Trial Outcomes & Findings for Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients (NCT NCT04920916)

NCT ID: NCT04920916

Last Updated: 2023-11-03

Results Overview

Proportion of patients alive and free of invasive mechanical ventilation

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: at 28 Days ± 2d
• Results posted on: 2023-11-03

Participant Flow

Participant milestones

Measure	Dupilimab Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Phase IIa 60 Day Study STARTED	19	21
Phase IIa 60 Day Study COMPLETED	17	16
Phase IIa 60 Day Study NOT COMPLETED	2	5
1 Year Follow up (Phone Call) STARTED	17	16
1 Year Follow up (Phone Call) COMPLETED	16	13
1 Year Follow up (Phone Call) NOT COMPLETED	1	3
1 Year Follow up Visits STARTED	16	13
1 Year Follow up Visits COMPLETED	10	6
1 Year Follow up Visits NOT COMPLETED	6	7

Reasons for withdrawal

Measure	Dupilimab Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Phase IIa 60 Day Study Death	2	5
1 Year Follow up (Phone Call) Death	1	3
1 Year Follow up Visits Lost to Follow-up	6	7

Baseline Characteristics

Safety and Efficacy of Dupilumab for Treatment of Hospitalized COVID-19 Patients

Baseline characteristics by cohort

Measure	Dupilimab n=19 Participants Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.	Total n=40 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	63 years n=7 Participants	61.5 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	16 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=7 Participants	1 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	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	14 Participants n=7 Participants	27 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	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	21 participants n=7 Participants	40 participants n=5 Participants
Body Mass Index	33.6 kg/m^2 n=5 Participants	32.3 kg/m^2 n=7 Participants	33 kg/m^2 n=5 Participants

PRIMARY outcome

Timeframe: at 28 Days ± 2d

Proportion of patients alive and free of invasive mechanical ventilation

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Day 28 Ventilator Free Survival	0.79 proportion of participants	0.86 proportion of participants

PRIMARY outcome

Timeframe: 365 ± 90 days

Proportion of patients with abnormal diffusing capacity for carbon monoxide (DLCO) and/or 6 minute walk testing 1 year after acute COVID-19 infection.

Outcome measures

Measure	Dupilimab n=10 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=6 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow up Study 1 Year Outcome: Pulmonary Function Testing- Oxygen Diffusion and 6 Minute Walk Testing	0.30 proportion of participants	1.0 proportion of participants

SECONDARY outcome

Timeframe: Day 0 through Day 60

defined as an absolute eosinophil count > 0.6 k/µl at ≥ 1 measurement throughout the study period

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Proportion of Patients With Eosinophilia	0.26 proportion of participants	0.048 proportion of participants

SECONDARY outcome

Timeframe: Day 0 through Day 60

defined as number of new events divided by the total number of individuals in the population at risk for the time interval

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Cumulative Incidence of Grade 3 and 4 Clinical Adverse Events, Serious Adverse Events (SAEs) or Death	58 percent of participants	29 percent of participants

SECONDARY outcome

Timeframe: Day 0

Population: Five and four samples from the placebo and dupilumab groups, respectively, were unable to undergo sequencing.

Prevalence of delta variant in study population.

Outcome measures

Measure	Dupilimab n=15 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=16 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
SARS-CoV-2 Variants	100 percentage of participants	94 percentage of participants

SECONDARY outcome

Timeframe: Day 0 and Day 14

Population: Two subjects in the both the dupilumab and placebo groups were unable to undergo day 14 IgE assessment.

Change in levels (difference between day 14- day 0 levels).

Outcome measures

Measure	Dupilimab n=17 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=19 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Change in Plasma Total Immunoglobulin E (IgE) Levels	17.5 U/mL Interval 6.1 to 53.8	16.3 U/mL Interval 2.6 to 81.0

SECONDARY outcome

Timeframe: Day 0 through Day 14

Population: One and two patients in the placebo and dupilumab groups, respectively, were unable to undergo day 14 CRP assessment.

Change in levels (difference between day 14- day 0 levels)

Outcome measures

Measure	Dupilimab n=17 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=20 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Change in C-reactive Protein (CRP)	5.5 mg/dL Interval 2.3 to 14.3	8.9 mg/dL Interval 4.95 to 10.1

SECONDARY outcome

Timeframe: Day 0 through Day 14

Population: One and two patients in the placebo and dupilumab groups, respectively, were unable to undergo day 14 ferritin level assessment.

Change in levels (difference between day 14- day 0 levels).

Outcome measures

Measure	Dupilimab n=17 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=20 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Change in Ferritin	384 ng/mL Interval 131.0 to 595.0	545 ng/mL Interval 10.5 to 1115.5

SECONDARY outcome

Timeframe: Day 0 through Day 30

Measured in days

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Duration of Hospitalization	6 days Interval 4.0 to 22.0	6 days Interval 5.0 to 18.0

SECONDARY outcome

Timeframe: Day 60

All cause mortality by day 60

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Day 60 All Cause Mortality	11 percentage of participants	24 percentage of participants

SECONDARY outcome

Timeframe: at Day 28

Mortality rate

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Day 28 All-cause Mortality Rate	5 percentage of participants	14 percentage of participants

SECONDARY outcome

Timeframe: Day 60

Proportion of patients alive and free of invasive mechanical ventilation

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Day 60 Ventilator Free Survival	0.90 proportion of participants	0.76 proportion of participants

SECONDARY outcome

Timeframe: Day 0 through Day 60

Percentage

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Percentage of Patients Needing Extracorporeal Membrane Oxygenation (ECMO)	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Day 0 through Day 60

Percentage

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Percentage of Patients Needing Renal Replacement Therapy	11 percentage of participants	10 percentage of participants

SECONDARY outcome

Timeframe: Day 0 through Day 60

Percentage

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Percentage of Patients Needing Vasopressors	21 percentage of participants	19 percentage of participants

SECONDARY outcome

Timeframe: 365 days

Percent of subjects who died by 1 year.

