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

COVID-19 Clinical Trial

— APN01-COVID-19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04335136
• Other study ID #: APN01-01-COVID19
• Status: Completed
• Phase: Phase 2
• Start date: April 30, 2020
• Est. completion date: December 26, 2020

Study information

• Verified date: July 2021
• Source: Apeiron Biologics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: December 26, 2020
• Est. primary completion date: December 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Hospitalized male or female

2. Diagnosed to be COVID-19 POSITIV

3. Signed Inform Consent Form

Exclusion Criteria:

1. Any patient whose clinical condition is deteriorating rapidly

2. Known history of positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody

3. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation

4. Pregnant females as determined by positive serum or urine hCG test prior to dosing

5. Lung transplantation

6. Pre-existing renal failure, i.e. requiring renal replacement therapy with hemodialysis or peritoneal dialysis

7. There are other uncontrolled co-morbidities that increase the risks associated with the study drug administration, that are assessed by the medical expert team as unsuitable

8. Patient in clinical trials for COVID-19 within 30 days before ICF

9. Immunocompromised patients (chemotherapy, HIV, organ transplants, stem cell transplants)

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• RhACE2 APN01
Patients will be treated with APN01 intravenously twice daily (BID).
• Physiological saline solution
Patients will be treated with placebo intravenously twice daily (BID).

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin	Wien
Austria	Medizinische Universität Wien	Wien
Denmark	The National University Hospital, Rigshospitalet	Copenhagen
Denmark	Herlev Gentofte Hospital	Herlev
Denmark	Nordsjællands Hospital	Hillerød
Denmark	Hvidovre Hospital	Hvidovre
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Klinikum rechts der Isar, Technische Universität München	München
Russian Federation	Regional State Budgetary Educational Institution "Clinical Hospital ? 5, Barnaul"	Barnaul
Russian Federation	Moscow State Budgetary Healthcare Institution "City Clinical Hospital ?52 of Health Department of Moscow"	Moscow
Russian Federation	Moscow State Budgetary Healthcare Institution "N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow"	Moscow
Russian Federation	State Healthcare Institution "State Clinical Hspital ? 15 named after O.M. Filatov"	Moscow
Russian Federation	Saint Petersburg SBHI City Hospital 38 named after N A Semashko	Pushkin
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after I.P. Pavlov" HD RF	Ryazan
Russian Federation	Alexandrovskaya Hospital	Saint-Petersburg
Russian Federation	Saint-Petersburg State Budget Healthcare Institution City Hospital 15	Saint-Petersburg
Russian Federation	Federal State Budgetary Educational Institution of Higher Education " Saratov State Medical University named after V.I. Razumovsky" HD RF	Saratov
Russian Federation	Regional State Budgetary Healthcare Institution "Clinical Hospital ?1"	Smolensk
Russian Federation	State budgetary institution of Healthcare of Tver region "Regional clinical hospital"	Tver
Russian Federation	Yaroslavl Regional Clinical Hospital for Military Veterans - International Centre for Gerontological Problems "Healthy Ageing"	Yaroslavl
United Kingdom	Cambridge University Hospitals NHS Trust/University of Cambridge	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Apeiron Biologics

Countries where clinical trial is conducted

Austria,  Denmark,  Germany,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cause-death or Invasive Mechanical Ventilation	The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.	28 days
Secondary	Lactate Dehydrogenase (LDH) Level	Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).	Day 5
Secondary	Mortality	28-day mortality (all cause-death).	28 days
Secondary	Ventilator-free Days (VFD)	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.	28 days
Secondary	Time to Death	Time to death (all causes).	28 days
Secondary	Number of Responders, Defined as =2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28	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.	Day 7, Day 10, Day 14, Day 28
Secondary	Time to Hospital Discharge	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.	Up to 28 days
Secondary	Viral Ribonucleic Acid (RNA).	Viral RNA was assessed in blood samples using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and projected to RNA copies per mL.	Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS)
Secondary	Time to a 2-point Decrease in WHO's 11-Point Score System	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.	Up to 28 days.
Secondary	Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge	The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.	Up to 28 days
Secondary	Time to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge	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.	Up to 28 days
Secondary	PaO2/FiO2 Value	The ratio in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) was assessed by analysis of patient's blood gas.	Day 1, Day 7, Day 10, Day 14, and Day 28
Secondary	Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)	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.	Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of study
Secondary	Lymphocyte Count	Lymphocytes were assessed in blood samples from the patients.	Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Secondary	C-reactive Protein Levels	C-reactive protein was assessed in blood samples from the patients.	Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Secondary	D-Dimer	D-Dimer was assessed in blood samples from the patients.	Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Secondary	Log-transformed Levels of LDH	Log transformed levels of LDH in blood were assessed as a surrogate marker for organ damage.	Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study