 1%
7) Hospitalized, on invasive mechanical ventilation or ECMO	4.3 0.8%	4.9 1%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	2.1 0.4%	2.8 0.6%
5) Hospitalized, requiring supplemental oxygen	5.4 1%	5.5 1.1%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	0.8 0.2%	0.2 0%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	0.0 0%	0.2 0%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	48.0 9.3%	48.0 9.7%
1) Not hospitalized, no limitations on activities	34.6 6.7%	33.6 6.8%

36. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, participant is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	5.4 1%	6.9 1.4%
7) Hospitalized, on invasive mechanical ventilation or ECMO	2.7 0.5%	2.6 0.5%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	2.3 0.4%	2.6 0.5%
5) Hospitalized, requiring supplemental oxygen	4.1 0.8%	3.4 0.7%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	0.6 0.1%	0.4 0.1%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	0.0 0%	0.0 0%
2) Not hospitalized, but has new or increased limitation on activities and/or need for oxygen	57.3 11.1%	52.0 10.5%
1) Not hospitalized, no limitations on activities	27.6 5.3%	32.0 6.5%

37. Secondary Outcome

Title	Percentage of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories
Description	The ordinal scale categories are defined as: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
8) Death	3 0.6%	3 0.6%
7) Hospitalized, on invasive mechanical ventilation or ECMO	6 1.2%	6 1.2%
6) Hospitalized, on non-invasive ventilation or high flow oxygen devices	4 0.8%	5 1%
5) Hospitalized, requiring supplemental oxygen	9 1.7%	8 1.6%
4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care	2 0.4%	1 0.2%
3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care	1 0.2%	0.4 0.1%
2) Not hospitalized, but has new or increased limitation on activities and/or new oxygen use	51 9.9%	54 10.9%
1) Not hospitalized, no limitations on activities	23 4.5%	23 4.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Secondary Outcome

Title	The Proportion of Participants Not Meeting Criteria for One of the Three Most Severe Ordinal Scale Categories at Any Time.
Description	The three most severe ordinal scale categories are: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	432	424
Number (95% Confidence Interval) [Proportion of participants]	0.81 0.2%	0.78 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Time to an Improvement of One Category From Baseline Using an Ordinal Scale
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use. Time to improvement by at least one category was determined for each participant.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Median (95% Confidence Interval) [Days]	5.0	4.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale
Description	The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use. Time to improvement by at least two categories was determined for each participant.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Median (95% Confidence Interval) [Days]	6.0	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Secondary Outcome

Title	Time to Recovery
Description	Day of recovery is defined as the first day on which the participant satisfies one of the following three ordinal scale categories: 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized, classified by their randomized treatment assignment.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Median (Inter-Quartile Range) [Days]	6.0	5.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remdesivir Plus Baricitinib, Remdesivir Plus Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

42. Primary Outcome

Title	The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Race
Description	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 as of Day 29. Results are reported as Kaplan Meier estimates.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized. mITT participants were classified by their randomized treatment assignment and their baseline ordinal score, which is not necessarily equivalent to the disease severity stratum to which the participant was randomized at enrollment. One participant was excluded from mITT analyses due to a baseline ordinal score of 4.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Asian	0.76 0.1%	0.88 0.2%
Black or African American	0.91 0.2%	0.86 0.2%
White	0.87 0.2%	0.88 0.2%
Other	0.87 0.2%	0.89 0.2%

43. Primary Outcome

Title	The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Ethnicity
Description	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 as of Day 29. Results are reported as Kaplan Meier estimates.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized and for whom ethnicity was reported. mITT participants were classified by their randomized treatment assignment and their baseline ordinal score, which is not necessarily equivalent to the disease severity stratum to which the participant was randomized at enrollment. One participant was excluded from mITT analyses due to a baseline ordinal score of 4.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	505	477
Not Hispanic or Latino	0.87 0.2%	0.87 0.2%
Hispanic or Latino	0.88 0.2%	0.87 0.2%

44. Primary Outcome

Title	The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Sex
Description	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 as of Day 29. Results are reported as Kaplan Meier estimates.
Time Frame	Day 1 through Day 29

Outcome Measure Data

Analysis Population Description

The modified intention-to-treat (mITT) population includes all participants who were randomized. mITT participants were classified by their randomized treatment assignment and their baseline ordinal score, which is not necessarily equivalent to the disease severity stratum to which the participant was randomized at enrollment. One participant was excluded from mITT analyses due to a baseline ordinal score of 4.

