ACTION ON COVID-19: A Study to Test Whether BI 764198 Helps Lung Health of People Hospitalised With COVID-19

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04604184
• Collaborator: (none)
• Enrollment: 133
• Locations: 25
• Arms: 2
• Actual Duration (Months): 6.9
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This study is open to adults with COVID-19 infection who are in hospital and receive oxygen. Participants need to be 50 years of age or older and need to be at risk of further worsening of their condition.

The purpose of the study is to find out whether a medicine called BI 764198 helps people with COVID-19 infection and breathing problems. BI 764198 may prevent cell death and swelling of the lung tissue and therefore help patients with COVID-19 infection.

Participants are put into 2 groups by chance. One group of participants gets BI 764198 capsules and the other group gets placebo capsules. The placebo capsules look exactly like the BI 764198 capsules but do not contain any medicine. Participants take 1 capsule per day.

Participants are in the study for about a month. At study end, doctors compare the 2 groups for the number of patients that are alive and do not need mechanical breathing support. During the study, the doctors collect information on any health problems of the participants.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: BI 764198; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: BI 764198 Efficacy and Safety in Prevention/Progression of ARDS and ARDS-related Complications Secondary to COVID-19 (ACTION ON COVID-19)
• Actual Study Start Date: Nov 3, 2020
• Actual Primary Completion Date: Mar 24, 2021
• Actual Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BI 764198 treatment group	Drug: BI 764198; BI 764198
Placebo Comparator: Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Alive and Free of Mechanical Ventilation [At Day 29]

   Percentage of patients alive and free of mechanical ventilation at Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).

Secondary Outcome Measures

1. Percentage of Patients Alive and Discharged Free of Oxygen Use [At Day 29]

   Percentage of patients alive and discharged free of oxygen use is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).

2. Percentage of Patients With Occurrence of Any Component of Composite: In-hospital Mortality or Intensive Care Unit (ICU) Admission or Mechanical Ventilation [At Day 29]

   Percentage of patients with occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation is presented. Efficacy endpoint meets when a patient has occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation at Day 29. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).

3. Time to Clinical Improvement of at Least 2 Points (From Randomisation) on the World Health Organization Clinical Progression Scale, Discharge From the Hospital, or Considered Fit for Discharge [Up to Day 29]

   Meets when improvement of at least 2 points on World Health Organization (WHO) Clinical Progression Scale (CPS), discharge from hospital, fit for discharge (score 0, 1, 2, 3 on CPS), whichever comes first. WHO CPS: 0. Uninfected; no viral RNA detected; 1. Asymptomatic; viral RNA detected; 2. Symptomatic; independent; 3. Symptomatic; assistance needed; 4. Hospitalised; no oxygen therapy; 5. Hospitalised; oxygen by mask or nasal prongs; 6. Hospitalised; oxygen by non-invasive ventilation or high flow; 7. Intubation + mechanical ventilation, partial pressure of oxygen/fraction of inspired oxygen (pO2/FiO2) ≥150 or oxygen saturation/FiO2 (SpO2/FiO2) ≥200; 8. Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors; 9. Mechanical ventilation pO2/FiO2 <150 + vasopressors, dialysis, extracorporeal membrane oxygenation (ECMO); 10. Death Only patients with event were analysed. One patient had no creatinine at baseline value, therefore excluded from statistical analysis (N=128).

4. Number of Ventilator Free Days [Up to Day 29]

   Number of ventilator free days by Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).

5. Percentage of Mortality at Day 15, 29, 60 and 90 [At Day 15, 29, 60 and 90]

   Percentage of mortality is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 50 years

• SARS-CoV-2 infection positive confirmed by PCR or approved point-of-care test

• A score of 5 (hospitalised; oxygen by mask or nasal prongs) or 6 (hospitalised; oxygen by non-invasive ventilation or high flow), but not previously ≥7, on the WHO Clinical Progression Scale.

• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

• Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must abstain from male female sex or must use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly during hospitalisation for at least 7 days after last trial drug intake

Exclusion Criteria:

• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × the upper limit of normal (ULN).

• Known active infection with HIV or hepatitis B or C.

• Pulmonary oedema/respiratory failure due to cardiogenic insult.

• Previous to hospitalisation, on long-term oxygen therapy.

• A confirmed baseline prolongation of QTc interval to greater than 450 ms in males or 470 ms in females according to the Bazett formula, or any other relevant ECG finding at screening, or concomitant use of medication prolonging QT interval.

• Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR <30 mL/min/1.73 m2).

History of the following cardiac conditions:

• Myocardial infarction within 3 months prior to the first dose

• Unstable angina

• History of clinically significant long QT features on electrocardiogram (ECG) or history of familial long QT

• Anticipated transfer/discharge to another hospital or care facility other than their place of residence

• Further exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Irvine	Orange	California	United States	92868
2	Rapides Regional Medical Center	Alexandria	Louisiana	United States	71301
3	St. Elizabeth's Medical Center	Boston	Massachusetts	United States	02135
4	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
5	Mercy Health St. Vincent Medical Center	Toledo	Ohio	United States	43608
6	Providence Regional Medical Center	Everett	Washington	United States	98201
7	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
8	Hospital Luxemburgo	Belo Horizonte		Brazil	32380-490
9	IPECC - Instituto de Pesquisa Clínica de Campinas	Campinas		Brazil	13060-080
10	Hospital Ernesto Dornelles	Porto Alegre		Brazil	90160-092
11	Hospital Regional Hans Dieter Schmidt	Santa Catarina		Brazil	89227
12	Hospital de Base - Fac Med de Sao Jose do Rio Preto	Sao Jose do Rio Preto		Brazil	15090-000
13	Hospital Padre Alberto Hurtado	Santiago		Chile	8880465
14	Hospital Carlos Van Buren	Valparaiso		Chile	2341131
15	Hospital Cardiologica Aguascalientes	Aguascalientes		Mexico	20230
16	Hospital General de Culiacán "Dr. Bernardo J. Gastellum"	Culiacán		Mexico	80230
17	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey		Mexico	64460
18	Hospital Auxilio Mutuo	Hato Rey		Puerto Rico	00919
19	Hospital Municipal de San Juan	Rio Piedras		Puerto Rico	00936
20	Hospital A Coruña	A Coruña		Spain	15006
21	Hospital General Universitario de Alicante	Alicante		Spain	03010
22	Hospital Universitario Infanta Leonor	Madrid		Spain	28031
23	Hospital Clínico San Carlos	Madrid		Spain	28040
24	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
25	Hospital Son Espases	Palma de Mallorca		Spain	07120

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 8, 2021
• Statistical Analysis Plan - Apr 8, 2021

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04604184
• Other Study ID Numbers: 1434-0009; 2020-003211-96
• First Posted: Oct 27, 2020
• Last Update Posted: Apr 11, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	This randomised, placebo-controlled, double-blind, proof-of-concept exploratory trial was to evaluate the efficacy and safety of BI 764198, an inhibitor of the transient receptor potential subtype C6 (TRPC6), compared to placebo in reducing risk or severity of acute respiratory distress syndrome (ARDS) in patients hospitalised for coronavirus disease appeared in 2019 (COVID-19).
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Period Title: Overall Study
STARTED	67	66
Treated	65	64
COMPLETED	47	47
NOT COMPLETED	20	19

