Trial Outcomes & Findings for Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (NCT NCT04335136)
NCT ID: NCT04335136
Last Updated: 2021-08-02
Results Overview
The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
COMPLETED
PHASE2
185 participants
28 days
2021-08-02
Participant Flow
185 Patients were screened of whom 181 patients were randomized.
Participant milestones
| Measure |
Group A (Active) APN01
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Overall Study
STARTED
|
91
|
90
|
|
Overall Study
Treated
|
88
|
90
|
|
Overall Study
COMPLETED
|
77
|
83
|
|
Overall Study
NOT COMPLETED
|
14
|
7
|
Reasons for withdrawal
| Measure |
Group A (Active) APN01
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Overall Study
Death
|
8
|
4
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Health-threatening condition
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Erroneously randomized
|
2
|
0
|
Baseline Characteristics
Data of 1 patient in the placebo group are missing.
Baseline characteristics by cohort
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
Total
n=178 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.6 years
STANDARD_DEVIATION 11.3 • n=88 Participants
|
58.5 years
STANDARD_DEVIATION 12.4 • n=90 Participants
|
59.0 years
STANDARD_DEVIATION 11.9 • n=178 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=88 Participants
|
31 Participants
n=90 Participants
|
64 Participants
n=178 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=88 Participants
|
59 Participants
n=90 Participants
|
114 Participants
n=178 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=88 Participants
|
0 Participants
n=90 Participants
|
0 Participants
n=178 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
88 Participants
n=88 Participants
|
90 Participants
n=90 Participants
|
178 Participants
n=178 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=88 Participants
|
0 Participants
n=90 Participants
|
0 Participants
n=178 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
1 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
2 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
1 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
White
|
86 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
88 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
174 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=88 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=89 Participants • Data of 1 patient in the placebo group are missing.
|
0 Participants
n=177 Participants • Data of 1 patient in the placebo group are missing.
|
|
Region of Enrollment
Austria
|
19 participants
n=88 Participants
|
20 participants
n=90 Participants
|
39 participants
n=178 Participants
|
|
Region of Enrollment
Germany
|
2 participants
n=88 Participants
|
3 participants
n=90 Participants
|
5 participants
n=178 Participants
|
|
Region of Enrollment
Russia
|
67 participants
n=88 Participants
|
67 participants
n=90 Participants
|
134 participants
n=178 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: All randomized patients who had received at least 1 dose of investigational medicinal product (IMP).
The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
All Cause-death or Invasive Mechanical Ventilation
|
9 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Day 5Population: All randomized patients who had received at least 1 dose of IMP and had an LDH measurement at Day 5.
Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).
Outcome measures
| Measure |
Group A (Active) APN01
n=74 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=74 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Lactate Dehydrogenase (LDH) Level
|
5.82 Log U/L
Standard Deviation 0.470
|
5.80 Log U/L
Standard Deviation 0.433
|
SECONDARY outcome
Timeframe: 28 daysPopulation: All randomized patients who had received at least 1 dose of IMP.
28-day mortality (all cause-death).
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Mortality
|
9 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 28 daysPopulation: All randomized patients who had received at least 1 dose of IMP. In addition, a subgroup analysis was performed including only patients who were still alive at Day 28 (or discharged from the hospital/early terminated).
