COVID-19
Conditions
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.
Interventions
DRUGBI 764198
BI 764198
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
Countries
Brazil, Chile, Mexico, Puerto Rico, Spain, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| BI 764198 Treatment Group 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. | 65 |
| Placebo 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. | 64 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 5 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Due to sponsor decision | 9 | 7 |
| Overall Study | Not treated | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Transfer to healthcare | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | BI 764198 Treatment Group |
|---|---|---|---|
| Age, Continuous | 63.6 Years STANDARD_DEVIATION 7.9 | 63.7 Years STANDARD_DEVIATION 8.1 | 63.8 Years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 74 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 55 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 12 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) White | 47 Participants | 100 Participants | 53 Participants |
| Sex: Female, Male Female | 25 Participants | 49 Participants | 24 Participants |
| Sex: Female, Male Male | 39 Participants | 80 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 65 | 5 / 64 |
| other Total, other adverse events | 10 / 65 | 12 / 64 |
| serious Total, serious adverse events | 19 / 65 | 17 / 64 |
Outcome results
Primary
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).
Time frame: At Day 29
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| BI 764198 Treatment Group | Percentage of Patients Alive and Free of Mechanical Ventilation | 83.1 Percentage of patients |
| Placebo | Percentage of Patients Alive and Free of Mechanical Ventilation | 87.5 Percentage of patients |
p-value: 0.323295% CI: [-16.08, 5.3]Regression, Logistic
Secondary
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).
Time frame: Up to Day 29
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 764198 Treatment Group | Number of Ventilator Free Days | 24.12 Days | Standard Deviation 8.81 |
| Placebo | Number of Ventilator Free Days | 25.08 Days | Standard Deviation 7.85 |
p-value: 0.552695% CI: [-3.47, 1.87]ANCOVA
Secondary
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).
Time frame: At Day 15, 29, 60 and 90
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BI 764198 Treatment Group | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 15 | 6.2 Percentage of patients |
| BI 764198 Treatment Group | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 29 | 12.3 Percentage of patients |
| BI 764198 Treatment Group | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 60 | 15.4 Percentage of patients |
| BI 764198 Treatment Group | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 90 | 16.9 Percentage of patients |
| Placebo | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 90 | 7.8 Percentage of patients |
| Placebo | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 15 | 1.6 Percentage of patients |
| Placebo | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 60 | 7.8 Percentage of patients |
| Placebo | Percentage of Mortality at Day 15, 29, 60 and 90 | Day 29 | 7.8 Percentage of patients |
Comparison: Day 15p-value: 0.099595% CI: [-1.01, 11.65]Regression, Logistic
Comparison: Day 29p-value: 0.199295% CI: [-3.19, 15.31]Regression, Logistic
Comparison: Day 60p-value: 0.070995% CI: [-0.76, 18.62]Regression, Logistic
Comparison: Day 90p-value: 0.041295% CI: [0.41, 20.28]Regression, Logistic
Secondary
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).
Time frame: At Day 29
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| BI 764198 Treatment Group | Percentage of Patients Alive and Discharged Free of Oxygen Use | 75.4 Percentage of patients |
| Placebo | Percentage of Patients Alive and Discharged Free of Oxygen Use | 82.8 Percentage of patients |
p-value: 0.127495% CI: [-22.54, 2.82]Regression, Logistic
Secondary
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).
Time frame: At Day 29
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| BI 764198 Treatment Group | Percentage of Patients With Occurrence of Any Component of Composite: In-hospital Mortality or Intensive Care Unit (ICU) Admission or Mechanical Ventilation | 26.2 Percentage of patients |
| Placebo | Percentage of Patients With Occurrence of Any Component of Composite: In-hospital Mortality or Intensive Care Unit (ICU) Admission or Mechanical Ventilation | 23.4 Percentage of patients |
p-value: 0.682895% CI: [-10.11, 15.43]Regression, Logistic
Secondary
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).
Time frame: Up to Day 29
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| BI 764198 Treatment Group | 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 | 9 Days |
| Placebo | 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 | 7 Days |
p-value: 0.044595% CI: [0.46, 0.99]Regression, Cox