Baseline Characteristics

Arm/Group Title	BI 764198 Treatment Group	Placebo	Total
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Total of all reporting groups
Overall Participants	65	64	129
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.8 (8.3)	63.6 (7.9)	63.7 (8.1)
Sex: Female, Male (Count of Participants)
Female	24 36.9%	25 39.1%	49 38%
Male	41 63.1%	39 60.9%	80 62%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	39 60%	35 54.7%	74 57.4%
Not Hispanic or Latino	26 40%	29 45.3%	55 42.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 7.7%	7 10.9%	12 9.3%
Asian	0 0%	3 4.7%	3 2.3%
Native Hawaiian or Other Pacific Islander	2 3.1%	0 0%	2 1.6%
Black or African American	3 4.6%	3 4.7%	6 4.7%
White	53 81.5%	47 73.4%	100 77.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 3.1%	4 6.3%	6 4.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Alive and Free of Mechanical Ventilation
Description	Percentage of patients alive and free of mechanical ventilation at Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).
Time Frame	At Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Number [Percentage of patients]	83.1	87.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3232
	Comments
	Method	Regression, Logistic
	Comments	includes treatment, age, severity grade and creatinine at baseline, duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-5.39
	Confidence Interval	(2-Sided) 95%; -16.08 to 5.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Patients Alive and Discharged Free of Oxygen Use
Description	Percentage of patients alive and discharged free of oxygen use is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).
Time Frame	At Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Number [Percentage of patients]	75.4	82.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1274
	Comments
	Method	Regression, Logistic
	Comments	includes treatment, age, severity grade and creatinine at baseline, duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-9.86
	Confidence Interval	(2-Sided) 95%; -22.54 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Patients With Occurrence of Any Component of Composite: In-hospital Mortality or Intensive Care Unit (ICU) Admission or Mechanical Ventilation
Description	Percentage of patients with occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation is presented. Efficacy endpoint meets when a patient has occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation at Day 29. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).
Time Frame	At Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Number [Percentage of patients]	26.2	23.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6828
	Comments
	Method	Regression, Logistic
	Comments	includes treatment, age, severity grade and creatinine at baseline, duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.66
	Confidence Interval	(2-Sided) 95%; -10.11 to 15.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Clinical Improvement of at Least 2 Points (From Randomisation) on the World Health Organization Clinical Progression Scale, Discharge From the Hospital, or Considered Fit for Discharge
Description	Meets when improvement of at least 2 points on World Health Organization (WHO) Clinical Progression Scale (CPS), discharge from hospital, fit for discharge (score 0, 1, 2, 3 on CPS), whichever comes first. WHO CPS: 0. Uninfected; no viral RNA detected; 1. Asymptomatic; viral RNA detected; 2. Symptomatic; independent; 3. Symptomatic; assistance needed; 4. Hospitalised; no oxygen therapy; 5. Hospitalised; oxygen by mask or nasal prongs; 6. Hospitalised; oxygen by non-invasive ventilation or high flow; 7. Intubation + mechanical ventilation, partial pressure of oxygen/fraction of inspired oxygen (pO2/FiO2) ≥150 or oxygen saturation/FiO2 (SpO2/FiO2) ≥200; 8. Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors; 9. Mechanical ventilation pO2/FiO2 <150 + vasopressors, dialysis, extracorporeal membrane oxygenation (ECMO); 10. Death Only patients with event were analysed. One patient had no creatinine at baseline value, therefore excluded from statistical analysis (N=128).
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Median (Inter-Quartile Range) [Days]	9	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0445
	Comments
	Method	Regression, Cox
	Comments	Covariates are treatment, age, severity grade and creatinine at baseline and duration of symptoms before hospitalization
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Ventilator Free Days
Description	Number of ventilator free days by Day 29 is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts. Only pts with non-missing results were included. Of all pts randomised, number of pts not treated was similar in BI 764198 (2/67 pts) and placebo group (2/66 pts). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Mean (Standard Deviation) [Days]	24.12 (8.81)	25.08 (7.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5526
	Comments
	Method	ANCOVA
	Comments	Fixed effects of treatment, age, severity grade and creatinine at baseline and duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -3.47 to 1.87
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.35
	Estimation Comments	Difference = covariate adjusted BI 764198 - covariate adjusted Placebo

6. Secondary Outcome

Title	Percentage of Mortality at Day 15, 29, 60 and 90
Description	Percentage of mortality is presented. One patient had no creatinine at baseline value and was therefore excluded from the statistical analysis (N=128).
Time Frame	At Day 15, 29, 60 and 90

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).

