Trial Outcomes & Findings for Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection (COVID-19) (NCT NCT04487886)

NCT ID: NCT04487886

Last Updated: 2023-04-07

Results Overview

This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 47 participants
• Primary outcome timeframe: Up to Day 29
• Results posted on: 2023-04-07

Participant Flow

Participants were recruited at Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began November 18, 2020 and all follow-up assessments were completed by June 10, 2021.

Participant milestones

Measure	Duvelisib Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days. Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.	Placebo Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Overall Study STARTED	25	22
Overall Study COMPLETED	25	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection (COVID-19)

Baseline characteristics by cohort

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.	Total n=47 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	56.1 years STANDARD_DEVIATION 12.2 • n=5 Participants	58.9 years STANDARD_DEVIATION 17.1 • n=7 Participants	57.4 years STANDARD_DEVIATION 14.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 29

This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Participants Requiring Mechanical Ventilation or Dying	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to Day 29

Population: This analysis includes participants who recovered; one participant in the placebo study arm passed away and is not included in this analysis.

Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=21 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Days to Recovery	6.00 days Standard Deviation 6.19	5.29 days Standard Deviation 4.19

SECONDARY outcome

Timeframe: Up to Day 29

The number of days spent hospitalized is presented for both study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Duration of Hospitalization	6.72 days Standard Deviation 7.48	6.95 days Standard Deviation 6.41

SECONDARY outcome

Timeframe: Up to Day 29

The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Days on Study Drug	4.6 days Standard Deviation 3.55	5.18 days Standard Deviation 2.77

SECONDARY outcome

Timeframe: Up to Day 29

The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Total Doses of Study Drug	7.76 drug doses Standard Deviation 6.79	8.91 drug doses Standard Deviation 5.61

SECONDARY outcome

Timeframe: Up to Day 29

The incidence of death within 29 days of randomization is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Participants Dying	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 29

The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Participants Transferred to ICU	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Between Day 14 and 28, Between Day 29 and 60

Population: This analysis includes participants who were able to be contacted for this assessment, or those with relevant information in the medical chart.

The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.

Outcome measures

Measure	Duvelisib n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Eastern Cooperative Oncology Group (ECOG) Performance Status Score Single assessment between Day 14 and 28	2 score on a scale Standard Deviation 1.01	1.5 score on a scale Standard Deviation 1.04
Eastern Cooperative Oncology Group (ECOG) Performance Status Score Single assessment between Day 29 and 60	1 score on a scale Standard Deviation 0.69	1 score on a scale Standard Deviation 1.04

SECONDARY outcome

Timeframe: Up to Day 29

The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Grade III-V Adverse Events	6 grade III-V adverse events	3 grade III-V adverse events

SECONDARY outcome

Timeframe: Up to Day 29

The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Secondary Bacterial or Viral Infections Count of bacterial infections	0 infections	1 infections
Number of Secondary Bacterial or Viral Infections Count of viral infections	0 infections	0 infections

SECONDARY outcome

Timeframe: Week 1, Week 2

The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
T Helper 1 (Th1) T Cell Frequency Week 1	19.52 percentage of CD4 T cells Standard Deviation 4.77	20.14 percentage of CD4 T cells Standard Deviation 7.52
T Helper 1 (Th1) T Cell Frequency Week 2	19.98 percentage of CD4 T cells Standard Deviation 6.24	18.27 percentage of CD4 T cells Standard Deviation 6.8

SECONDARY outcome

Timeframe: Week 1, Week 2

The mean frequency of Th17 T cells in PBMCs is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Th17 T Cell Frequency Week 1	2.24 percentage of CD4 T cells Standard Deviation 4.65	3.43 percentage of CD4 T cells Standard Deviation 3.78
Th17 T Cell Frequency Week 2	3.16 percentage of CD4 T cells Standard Deviation 2.44	4.25 percentage of CD4 T cells Standard Deviation 3.21

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-2 (IL-2) Levels Week 1	0.08723 pg/mL Standard Deviation 18.065	62.8596 pg/mL Standard Deviation 18.171
Interleukin-2 (IL-2) Levels Week 2	17.3632 pg/mL Standard Deviation 40.588	0.3158 pg/mL Standard Deviation 32.3258

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-2 Receptor (IL-2R) Levels Week 1	1172.80 pg/mL Standard Deviation 529.75	3569.93 pg/mL Standard Deviation 540.08
Interleukin-2 Receptor (IL-2R) Levels Week 2	912.47 pg/mL Standard Deviation 976.08	2005.94 pg/mL Standard Deviation 1207.7

