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

July 29, 2021 updated by: Apeiron Biologics
Recombinant human angotensin-converting enzyme 2 (rhACE2) as a treatment for patients with COVID-19 to block viral entry and decrease viral replication.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
185

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria
        • Medizinische Universität Innsbruck
      • Wien, Austria
        • Medizinische Universität Wien
      • Wien, Austria
        • Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin
  • Denmark
      • Copenhagen, Denmark
        • The National University Hospital, Rigshospitalet
      • Herlev, Denmark, 2730
        • Herlev Gentofte Hospital
      • Hillerød, Denmark, 3400
        • Nordsjællands Hospital
      • Hvidovre, Denmark, 2650
        • Hvidovre Hospital
  • Germany
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • München, Germany
        • Klinikum rechts der Isar, Technische Universität München
  • Russian Federation
      • Barnaul, Russian Federation, 656045
        • Regional State Budgetary Educational Institution "Clinical Hospital № 5, Barnaul"
      • Moscow, Russian Federation, 111539
        • State Healthcare Institution "State Clinical Hspital № 15 named after O.M. Filatov"
      • Moscow, Russian Federation, 123182
        • Moscow State Budgetary Healthcare Institution "City Clinical Hospital №52 of Health Department of Moscow"
      • Moscow, Russian Federation, 129090
        • Moscow State Budgetary Healthcare Institution "N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow"
      • Pushkin, Russian Federation, 196600
        • Saint Petersburg SBHI City Hospital 38 named after N A Semashko
      • Ryazan, Russian Federation, 390026
        • Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after I.P. Pavlov" HD RF
      • Saint-Petersburg, Russian Federation, 193312
        • Alexandrovskaya Hospital
      • Saint-Petersburg, Russian Federation, 198205
        • Saint-Petersburg State Budget Healthcare Institution City Hospital 15
      • Saratov, Russian Federation, 410054
        • Federal State Budgetary Educational Institution of Higher Education " Saratov State Medical University named after V.I. Razumovsky" HD RF
      • Smolensk, Russian Federation, 214006
        • Regional State Budgetary Healthcare Institution "Clinical Hospital №1"
      • Tver, Russian Federation, 170036
        • State Budgetary Institution of Healthcare of Tver region "Regional clinical hospital"
      • Yaroslavl, Russian Federation, 150047
        • Yaroslavl Regional Clinical Hospital for Military Veterans - International Centre for Gerontological Problems "Healthy Ageing"
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Cambridge University Hospitals NHS Trust/University of Cambridge

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group A (active) APN01
Recombinant human angiotensin-converting enzyme 2 (rhACE2) - APN01
Drug: RhACE2 APN01
Patients will be treated with APN01 intravenously twice daily (BID).
Other Names:
  • APN01
  • Recombinant human angiotensin-converting enzyme 2
Placebo Comparator: Group B (placebo control)
Drug: Physiological saline solution
Patients will be treated with placebo intravenously twice daily (BID).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
All Cause-death or Invasive Mechanical Ventilation
Time Frame: 28 days
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Lactate Dehydrogenase (LDH) Level
Time Frame: Day 5
Log transformed levels of LDH at Day 5 as a surrogate marker for organ damage (powered secondary endpoint).
Day 5
Mortality
Time Frame: 28 days
28-day mortality (all cause-death).
28 days
Ventilator-free Days (VFD)
Time Frame: 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.
28 days
Time to Death
Time Frame: 28 days
Time to death (all causes).
28 days
Number of Responders, Defined as ≥2 Improvement in World Health Organization (WHO)'s 11-Point Score System at Days 7, 10, 14 and 28
Time Frame: 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.
Day 7, Day 10, Day 14, Day 28
Time to Hospital Discharge
Time Frame: 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.
Up to 28 days
Viral Ribonucleic Acid (RNA).
Time Frame: 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.
Day 1, Day 3, Day 5, Day 7, Day 14, and Day 28/End of study (EOS)
Time to a 2-point Decrease in WHO's 11-Point Score System
Time Frame: 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.
Up to 28 days.
Number of Patients With Any Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Time Frame: Up to 28 days
The number of patients receiving mechanical ventilation and supplemental oxygen was evaluated.
Up to 28 days
Time to First Use of Invasive Mechanical Ventilation up to 28 Days or Hospital Discharge
Time Frame: 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.
Up to 28 days
PaO2/FiO2 Value
Time Frame: 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.
Day 1, Day 7, Day 10, Day 14, and Day 28
Modified Sequential Organ Failure Assessment Score (mSOFA Score, Total Score)
Time Frame: 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.
Day -1 (Screening), Day 7, Day 10, Day 14, Day 28/End of study
Lymphocyte Count
Time Frame: Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Lymphocytes were assessed in blood samples from the patients.
Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
C-reactive Protein Levels
Time Frame: 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.
Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
D-Dimer
Time Frame: 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.
Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study
Log-transformed Levels of LDH
Time Frame: 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.
Day -1, Day 3, Day 7, Day 10, Day 14, Day 28/End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Apeiron Biologics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Henning Bundgaard, MD., Cap. Region's Unit of Inherited Cardiac Diseases, Faculty Health&Medical

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 26, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 26, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • APN01-01-COVID19

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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