Arm/Group Title	BI 764198 Treatment Group	Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
Measure Participants	65	64
Day 15	6.2	1.6
Day 29	12.3	7.8
Day 60	15.4	7.8
Day 90	16.9	7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments	Day 15
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0995
	Comments
	Method	Regression, Logistic
	Comments	Includes treatment, age, severity grade and creatinine at baseline, and duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.32
	Confidence Interval	(2-Sided) 95%; -1.01 to 11.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments	Day 29
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1992
	Comments
	Method	Regression, Logistic
	Comments	Includes treatment, age, severity grade and creatinine at baseline, and duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.06
	Confidence Interval	(2-Sided) 95%; -3.19 to 15.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments	Day 60
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0709
	Comments
	Method	Regression, Logistic
	Comments	Includes treatment, age, severity grade and creatinine at baseline, and duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	8.93
	Confidence Interval	(2-Sided) 95%; -0.76 to 18.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	BI 764198 Treatment Group, Placebo
	Comments	Day 90
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0412
	Comments
	Method	Regression, Logistic
	Comments	Includes treatment, age, severity grade and creatinine at baseline, and duration of symptoms before hospitalisation as covariates
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	10.35
	Confidence Interval	(2-Sided) 95%; 0.41 to 20.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From first administration of the study drug to end of study, 90 days in total.
Adverse Event Reporting Description	Full Analysis Set (FAS): FAS included all patients (pts) in randomized set (RS) who received at least 1 dose of trial drug, comprised 129 pts (85.4%). Of all pts randomised, number (%) of pts not treated was similar in BI 764198 (2/67 pts [3.0%]) and placebo group (2/66 pts [3.0%]). The 4 pts excluded from FAS discontinued trial before receiving treatment for following reasons: pt's withdrawal (n=2), meeting an exclusion criterion (n=1), and clinical worsening (n=1).
Arm/Group Title	BI 764198 Treatment Group		Placebo
Arm/Group Description	Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received BI 764198, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.		Subjects who were hospitalised for infection with SARS-CoV-2, the virus that causes COVID-19 received Placebo, oral or, only if needed, per nasogastric intubation once per day starting on Day 1, with a treatment duration of up to 28 days.
All Cause Mortality
	BI 764198 Treatment Group		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/65 (16.9%)		5/64 (7.8%)
Serious Adverse Events
	BI 764198 Treatment Group		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/65 (29.2%)		17/64 (26.6%)
Blood and lymphatic system disorders
Anaemia	1/65 (1.5%)		0/64 (0%)
Cardiac disorders
Cardiac failure congestive	0/65 (0%)		2/64 (3.1%)
Cardiac tamponade	1/65 (1.5%)		0/64 (0%)
Cardiac ventricular thrombosis	0/65 (0%)		1/64 (1.6%)
Cardiogenic shock	1/65 (1.5%)		1/64 (1.6%)
Diastolic dysfunction	0/65 (0%)		1/64 (1.6%)
Ventricular tachycardia	0/65 (0%)		1/64 (1.6%)
Acute myocardial infarction	1/65 (1.5%)		0/64 (0%)
Atrial fibrillation	0/65 (0%)		1/64 (1.6%)
Bradycardia	0/65 (0%)		1/64 (1.6%)
Right ventricular dilatation	0/65 (0%)		1/64 (1.6%)
Right ventricular dysfunction	0/65 (0%)		1/64 (1.6%)
Endocrine disorders
Adrenal insufficiency	0/65 (0%)		1/64 (1.6%)
Gastrointestinal disorders
Diarrhoea	1/65 (1.5%)		0/64 (0%)
General disorders
Death	1/65 (1.5%)		0/64 (0%)
Multiple organ dysfunction syndrome	1/65 (1.5%)		0/64 (0%)
Hepatobiliary disorders
Hepatitis toxic	1/65 (1.5%)		0/64 (0%)
Liver injury	1/65 (1.5%)		0/64 (0%)
Infections and infestations
COVID-19	1/65 (1.5%)		2/64 (3.1%)
COVID-19 pneumonia	4/65 (6.2%)		2/64 (3.1%)
Lower respiratory tract infection	0/65 (0%)		1/64 (1.6%)
Septic shock	2/65 (3.1%)		3/64 (4.7%)
Aspergillus infection	1/65 (1.5%)		0/64 (0%)
Citrobacter infection	1/65 (1.5%)		0/64 (0%)
Lower respiratory tract infection bacterial	1/65 (1.5%)		0/64 (0%)
Pneumonia	2/65 (3.1%)		0/64 (0%)
Sepsis	1/65 (1.5%)		1/64 (1.6%)
Investigations
Electrocardiogram QT prolonged	0/65 (0%)		1/64 (1.6%)
Metabolism and nutrition disorders
Hyperkalaemia	0/65 (0%)		1/64 (1.6%)
Nervous system disorders
Encephalopathy	0/65 (0%)		1/64 (1.6%)
Ischaemic stroke	1/65 (1.5%)		0/64 (0%)
Toxic encephalopathy	2/65 (3.1%)		0/64 (0%)
Psychiatric disorders
Delirium	1/65 (1.5%)		1/64 (1.6%)
Renal and urinary disorders
Acute kidney injury	4/65 (6.2%)		5/64 (7.8%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/65 (3.1%)		3/64 (4.7%)
Acute respiratory failure	3/65 (4.6%)		2/64 (3.1%)
Dyspnoea	1/65 (1.5%)		0/64 (0%)
Haemothorax	1/65 (1.5%)		0/64 (0%)
Hypoxia	2/65 (3.1%)		0/64 (0%)
Pneumomediastinum	2/65 (3.1%)		1/64 (1.6%)
Pneumothorax	1/65 (1.5%)		2/64 (3.1%)
Pulmonary embolism	0/65 (0%)		1/64 (1.6%)
Respiratory distress	0/65 (0%)		1/64 (1.6%)
Respiratory failure	4/65 (6.2%)		5/64 (7.8%)
Pulmonary hypertension	1/65 (1.5%)		1/64 (1.6%)
Vascular disorders
Deep vein thrombosis	1/65 (1.5%)		1/64 (1.6%)
Distributive shock	1/65 (1.5%)		0/64 (0%)
Hypotension	0/65 (0%)		1/64 (1.6%)
Other (Not Including Serious) Adverse Events
	BI 764198 Treatment Group		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/65 (15.4%)		12/64 (18.8%)
Cardiac disorders
Tachycardia	0/65 (0%)		4/64 (6.3%)
Gastrointestinal disorders
Constipation	4/65 (6.2%)		6/64 (9.4%)
Investigations
Electrocardiogram QT prolonged	3/65 (4.6%)		4/64 (6.3%)
Metabolism and nutrition disorders
Hyperkalaemia	2/65 (3.1%)		6/64 (9.4%)
Vascular disorders
Hypotension	4/65 (6.2%)		5/64 (7.8%)

Limitations/Caveats

This trial was terminated early following the recommendation of a Data Monitoring Committee.

More Information

Certain Agreements

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

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.