VFD up to 28 days or hospital discharge. VFD and mechanical-VFD (mVFD) were calculated as time in the study minus duration of ventilation and were set to zero if the duration of ventilation exceeded the time in the study. Three analysis approaches were used: 1) Death not censored: (m)VFD was set to zero for patients who died. 2) Death censored: patients who died before or on Day 28 were censored at the day before death. 3) Alive patients analyzed: only patients who were alive at Day 28, hospital discharge, or early termination were included in the analysis.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Ventilator-free Days (VFD)
VFD (death not censored)
|
17.2 days
Standard Deviation 8.8
|
16.7 days
Standard Deviation 8.4
|
|
Ventilator-free Days (VFD)
VFD (death censored)
|
17.4 days
Standard Deviation 8.6
|
16.7 days
Standard Deviation 8.4
|
|
Ventilator-free Days (VFD)
VFD (subgroup: alive patients)
|
18.9 days
Standard Deviation 7.3
|
17.9 days
Standard Deviation 7.4
|
|
Ventilator-free Days (VFD)
mVFD (death not censored)
|
25.7 days
Standard Deviation 8.4
|
25.1 days
Standard Deviation 8.7
|
|
Ventilator-free Days (VFD)
mVFD (death censored)
|
26.3 days
Standard Deviation 6.6
|
25.6 days
Standard Deviation 7.6
|
|
Ventilator-free Days (VFD)
mVFD (subgroup: alive patients)
|
28.2 days
Standard Deviation 1.9
|
26.9 days
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: 28 daysPopulation: All randomized patients who had received at least 1 dose of IMP.
Time to death (all causes).
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Time to Death
|
NA days
Interval 6.0 to 22.0
Median time to death could not be estimated due to an insufficient number of patients with events.
|
NA days
Interval 2.0 to 28.0
Median time to death could not be estimated due to an insufficient number of patients with events.
|
SECONDARY outcome
Timeframe: Day 7, Day 10, Day 14, Day 28Population: All randomized patients who had received at least 1 dose of IMP and who had a measurement of the WHO 11-Point Score System at the respective timepoint.
The WHO Clinical Progression Scale provides a measure of illness severity across an 11 point range from 0 (not infected) to 10 (dead) as follows (scores 4-9 contain measures of respiratory failure): Uninfected, no viral deoxyribonucleic acid (DNA) detected = 0; Asymptomatic, viral DNA detected = 1; Symptomatic, independent = 2; Symptomatic, assistance needed = 3; Hospitalized, no oxygen therapy = 4; Hospitalized, oxygen by mask or nasal prongs = 5; Hospitalized, oxygen by non-invasive ventilation (NIV) or high flow = 6; Intubation and mechanical ventilation, partial pressure of oxygen (pO2)/fraction of inspired oxygen (FiO2)≥ 150 or oxygen saturation (SpO2)/FiO2≥200 = 7; Mechanical ventilation, pO2/FiO2 \< 150 (SpO2/FiO2 \< 200) or vasopressors = 8; Mechanical ventilation, pO2/FiO2 \< 150 and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) = 9; Dead = 10. A decrease in the score reflects an improvement.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Day 7
|
2 Participants
|
0 Participants
|
|
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Day 10
|
17 Participants
|
13 Participants
|
|
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Day 14
|
38 Participants
|
32 Participants
|
|
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Day 28
|
72 Participants
|
74 Participants
|
SECONDARY outcome
Timeframe: Up to 28 daysPopulation: All patients who had received at least 1 dose of IMP.
The number of days from randomization to discharge from hospital was calculated (Kaplan-Meier analysis). Patients without hospitalization or without documented hospital discharge who completed the study or were early terminated before Day 28 were censored at the date of study completion or discontinuation, respectively. Patients who died before Day 28 were censored at the date of death even if early terminated before.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Time to Hospital Discharge
|
14 days
Interval 12.0 to 15.0
|
14 days
Interval 13.0 to 15.0
|
SECONDARY outcome
Timeframe: Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS)Population: All randomized patients who had received at least 1 dose of IMP and who had a measurement of viral RNA at the respective timepoint.
Viral RNA was assessed in blood samples using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and projected to RNA copies per mL.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Viral Ribonucleic Acid (RNA).
Day 1
|
27996 copies/mL
Standard Deviation 78877
|
3900 copies/mL
Standard Deviation 5848
|
|
Viral Ribonucleic Acid (RNA).
Day 3
|
20931 copies/mL
Standard Deviation 53182
|
13681 copies/mL
Standard Deviation 45287
|
|
Viral Ribonucleic Acid (RNA).
Day 5
|
9825 copies/mL
Standard Deviation 32979
|
11912 copies/mL
Standard Deviation 75457
|
|
Viral Ribonucleic Acid (RNA).
Day 7
|
5229 copies/mL
Standard Deviation 24514
|
2094 copies/mL
Standard Deviation 8742
|
|
Viral Ribonucleic Acid (RNA).
Day 14
|
9274 copies/mL
Standard Deviation 78304
|
53 copies/mL
Standard Deviation 455
|
|
Viral Ribonucleic Acid (RNA).
Day 28/EOS
|
36 copies/mL
Standard Deviation 217
|
—
|
SECONDARY outcome
Timeframe: Up to 28 days.Population: All randomized patients who had received at least 1 dose of IMP.
The time from randomization to an at least 2-point decrease in the WHO scale was calculated. The WHO Clinical Progression Scale provides a measure of illness severity across an 11 point range from 0 (not infected) to 10 (dead) as follows (scores 4-9 contain measures of respiratory failure): Uninfected, no viral DNA detected = 0; Asymptomatic, viral DNA detected = 1; Symptomatic, independent = 2; Symptomatic, assistance needed = 3; Hospitalized, no oxygen therapy = 4; Hospitalized, oxygen by mask or nasal prongs = 5; Hospitalized, oxygen by non-invasive ventilation (NIV) or high flow = 6; Intubation and mechanical ventilation, pO2/FiO2 ≥ 150 or SpO2/FiO2≥200 = 7; Mechanical ventilation, pO2/FiO2 \< 150 (SpO2/FiO2 \< 200) or vasopressors = 8; Mechanical ventilation, pO2/FiO2 \< 150 and vasopressors, dialysis, or ECMO = 9; Dead = 10. A decrease in the score reflects an improvement in disease status.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Time to a 2-point Decrease in WHO's 11-Point Score System
|
27 days
Interval 14.0 to 27.0
|
27 days
Interval 17.0 to 27.0
|
SECONDARY outcome
Timeframe: Up to 28 daysPopulation: All randomized patients who had received at least 1 dose of IMP.
The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Mechanical ventilation
|
7 Participants
|
7 Participants
|
|
Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Mechanical ventilation and oxygen supplementation
|
86 Participants
|
88 Participants
|
SECONDARY outcome
Timeframe: Up to 28 daysPopulation: All randomized patients who had received at least 1 dose of IMP.
Time from randomization to first use of invasive mechanical ventilation was calculated (Kaplan-Meier analysis). Patients without documented invasive mechanical ventilation who completed the study, were early terminated or discharged from hospital before Day 28 were censored at the date of study completion, discontinuation or discharge from hospital, respectively.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Time to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
|
NA days
Interval 0.0 to 14.0
Median time to first invasive mechanical ventilation could not be estimated due to an insufficient number of patients with events.
|
NA days
Interval 0.0 to 20.0
Median time to first invasive mechanical ventilation could not be estimated due to an insufficient number of patients with events.
|
SECONDARY outcome
Timeframe: Day 1, Day 7, Day 10, Day 14, and Day 28Population: All randomized patients who had received at least 1 dose of IMP and who had a measurement of PaO2/FiO2 at the respective timepoint.
The ratio in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) was assessed by analysis of patient's blood gas.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
PaO2/FiO2 Value
Day 10
|
290.00 mmHg
Standard Deviation 204.70
|
186.62 mmHg
Standard Deviation 87.83
|
|
PaO2/FiO2 Value
Day 14
|
197.00 mmHg
Standard Deviation 99.42
|
185.00 mmHg
Standard Deviation 67.20
|
|
PaO2/FiO2 Value
Day 1
|
223.07 mmHg
Standard Deviation 99.70
|
185.14 mmHg
Standard Deviation 79.79
|
|
PaO2/FiO2 Value
Day 7
|
218.74 mmHg
Standard Deviation 91.66
|
192.21 mmHg
Standard Deviation 92.71
|
|
PaO2/FiO2 Value
Day 28
|
261.00 mmHg
Standard Deviation NA
Data of only 1 patient were available.
|
185.00 mmHg
Standard Deviation 116.73
|
SECONDARY outcome
Timeframe: Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of studyPopulation: All randomized patients who had received at least 1 dose of IMP and who had a measurement of the mSOFA score at the respective timepoint.