Arm/Group Title	Remdesivir Plus Baricitinib	Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
Measure Participants	515	494
Male	0.86 0.2%	0.87 0.2%
Female	0.89 0.2%	0.88 0.2%

Adverse Events

Time Frame	Serious and Grade 3 and 4 non-serious adverse events were collected for 29 days after the first dose. Laboratory values were systematically assessed at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29. Treatment emergent and fatal AEs are reported.
Adverse Event Reporting Description	Given the severity of underlying illness, participants were expected to have many symptoms and abnormalities in vital signs and laboratory values. All Grade 3 and 4 AEs were captured as AEs in this trial. Grade 2 or higher, suspected drug-related hypersensitivity reaction or deep vein thrombosis or pulmonary embolism of any grade was reported as an AE in this trial. All cause mortality was calculated for the ITT population, while SAEs and AEs reflect the as treated population.
Arm/Group Title	Remdesivir Plus Baricitinib		Remdesivir Plus Dexamethasone
Arm/Group Description	200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; 4 mg of baricitinib administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and dexamethasone placebo administered as an intravenous injection daily while hospitalized for up to a 10-day total course.		200 mg of remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of remdesivir while hospitalized for up to a 10-day total course; baricitinib placebo administered as 2 tablets taken orally daily while hospitalized for up to a 14-day total course; and 6 mg of dexamethasone administered as an intravenous injection daily while hospitalized for up to a 10-day total course.
All Cause Mortality
	Remdesivir Plus Baricitinib		Remdesivir Plus Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/516 (5.4%)		34/494 (6.9%)
Serious Adverse Events
	Remdesivir Plus Baricitinib		Remdesivir Plus Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/503 (18.9%)		94/482 (19.5%)
Blood and lymphatic system disorders
Anaemia	1/503 (0.2%)	1	1/482 (0.2%)	1
Hypercoagulation	1/503 (0.2%)	1	0/482 (0%)	0
Lymphopenia	2/503 (0.4%)	2	3/482 (0.6%)	3
Thrombocytopenia	0/503 (0%)	0	1/482 (0.2%)	1
Cardiac disorders
Acute myocardial infarction	0/503 (0%)	0	1/482 (0.2%)	1
Arrhythmia	1/503 (0.2%)	1	1/482 (0.2%)	1
Atrial fibrillation	0/503 (0%)	0	1/482 (0.2%)	1
Bradycardia	0/503 (0%)	0	1/482 (0.2%)	1
Cardiac arrest	2/503 (0.4%)	2	2/482 (0.4%)	2
Cardio-respiratory arrest	2/503 (0.4%)	2	0/482 (0%)	0
Myocardial infarction	0/503 (0%)	0	2/482 (0.4%)	2
Sinus bradycardia	1/503 (0.2%)	1	0/482 (0%)	0
Supraventricular tachycardia	0/503 (0%)	0	2/482 (0.4%)	2
Eye disorders
Retinal artery occlusion	1/503 (0.2%)	1	0/482 (0%)	0
Gastrointestinal disorders
Colitis	1/503 (0.2%)	1	0/482 (0%)	0
