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

Study Overview
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Brief Summary
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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.

Official Title
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BI 764198 Efficacy and Safety in Prevention/Progression of ARDS and ARDS-related Complications Secondary to COVID-19 (ACTION ON COVID-19)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: BI 764198
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 764198 treatment group<br> | Drug: BI 764198<br>* BI 764198<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Alive and Free of Mechanical Ventilation | 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). | At Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Alive and Discharged Free of Oxygen Use | 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). | 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 | 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). | At Day 29 | 
| 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 | 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). | Up to Day 29 | 
| Number of Ventilator Free Days | 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). | Up to Day 29 | 
| Percentage of Mortality 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). | At Day 15, 29, 60 and 90 |