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Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19 (APN01-COVID-19)

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ClinicalTrials.gov Identifier: NCT04335136
Recruitment Status : Completed
First Posted : April 6, 2020
Results First Posted : August 2, 2021
Last Update Posted : August 2, 2021
Sponsor:
Information provided by (Responsible Party):
Apeiron Biologics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition COVID-19
Interventions Drug: RhACE2 APN01
Drug: Physiological saline solution
Enrollment 185
Recruitment Details 185 Patients were screened of whom 181 patients were randomized.
Pre-assignment Details  
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID). Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Period Title: Overall Study
Started [1] 91 90
Treated 88 90
Completed 77 83
Not Completed 14 7
Reason Not Completed
Death             8             4
Lost to Follow-up             2             0
Protocol Violation             1             0
Withdrawal by Subject             1             1
Health-threatening condition             0             1
Adverse Event             0             1
Erroneously randomized             2             0
[1]
Patients randomized.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control) Total
Hide Arm/Group Description Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID). Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID). Total of all reporting groups
Overall Number of Baseline Participants 88 90 178
Hide Baseline Analysis Population Description
All randomized patients who received at least 1 dose of investigational medicinal product (IMP).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 88 participants 90 participants 178 participants
59.6  (11.3) 58.5  (12.4) 59.0  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 90 participants 178 participants
Female
33
  37.5%
31
  34.4%
64
  36.0%
Male
55
  62.5%
59
  65.6%
114
  64.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 90 participants 178 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
88
 100.0%
90
 100.0%
178
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants 89 participants 177 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.1%
1
   1.1%
2
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.1%
0
   0.0%
1
   0.6%
White
86
  97.7%
88
  98.9%
174
  98.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Data of 1 patient in the placebo group are missing.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Austria Number Analyzed 88 participants 90 participants 178 participants
19 20 39
Germany Number Analyzed 88 participants 90 participants 178 participants
2 3 5
Russia Number Analyzed 88 participants 90 participants 178 participants
67 67 134
1.Primary Outcome
Title All Cause-death or Invasive Mechanical Ventilation
Hide Description The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of investigational medicinal product (IMP).
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Measure Type: Count of Participants
Unit of Measure: Participants
9
  10.2%
12
  13.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A (Active) APN01, Group B (Placebo Control)
Comments

Hypothesis tested: H0: pAPN01 = pPlacebo; H1: pAPN01 ≠ pPlacebo (with p=proportion of patients with event).

A total of 186 patients (93 per group) was estimated to yield 80% power to detect a 20% absolute risk reduction in the primary, from 50% in the placebo group to 30% in the APN01 group, at a 2-sided alpha of 0.05. To consider patients who would be randomized but not treated, a total of 200 patients (100 per group) were planned to be enrolled.

Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5207
Comments The level of significance was 5% (2-sided).
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group A (Active) APN01, Group B (Placebo Control)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3588
Comments [Not Specified]
Method Regression, Logistic
Comments Degree of freedom: 1
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.23 to 1.70
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Lactate Dehydrogenase (LDH) Level
Hide Description Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and had an LDH measurement at Day 5.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 74 74
Mean (Standard Deviation)
Unit of Measure: Log U/L
5.82  (0.470) 5.80  (0.433)
3.Secondary Outcome
Title Mortality
Hide Description 28-day mortality (all cause-death).
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Measure Type: Count of Participants
Unit of Measure: Participants
9
  10.2%
7
   7.8%
4.Secondary Outcome
Title Ventilator-free Days (VFD)
Hide Description

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.

Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: days
VFD (death not censored) Number Analyzed 88 participants 90 participants
17.2  (8.8) 16.7  (8.4)
VFD (death censored) Number Analyzed 88 participants 90 participants
17.4  (8.6) 16.7  (8.4)
VFD (subgroup: alive patients) Number Analyzed 80 participants 84 participants
18.9  (7.3) 17.9  (7.4)
mVFD (death not censored) Number Analyzed 88 participants 90 participants
25.7  (8.4) 25.1  (8.7)
mVFD (death censored) Number Analyzed 88 participants 90 participants
26.3  (6.6) 25.6  (7.6)
mVFD (subgroup: alive patients) Number Analyzed 79 participants 83 participants
28.2  (1.9) 26.9  (5.8)
5.Secondary Outcome
Title Time to Death
Hide Description Time to death (all causes).
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Median (Full Range)
Unit of Measure: days
NA [1] 
(6 to 22)
NA [1] 
(2 to 28)
[1]
Median time to death could not be estimated due to an insufficient number of patients with events.
6.Secondary Outcome
Title Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Hide Description

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.

Time Frame Day 7, Day 10, Day 14, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Measure Type: Count of Participants
Unit of Measure: Participants
Day 7 Number Analyzed 88 participants 88 participants
2
   2.3%
0
   0.0%
Day 10 Number Analyzed 86 participants 85 participants
17
  19.8%
13
  15.3%
Day 14 Number Analyzed 83 participants 85 participants
38
  45.8%
32
  37.6%
Day 28 Number Analyzed 79 participants 83 participants
72
  91.1%
74
  89.2%
7.Secondary Outcome
Title Time to Hospital Discharge
Hide Description

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.

Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Median (95% Confidence Interval)
Unit of Measure: days
14
(12 to 15)
14
(13 to 15)
8.Secondary Outcome
Title Viral Ribonucleic Acid (RNA).
Hide Description Viral RNA was assessed in blood samples using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and projected to RNA copies per mL.
Time Frame Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had a measurement of viral RNA at the respective timepoint.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: copies/mL
Day 1 Number Analyzed 59 participants 49 participants
27996  (78877) 3900  (5848)
Day 3 Number Analyzed 47 participants 58 participants
20931  (53182) 13681  (45287)
Day 5 Number Analyzed 56 participants 64 participants
9825  (32979) 11912  (75457)
Day 7 Number Analyzed 65 participants 61 participants
5229  (24514) 2094  (8742)
Day 14 Number Analyzed 73 participants 73 participants
9274  (78304) 53  (455)
Day 28/EOS Number Analyzed 37 participants 0 participants
36  (217)
9.Secondary Outcome
Title Time to a 2-point Decrease in WHO's 11-Point Score System
Hide Description

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.

Time Frame Up to 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Median (95% Confidence Interval)
Unit of Measure: days
27
(14 to 27)
27
(17 to 27)
10.Secondary Outcome
Title Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Hide Description The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Measure Type: Count of Participants
Unit of Measure: Participants
Mechanical ventilation
7
   8.0%
7
   7.8%
Mechanical ventilation and oxygen supplementation
86
  97.7%
88
  97.8%
11.Secondary Outcome
Title Time to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Hide Description

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.

Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Median (Full Range)
Unit of Measure: days
NA [1] 
(0 to 14)
NA [1] 
(0 to 20)
[1]
Median time to first invasive mechanical ventilation could not be estimated due to an insufficient number of patients with events.
12.Secondary Outcome
Title PaO2/FiO2 Value
Hide Description The ratio in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) was assessed by analysis of patient's blood gas.
Time Frame Day 1, Day 7, Day 10, Day 14, and Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had a measurement of PaO2/FiO2 at the respective timepoint.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: mmHg
Day 1 Number Analyzed 30 participants 28 participants
223.07  (99.70) 185.14  (79.79)
Day 7 Number Analyzed 19 participants 24 participants
218.74  (91.66) 192.21  (92.71)
Day 10 Number Analyzed 14 participants 13 participants
290.00  (204.70) 186.62  (87.83)
Day 14 Number Analyzed 9 participants 11 participants
197.00  (99.42) 185.00  (67.20)
Day 28 Number Analyzed 1 participants 3 participants
261.00 [1]   (NA) 185.00  (116.73)
[1]
Data of only 1 patient were available.
13.Secondary Outcome
Title Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Hide Description 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.
Time Frame Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of study
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Error)
Unit of Measure: score on a scale
Day -1 Number Analyzed 80 participants 80 participants
2.6  (1.2) 2.2  (1.4)
Day 7 Number Analyzed 83 participants 77 participants
1.8  (2.5) 1.6  (2.1)
Day 10 Number Analyzed 80 participants 77 participants
1.0  (1.7) 1.0  (1.6)
Day 14 Number Analyzed 79 participants 75 participants
1.0  (2.4) 0.9  (1.7)
Day 28/EOS Number Analyzed 39 participants 38 participants
0.2  (0.6) 0.8  (1.8)
14.Secondary Outcome
Title Lymphocyte Count
Hide Description Lymphocytes were assessed in blood samples from the patients.
Time Frame Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had a measurement of lymphocyte count at the respective timepoint.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: 10^9 cells/L
Day -1 Number Analyzed 82 participants 82 participants
1.13  (0.694) 1.06  (0.629)
Day 3 Number Analyzed 85 participants 83 participants
1.25  (0.843) 1.16  (0.662)
Day 7 Number Analyzed 82 participants 80 participants
1.45  (0.948) 1.62  (0.940)
Day 10 Number Analyzed 81 participants 75 participants
1.74  (1.444) 1.79  (0.782)
Day 14 Number Analyzed 77 participants 73 participants
1.70  (0.773) 1.71  (0.730)
Day 28/EOS Number Analyzed 37 participants 37 participants
2.28  (3.420) 1.72  (0.559)
15.Secondary Outcome
Title C-reactive Protein Levels
Hide Description C-reactive protein was assessed in blood samples from the patients.
Time Frame Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had a C-reactive protein measurement at the respective timepoint.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: mg/L
Day -1 Number Analyzed 77 participants 79 participants
56.0  (64.53) 62.8  (51.75)
Day 3 Number Analyzed 80 participants 74 participants
36.1  (53.75) 43.7  (45.13)
Day 7 Number Analyzed 78 participants 76 participants
21.7  (41.58) 26.1  (38.71)
Day 10 Number Analyzed 74 participants 71 participants
13.9  (24.24) 26.3  (48.75)
Day 14 Number Analyzed 69 participants 73 participants
15.8  (29.66) 38.3  (133.24)
Day 28/EOS Number Analyzed 36 participants 37 participants
4.9  (5.69) 8.5  (11.54)
16.Secondary Outcome
Title D-Dimer
Hide Description D-Dimer was assessed in blood samples from the patients.
Time Frame Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had a D-Dimer measurement at the respective timepoint.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Deviation)
Unit of Measure: µg/L
Day -1 Number Analyzed 71 participants 73 participants
1341  (2757) 1187  (3994)
Day 3 Number Analyzed 69 participants 74 participants
1109  (1316) 881  (959)
Day 7 Number Analyzed 73 participants 68 participants
1208  (1485) 1139  (1590)
Day 10 Number Analyzed 70 participants 66 participants
988  (1135) 1219  (2228)
Day 14 Number Analyzed 70 participants 66 participants
1015  (1520) 1013  (2243)
Day 28/EOS Number Analyzed 32 participants 31 participants
573  (629) 685  (939)
17.Secondary Outcome
Title Log-transformed Levels of LDH
Hide Description Log transformed levels of LDH in blood were assessed as a surrogate marker for organ damage.
Time Frame Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients who had received at least 1 dose of IMP and who had an LDH measurement at the respective timepoints.
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description:
Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID).
Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
Overall Number of Participants Analyzed 88 90
Mean (Standard Error)
Unit of Measure: Log U/L
Day -1 Number Analyzed 78 participants 77 participants
5.91  (0.442) 5.87  (0.489)
Day 3 Number Analyzed 76 participants 76 participants
5.86  (0.440) 5.88  (0.422)
Day 7 Number Analyzed 78 participants 74 participants
5.77  (0.459) 5.75  (0.387)
Day 10 Number Analyzed 72 participants 74 participants
5.66  (0.464) 5.67  (0.401)
Day 14 Number Analyzed 69 participants 71 participants
5.55  (0.467) 5.52  (0.406)
Day 28/EOS Number Analyzed 38 participants 38 participants
5.43  (0.305) 5.50  (0.383)
Time Frame 28 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group A (Active) APN01 Group B (Placebo Control)
Hide Arm/Group Description Patients were treated with APN01 (Recombinant human angiotensin-converting enzyme 2 [rhACE2]) intravenously twice daily (BID). Patients were treated with placebo (physiological saline solution) intravenously twice daily (BID).
All-Cause Mortality
Group A (Active) APN01 Group B (Placebo Control)
Affected / at Risk (%) Affected / at Risk (%)
Total   9/88 (10.23%)      7/90 (7.78%)    
Hide Serious Adverse Events
Group A (Active) APN01 Group B (Placebo Control)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/88 (11.36%)      12/90 (13.33%)    
General disorders     
General physical health deterioration * 1  1/88 (1.14%)  1 1/90 (1.11%)  1
Infections and infestations     
Sepsis * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
Injury, poisoning and procedural complications     
Muscle rupture * 1  0/88 (0.00%)  0 1/90 (1.11%)  1
Nervous system disorders     
Cerebral infarction * 1  0/88 (0.00%)  0 1/90 (1.11%)  1
Haemorrhagic stroke * 1  0/88 (0.00%)  0 1/90 (1.11%)  1
Syncope * 1  0/88 (0.00%)  0 1/90 (1.11%)  1
Renal and urinary disorders     
Renal failure * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
Pulmonary embolism * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
Pulmonary oedema * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
Respiratory distress * 1  0/88 (0.00%)  0 1/90 (1.11%)  1
Respiratory failure * 1  6/88 (6.82%)  6 7/90 (7.78%)  7
Vascular disorders     
Infarction * 1  1/88 (1.14%)  1 1/90 (1.11%)  1
Thrombosis * 1  1/88 (1.14%)  1 0/90 (0.00%)  0
1
Term from vocabulary, MedDRA (23.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group A (Active) APN01 Group B (Placebo Control)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/88 (15.91%)      24/90 (26.67%)    
Investigations     
Alanine aminotransferase increased * 1  10/88 (11.36%)  10 11/90 (12.22%)  11
Blood potassium increased * 1  5/88 (5.68%)  5 4/90 (4.44%)  4
Electrocardiogram QT prolonged * 1  2/88 (2.27%)  2 6/90 (6.67%)  6
Hepatic enzyme increased * 1  0/88 (0.00%)  0 5/90 (5.56%)  5
1
Term from vocabulary, MedDRA (23.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Romana Gugenberger
Organization: APEIRON Biologics AG
Phone: +4366488506236
EMail: romana.gugenberger@apeiron-biologics.com
Layout table for additonal information
Responsible Party: Apeiron Biologics
ClinicalTrials.gov Identifier: NCT04335136    
Other Study ID Numbers: APN01-01-COVID19
First Submitted: April 1, 2020
First Posted: April 6, 2020
Results First Submitted: June 7, 2021
Results First Posted: August 2, 2021
Last Update Posted: August 2, 2021