Dysphagia	1/503 (0.2%)	1	0/482 (0%)	0
Gastrointestinal haemorrhage	1/503 (0.2%)	1	1/482 (0.2%)	1
General disorders
Multiple organ dysfunction syndrome	2/503 (0.4%)	2	7/482 (1.5%)	7
Systemic inflammatory response syndrome	1/503 (0.2%)	1	0/482 (0%)	0
Infections and infestations
COVID-19	0/503 (0%)	0	1/482 (0.2%)	1
Cellulitis	1/503 (0.2%)	1	0/482 (0%)	0
Fungal sepsis	0/503 (0%)	0	1/482 (0.2%)	1
Gastroenteritis	0/503 (0%)	0	1/482 (0.2%)	1
Pneumonia	8/503 (1.6%)	8	3/482 (0.6%)	3
Pneumonia bacterial	3/503 (0.6%)	3	3/482 (0.6%)	3
Pneumonia klebsiella	1/503 (0.2%)	1	0/482 (0%)	0
Sepsis	3/503 (0.6%)	4	4/482 (0.8%)	4
Septic shock	6/503 (1.2%)	6	2/482 (0.4%)	2
Urinary tract infection	0/503 (0%)	0	1/482 (0.2%)	1
Injury, poisoning and procedural complications
Femur fracture	0/503 (0%)	0	1/482 (0.2%)	1
Infusion related reaction	1/503 (0.2%)	1	0/482 (0%)	0
Investigations
Glomerular filtration rate decreased	2/503 (0.4%)	2	2/482 (0.4%)	2
Haemoglobin decreased	0/503 (0%)	0	1/482 (0.2%)	1
Hepatic enzyme increased	1/503 (0.2%)	1	0/482 (0%)	0
Transaminases increased	1/503 (0.2%)	1	1/482 (0.2%)	1
Metabolism and nutrition disorders
Failure to thrive	2/503 (0.4%)	2	3/482 (0.6%)	3
Hyperglycaemia	0/503 (0%)	0	1/482 (0.2%)	1
Nervous system disorders
Cerebral haemorrhage	1/503 (0.2%)	1	0/482 (0%)	0
Cerebrovascular accident	3/503 (0.6%)	3	0/482 (0%)	0
Dizziness	1/503 (0.2%)	1	0/482 (0%)	0
Ischaemic neuropathy	1/503 (0.2%)	1	0/482 (0%)	0
Ischaemic stroke	0/503 (0%)	0	1/482 (0.2%)	1
Seizure	0/503 (0%)	0	1/482 (0.2%)	1
Psychiatric disorders
Delirium	1/503 (0.2%)	1	0/482 (0%)	0
Substance use disorder	1/503 (0.2%)	1	0/482 (0%)	0
Suicidal ideation	0/503 (0%)	0	1/482 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	9/503 (1.8%)	9	4/482 (0.8%)	4
Renal failure	2/503 (0.4%)	2	0/482 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/503 (0.4%)	2	0/482 (0%)	0
Acute respiratory failure	12/503 (2.4%)	12	16/482 (3.3%)	16
Dyspnoea	0/503 (0%)	0	1/482 (0.2%)	1
Hypoxia	2/503 (0.4%)	2	4/482 (0.8%)	4
Interstitial lung disease	0/503 (0%)	0	1/482 (0.2%)	1
Pneumomediastinum	1/503 (0.2%)	1	0/482 (0%)	0
Pneumonia aspiration	1/503 (0.2%)	1	1/482 (0.2%)	1
Pneumothorax	1/503 (0.2%)	1	1/482 (0.2%)	1
Pulmonary embolism	10/503 (2%)	10	8/482 (1.7%)	8
Respiratory distress	5/503 (1%)	5	10/482 (2.1%)	10
Respiratory failure	52/503 (10.3%)	52	40/482 (8.3%)	40
Vascular disorders
Deep vein thrombosis	1/503 (0.2%)	1	0/482 (0%)	0
Hypotension	2/503 (0.4%)	2	0/482 (0%)	0
Shock	1/503 (0.2%)	1	2/482 (0.4%)	2
Other (Not Including Serious) Adverse Events
	Remdesivir Plus Baricitinib		Remdesivir Plus Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/503 (3.2%)		34/482 (7.1%)
Investigations
Lymphocyte count decreased	16/503 (3.2%)	17	34/482 (7.1%)	38

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.