The mSOFA score predicts intensive care unit mortality using clinical and laboratory variables. 5 organ systems (respiratory SpO2/FiO2; liver; cardiovascular/hypotension; Central nervous System/Glasgow Coma Score; renal/creatinine), all, except for liver, scored on a 0 to 4 scale (liver: 2-point scale: 0 or 3) according to specified criteria indicating severity, with the total score ranging from 0 to a maximum score of 19. A higher score reflects a worse disease state.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Day -1
|
2.6 score on a scale
Standard Error 1.2
|
2.2 score on a scale
Standard Error 1.4
|
|
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Day 7
|
1.8 score on a scale
Standard Error 2.5
|
1.6 score on a scale
Standard Error 2.1
|
|
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Day 10
|
1.0 score on a scale
Standard Error 1.7
|
1.0 score on a scale
Standard Error 1.6
|
|
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Day 14
|
1.0 score on a scale
Standard Error 2.4
|
0.9 score on a scale
Standard Error 1.7
|
|
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Day 28/EOS
|
0.2 score on a scale
Standard Error 0.6
|
0.8 score on a scale
Standard Error 1.8
|
SECONDARY outcome
Timeframe: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of studyPopulation: All randomized patients who had received at least 1 dose of IMP and who had a measurement of lymphocyte count at the respective timepoint.
Lymphocytes were assessed in blood samples from the patients.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Lymphocyte Count
Day -1
|
1.13 10^9 cells/L
Standard Deviation 0.694
|
1.06 10^9 cells/L
Standard Deviation 0.629
|
|
Lymphocyte Count
Day 3
|
1.25 10^9 cells/L
Standard Deviation 0.843
|
1.16 10^9 cells/L
Standard Deviation 0.662
|
|
Lymphocyte Count
Day 7
|
1.45 10^9 cells/L
Standard Deviation 0.948
|
1.62 10^9 cells/L
Standard Deviation 0.940
|
|
Lymphocyte Count
Day 10
|
1.74 10^9 cells/L
Standard Deviation 1.444
|
1.79 10^9 cells/L
Standard Deviation 0.782
|
|
Lymphocyte Count
Day 14
|
1.70 10^9 cells/L
Standard Deviation 0.773
|
1.71 10^9 cells/L
Standard Deviation 0.730
|
|
Lymphocyte Count
Day 28/EOS
|
2.28 10^9 cells/L
Standard Deviation 3.420
|
1.72 10^9 cells/L
Standard Deviation 0.559
|
SECONDARY outcome
Timeframe: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of studyPopulation: All randomized patients who had received at least 1 dose of IMP and who had a C-reactive protein measurement at the respective timepoint.
C-reactive protein was assessed in blood samples from the patients.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
C-reactive Protein Levels
Day 14
|
15.8 mg/L
Standard Deviation 29.66
|
38.3 mg/L
Standard Deviation 133.24
|
|
C-reactive Protein Levels
Day -1
|
56.0 mg/L
Standard Deviation 64.53
|
62.8 mg/L
Standard Deviation 51.75
|
|
C-reactive Protein Levels
Day 3
|
36.1 mg/L
Standard Deviation 53.75
|
43.7 mg/L
Standard Deviation 45.13
|
|
C-reactive Protein Levels
Day 7
|
21.7 mg/L
Standard Deviation 41.58
|
26.1 mg/L
Standard Deviation 38.71
|
|
C-reactive Protein Levels
Day 10
|
13.9 mg/L
Standard Deviation 24.24
|
26.3 mg/L
Standard Deviation 48.75
|
|
C-reactive Protein Levels
Day 28/EOS
|
4.9 mg/L
Standard Deviation 5.69
|
8.5 mg/L
Standard Deviation 11.54
|
SECONDARY outcome
Timeframe: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of studyPopulation: All randomized patients who had received at least 1 dose of IMP and who had a D-Dimer measurement at the respective timepoint.