Outcome measures

Measure	Dupilimab n=19 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow Up Study 1 Year Outcome: All-cause Mortality at 1 Year	16 percentage of participants	38 percentage of participants

SECONDARY outcome

Timeframe: 365 ± 90 days

Compare Enrollment HRCT to 1 year HRCT. Percent of abnormal on CT. Reported as percent of subjects with any abnormality on CT.

Outcome measures

Measure	Dupilimab n=10 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=6 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow-up Study 1 Year Outcome: Differences in High Resolution Computed Tomography (HRCT) Chest Scan Appearance Post Recovery	80 Percentage of participants	67 Percentage of participants

SECONDARY outcome

Timeframe: 365 ± 90 days

Proportion of patients with greater than 3% oxygen desaturation during 6 minute walk testing

Outcome measures

Measure	Dupilimab n=10 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=6 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow-up Study 1 Year Outcome: Conduct a 6 Minute Walk Testing	0.10 Proportion of participants	0.50 Proportion of participants

SECONDARY outcome

Timeframe: 365 ± 90 days

Percentage of subjects with a percent of predicted (compared to Global Lung Function Initiative (GLI) predicted values based on age, sex, height and ethnicity) below normal for forced expiratory volume (FEV1) or forced vital capacity (FVC), which are measures used to determine the volume of air that can be exhaled in one breath.

Outcome measures

Measure	Dupilimab n=10 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=6 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow up Study 1 Year Outcome: Pulmonary Function Testing- Abnormal Spirometry	30 percentage of participants	67 percentage of participants

SECONDARY outcome

Timeframe: 365 ± 90 days

Determine the proportion of patients with reduce neurocognitive function. Neurocognitive testing included completion of Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, PROMIS Depression, the Montreal Cognitive Assessment (MOCA), the Insomnia Severity Index (ISI), the Katz Index of Independence In Activities of Daily Living (Katz-ADL), EuroQOL (EQ)-5D-5L and Neuro- Quality of Life (QoL) questionnaires. Reduced neurocognitive function was determined if scoring from at least one of these tests was deemed a variation from population norm per scoring instructions.

Outcome measures

Measure	Dupilimab n=10 Participants Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=6 Participants Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Follow-up Study 1 Year Outcome: Assess Neurocognitive Function Using the MOCA	0.90 proportion of participants	0.83 proportion of participants

Adverse Events

Dupilimab

Serious events: 11 serious events

Other events: 0 other events

Deaths: 3 deaths

Placebo

Serious events: 6 serious events

Other events: 0 other events

Deaths: 8 deaths

Serious adverse events

Measure	Dupilimab n=19 participants at risk Active Dupilimab: 600 mg, given as two 300 mg subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28. Dupilumab: Participants will receive a loading dose of dupilumab (600 mg, given as two 300 mg subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (300 mg) will be given on days 14 and 28.	Placebo n=21 participants at risk Dupilimab Placebo: placebo (normal saline) will be given as two one mL subcutaneous injections on day 0/1. If participants are still hospitalized a second and third dose (1 mL) will be given on days 14 and 28. Placebo: Participants will receive a loading dose of normal saline (2 ml, given as two one ml subcutaneous injections) on day 0/1. If participants are still hospitalized a second and third dose (1 ml) will be given on days 14 and 28.
Injury, poisoning and procedural complications Injection Site Reactions	0.00% 0/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	0.00% 0/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Eye disorders Conjunctivitis	0.00% 0/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	9.5% 2/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Respiratory, thoracic and mediastinal disorders Bacterial pneumonia	10.5% 2/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	4.8% 1/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Infections and infestations Herpes viral infection	0.00% 0/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	0.00% 0/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Blood and lymphatic system disorders Eosinophilia	26.3% 5/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	4.8% 1/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Immune system disorders Hypereosinophilic syndrome	0.00% 0/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	0.00% 0/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.
Infections and infestations Other infections	21.1% 4/19 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.	9.5% 2/21 • Adverse events were collected on study day 0, 2, 5, 7, 14, 28 and 60 in initial Phase IIa study. Day 7, 28 and 60 were considered optional, although recommended, if patient discharged within the time frame. No SAEs/AEs were collected past day 60. Therefore, while all cause mortality was assessed up to 1 year, other AEs/SAEs were assessed up to day 60. All cause mortality was assessed up to 1 year. Other AEs/SAEs were assessed only up until day 60.

Other adverse events

Adverse event data not reported

Additional Information

William Petri

University of Virginia Health System

Phone: 434-305-9633

Email: wap3g@virginia.edu

Results disclosure agreements

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