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-6 (IL-6) Levels Week 1	7.9388 pg/mL Standard Deviation 41.3498	149.73 pg/mL Standard Deviation 42.0497
Interleukin-6 (IL-6) Levels Week 2	14.2294 pg/mL Standard Deviation 75.829	52.2227 pg/mL Standard Deviation 94.026

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-7 (IL-7) Levels Week 1	4.6018 pg/mL Standard Deviation 54.6831	198.80 pg/mL Standard Deviation 55.2375
Interleukin-7 (IL-7) Levels Week 2	3.2255 pg/mL Standard Deviation 98.8781	48.5118 pg/mL Standard Deviation 123.46

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-8 (IL-8) Levels Week 2	3.4120 pg/mL Standard Deviation 51.3241	26.6383 pg/mL Standard Deviation 63.927
Interleukin-8 (IL-8) Levels Week 1	3.1109 pg/mL Standard Deviation 28.2498	104.03 pg/mL Standard Deviation 28.5967

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interleukin-10 (IL-10) Levels Week 1	389.02 pg/mL Standard Deviation 838.50	808.09 pg/mL Standard Deviation 831.24
Interleukin-10 (IL-10) Levels Week 2	658.17 pg/mL Standard Deviation 1411.11	250.00 pg/mL Standard Deviation 1836.14

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Interferon Gamma-induced Protein 10 (IP-10) Levels Week 1	3136.50 pg/mL Standard Deviation 652.84	4781.42 pg/mL Standard Deviation 649.35
Interferon Gamma-induced Protein 10 (IP-10) Levels Week 2	2956.68 pg/mL Standard Deviation 1122.8	3809.83 pg/mL Standard Deviation 1442.4

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels Week 1	29.0477 pg/mL Standard Deviation 26.449	123.60 pg/mL Standard Deviation 26.8550
Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels Week 2	43.0115 pg/mL Standard Deviation 48.356	57.5810 pg/mL Standard Deviation 60.045

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Monocyte Chemoattractant Protein-1 (MCP-1) Levels Week 1	122.63 pg/mL Standard Deviation 28.2616	124.80 pg/mL Standard Deviation 27.9714
Monocyte Chemoattractant Protein-1 (MCP-1) Levels Week 2	255.30 pg/mL Standard Deviation 46.5051	187.12 pg/mL Standard Deviation 61.2899

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Granulocyte Colony-stimulating Factor (G-CSF) Levels Week 1	8.1585 pg/mL Standard Deviation 42.8679	157.86 pg/mL Standard Deviation 43.5125
Granulocyte Colony-stimulating Factor (G-CSF) Levels Week 2	8.6447 pg/mL Standard Deviation 78.3263	39.7275 pg/mL Standard Deviation 97.289

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.

Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=20 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Tumor Necrosis Factor (TNF)-Alpha Levels Week 1	1.3291 pg/mL Standard Deviation 21.8406	81.0170 pg/mL Standard Deviation 22.236
Tumor Necrosis Factor (TNF)-Alpha Levels Week 2	2.6108 pg/mL Standard Deviation 40.1411	17.0332 pg/mL Standard Deviation 49.723

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.

Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.

Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.

Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1, Week 2

Population: Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.

Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 4

Population: Due to budget limitations other laboratory experiments were prioritized and Immunoglobulin G (IgG) antibodies were not measured.

Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Day 60

Overall survival is defined as days from randomization to death and censored at last follow up.

Outcome measures

Measure	Duvelisib n=25 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 Participants Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Number of Participants Surviving	25 Participants	21 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1, Week 2

Population: Due to budget limitations other laboratory experiments were prioritized and VIP (an exploratory outcome) was not analyzed.

VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.

Outcome measures

Outcome data not reported

Adverse Events

Duvelisib

Serious events: 6 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Measure	Duvelisib n=25 participants at risk Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 participants at risk Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
General disorders Transfer to ICU and/or initiation of mechanical ventilation	12.0% 3/25 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.	9.1% 2/22 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.
General disorders Post-discharge hospitalization	12.0% 3/25 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.	0.00% 0/22 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.

Other adverse events

Measure	Duvelisib n=25 participants at risk Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.	Placebo n=22 participants at risk Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
Hepatobiliary disorders High alanine transaminase (ALT) - grade 2	0.00% 0/25 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.	4.5% 1/22 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.
Blood and lymphatic system disorders Leukopenia - grade 2	4.0% 1/25 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.	0.00% 0/22 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.
Blood and lymphatic system disorders Lymphopenia - grade 2 or 3	20.0% 5/25 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.	18.2% 4/22 • Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60. Adverse events that began or worsened after informed consent to participate was given were recorded.

Additional Information

Edmund Waller, MD, PhD

Emory University

Phone: 404-727-4995

Email: ewaller@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place