D-Dimer was assessed in blood samples from the patients.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
D-Dimer
Day -1
|
1341 µg/L
Standard Deviation 2757
|
1187 µg/L
Standard Deviation 3994
|
|
D-Dimer
Day 3
|
1109 µg/L
Standard Deviation 1316
|
881 µg/L
Standard Deviation 959
|
|
D-Dimer
Day 7
|
1208 µg/L
Standard Deviation 1485
|
1139 µg/L
Standard Deviation 1590
|
|
D-Dimer
Day 10
|
988 µg/L
Standard Deviation 1135
|
1219 µg/L
Standard Deviation 2228
|
|
D-Dimer
Day 14
|
1015 µg/L
Standard Deviation 1520
|
1013 µg/L
Standard Deviation 2243
|
|
D-Dimer
Day 28/EOS
|
573 µg/L
Standard Deviation 629
|
685 µg/L
Standard Deviation 939
|
SECONDARY outcome
Timeframe: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of studyPopulation: All randomized patients who had received at least 1 dose of IMP and who had an LDH measurement at the respective timepoints.
Log transformed levels of LDH in blood were assessed as a surrogate marker for organ damage.
Outcome measures
| Measure |
Group A (Active) APN01
n=88 Participants
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 Participants
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Log-transformed Levels of LDH
Day -1
|
5.91 Log U/L
Standard Error 0.442
|
5.87 Log U/L
Standard Error 0.489
|
|
Log-transformed Levels of LDH
Day 3
|
5.86 Log U/L
Standard Error 0.440
|
5.88 Log U/L
Standard Error 0.422
|
|
Log-transformed Levels of LDH
Day 7
|
5.77 Log U/L
Standard Error 0.459
|
5.75 Log U/L
Standard Error 0.387
|
|
Log-transformed Levels of LDH
Day 10
|
5.66 Log U/L
Standard Error 0.464
|
5.67 Log U/L
Standard Error 0.401
|
|
Log-transformed Levels of LDH
Day 14
|
5.55 Log U/L
Standard Error 0.467
|
5.52 Log U/L
Standard Error 0.406
|
|
Log-transformed Levels of LDH
Day 28/EOS
|
5.43 Log U/L
Standard Error 0.305
|
5.50 Log U/L
Standard Error 0.383
|
Adverse Events
Group A (Active) APN01
Group B (Placebo Control)
Serious adverse events
| Measure |
Group A (Active) APN01
n=88 participants at risk
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 participants at risk
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
General disorders
General physical health deterioration
|
1.1%
1/88 • Number of events 1 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Infections and infestations
Sepsis
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.00%
0/88 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/88 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.00%
0/88 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/88 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Renal and urinary disorders
Renal failure
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/88 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
6.8%
6/88 • Number of events 6 • 28 days
|
7.8%
7/90 • Number of events 7 • 28 days
|
|
Vascular disorders
Infarction
|
1.1%
1/88 • Number of events 1 • 28 days
|
1.1%
1/90 • Number of events 1 • 28 days
|
|
Vascular disorders
Thrombosis
|
1.1%
1/88 • Number of events 1 • 28 days
|
0.00%
0/90 • 28 days
|
Other adverse events
| Measure |
Group A (Active) APN01
n=88 participants at risk
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 \[rhACE2\]) intravenously twice daily (BID).
|
Group B (Placebo Control)
n=90 participants at risk
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
11.4%
10/88 • Number of events 10 • 28 days
|
12.2%
11/90 • Number of events 11 • 28 days
|
|
Investigations
Blood potassium increased
|
5.7%
5/88 • Number of events 5 • 28 days
|
4.4%
4/90 • Number of events 4 • 28 days
|
|
Investigations
Electrocardiogram QT prolonged
|
2.3%
2/88 • Number of events 2 • 28 days
|
6.7%
6/90 • Number of events 6 • 28 days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/88 • 28 days
|
5.6%
5/90 • Number of events 5 • 28 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place