Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19
- Conditions
- COVID-19
- Interventions
- Drug: Physiological saline solution
- Registration Number
- NCT04335136
- Lead Sponsor
- Apeiron Biologics
- Brief Summary
Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 185
- Hospitalized male or female
- Diagnosed to be COVID-19 POSITIV
- Signed Inform Consent Form
- Any patient whose clinical condition is deteriorating rapidly
- Known history of positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody
- 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
- Pregnant females as determined by positive serum or urine hCG test prior to dosing
- Lung transplantation
- Pre-existing renal failure, i.e. requiring renal replacement therapy with hemodialysis or peritoneal dialysis
- 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
- Patient in clinical trials for COVID-19 within 30 days before ICF
- Immunocompromised patients (chemotherapy, HIV, organ transplants, stem cell transplants)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A (active) APN01 RhACE2 APN01 Recombinant human angiotensin-converting enzyme 2 (rhACE2) - APN01 Group B (placebo control) Physiological saline solution -
- Primary Outcome Measures
Name Time Method All Cause-death or Invasive Mechanical Ventilation 28 days The primary endpoint was a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge.
- Secondary Outcome Measures
Name Time Method Time to Death 28 days Time to death (all causes).
Mortality 28 days 28-day mortality (all cause-death).
Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge Up to 28 days The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.
C-reactive Protein Levels Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study C-reactive protein was assessed in blood samples from the patients.
D-Dimer Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study D-Dimer was assessed in blood samples from the patients.
Log-transformed Levels of LDH Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study Log transformed levels of LDH in blood were assessed as a surrogate marker for organ damage.
Lactate Dehydrogenase (LDH) Level Day 5 Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).
Viral Ribonucleic Acid (RNA). Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS) Viral RNA was assessed in blood samples using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and projected to RNA copies per mL.
Ventilator-free Days (VFD) 28 days 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 to Hospital Discharge Up to 28 days 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 to a 2-point Decrease in WHO's 11-Point Score System Up to 28 days. 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.Lymphocyte Count Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study Lymphocytes were assessed in blood samples from the patients.
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, Day 10, Day 14, Day 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.Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score) Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of study 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 to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge Up to 28 days 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.PaO2/FiO2 Value Day 1, Day 7, Day 10, Day 14, and Day 28 The ratio in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) was assessed by analysis of patient's blood gas.
Trial Locations
- Locations (22)
State budgetary institution of Healthcare of Tver region "Regional clinical hospital"
🇷🇺Tver, 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
Herlev Gentofte Hospital
🇩🇰Herlev, Denmark
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Moscow State Budgetary Healthcare Institution "City Clinical Hospital №52 of Health Department of Moscow"
🇷🇺Moscow, Russian Federation
Hvidovre Hospital
🇩🇰Hvidovre, Denmark
Cambridge University Hospitals NHS Trust/University of Cambridge
🇬🇧Cambridge, United Kingdom
State Healthcare Institution "State Clinical Hspital № 15 named after O.M. Filatov"
🇷🇺Moscow, Russian Federation
Moscow State Budgetary Healthcare Institution "N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow"
🇷🇺Moscow, Russian Federation
Yaroslavl Regional Clinical Hospital for Military Veterans - International Centre for Gerontological Problems "Healthy Ageing"
🇷🇺Yaroslavl, Russian Federation
The National University Hospital, Rigshospitalet
🇩🇰Copenhagen, Denmark
Nordsjællands Hospital
🇩🇰Hillerød, Denmark
Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin
🇦🇹Wien, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Klinikum rechts der Isar, Technische Universität München
🇩🇪München, Germany
Regional State Budgetary Educational Institution "Clinical Hospital № 5, Barnaul"
🇷🇺Barnaul, 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
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria