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Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19

Trial Profile

Recombinant human angiotensin-converting enzyme 2 (rhACE2) as a treat-ment for patients with COVID-19

Status: Completed
Phase of Trial: Phase II

Latest Information Update: 12 Mar 2021

At a glance

  • Drugs Alunacedase alfa (Primary)
  • Indications COVID-19 respiratory infection
  • Focus Therapeutic Use
  • Acronyms APN01-COVID-19
  • Sponsors Apeiron Biologics
  • Most Recent Events

    • 12 Mar 2021 Primary endpoint has been met. (Cause of death or invasive mechanical ventilation), according to an Apeiron Biologics Media Release.
    • 12 Mar 2021 Results published in the Apeiron Biologics Media Release
    • 21 Jan 2021 Status changed from recruiting to completed.

Trial Overview

Outcome

Primary endpoint met - positive

Purpose

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

Primary Endpoints

Met on 12 Mar 2021

Cause of death or invasive mechanical ventilation

description: The primary endpoint is a composite endpoint of all cause-death or invasive mechanical ventilation up to 28 days or hospital discharge
time_frame: 28 days [1]

Other Endpoints

LDH level

description: Log transformed levels of Lactate dehydrogenase (LDH) at day 5 as a surrogate marker for organ damage (powered secondary endpoint
time_frame: Day 5

Mortality

description: 28-day mortality (all cause-death)
time_frame: 28 days

VFD

description: Ventilator-free days (VFD) up to 28 days or hospital discharge
time_frame: 28 days

Time to death

description: Time to death (all causes)
time_frame: 28 days [2]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 respiratory infection treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 200

    Actual: 200

  • Sex male & female
  • Age Group 18-80 years; adult; elderly

Patient Inclusion Criteria

1. Hospitalized male or female 2. Diagnosed to be COVID-19 POSITIV 3. Signed Inform Consent Form

Patient 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)

Trial Details

Identifiers

Identifier Owner
NCT04335136 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001172-15 European Clinical Trials Database
APN01-01COVID19 -

Organisations

  • Sponsors Apeiron Biologics
  • Affiliations Apeiron Biologics

Trial Dates

  • Initiation Dates

    Planned : 01 Apr 2020

    Actual : 30 Apr 2020

  • Primary Completion Dates

    Planned : 01 Dec 2020

    Actual : 26 Dec 2020

  • End Dates

    Planned : 01 Dec 2020

    Actual : 26 Dec 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Austria; Denmark; England; Germany; Russia; United Kingdom; USA
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
Alunacedase alfaPrimary Drug Intravenous Infusion

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 Name: APN01, Recombinant human angiotensin-converting enzyme 2

Group B (placebo control)

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

Results

Therapeutic efficacy

Results from a phase II trial in patients with COVID-2019 showed that fewer patients treated with alunacedase alfa (n=9) died or received invasive ventilation compared with placebo (n=12), although statistical significance was not achieved due to the low total number of events. Standard of care improved, resulted in fewer deaths and less use of invasive mechanical ventilation. A reduction in viral RNA load over time was observed in the alunacedase alfa treatment group [1] . Earlier results showed that the first patient treated with alunacedase alfa observed significant clinical improvement with an adaptive immune response. Alunacedase alfa effectively blocked the spike glycoprotein in COVID-19 infection. Alunacedase alfa (soluble ACE2) infusion showed the expected enzymatic activity and modulation of the renin angiotensin system. Alunacedase alfa infusion correlated with a gradual reduction in levels of multiple disease relevant inflammatory mediators over the studied time period. The APN 01 infusion also correlated with a rapid loss of detectable viremia and slightly delayed reduction in viral titers in tracheal samples and nasopharyngeal swaps. Alunacedase alfa infusion was fully compatible with an adaptive immune response and the development of high titers of neutralising antibodies against SARS-CoV-2 [3] .

Adverse events

Results from a phase II trial in patients with COVID-2019 infections, showed that treatment with alunacedase alfa was safe and well tolerated and no drug-related severe adverse events were observed [1] .

Pharmacodynamics

Results from a phase II trial in patients with COVID-2019 infections showed that treatment with alunacedase alfa reduced plasma levels of Ang II compared to control group. Alunacedase alfa treatment showed increased Ang 1-7 and Ang 1-5 levels while no increase in these anti-inflammatory factors was seen in the placebo group. Suppression of Ang II and increase of Ang 1-7 and Ang 1-5 in addition to the observed reduction in viral RNA load under alunacedase alfa treatment [1] .

Publications

  1. Apeiron Biologics. APEIRON's APN01 shows clinical benefits for severely ill COVID-19 patients in phase 2 trial. Media-Rel 2021;.

    Media Release

Authors

Author Total Publications First Author Last Author
Apeiron Biologics 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Alexander Popov, MD Saint Petersburg SBHI City Hospital 38 named after N A Semashko Russia
Alexander Zoufaly, Priv.-Doz. Dr. Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin Austria
Boris Goloshchekin, MD Saint-Petersburg State Budget Healthcare Institution City Hospital 15 Russia
Christian Søborg Herlev Gentofte Hospital Denmark
Christoph D. Spinner, PD DR. med. Klinikum rechts der Isar, Technische Universität München Germany
Claudia Haider, Mag.
43 1 8656577 110
claudia.haider@apeiron-biologics.com
show details
Apeiron Biologics
-
Daria Formina, MD Moscow State Budgetary Healthcare Institution "City Clinical Hospital №52 of Health Department of Moscow" Russia
Elena Simakina, MD Regional State Budgetary Healthcare Institution "Clinical Hospital №1" Russia
Galina Trufanova, MD State budgetary institution of Healthcare of Tver region "Regional clinical hospital" Russia
Günter Weiss, Univ.-Prof. Dr. Medizinische Universität Innsbruck Austria
Henning Bundgaard, MD. Cap. Region's Unit of Inherited Cardiac Diseases, Faculty Health&Medical
-
Ivan Gordeev, MD State Healthcare Institution "State Clinical Hspital № 15 named after O.M. Filatov" Russia
Jan Gerstoft, Prof. Dr. med. The National University Hospital, Rigshospitalet Denmark
Jeffrey Reeves, MD Norton Infectious Disease Institute USA
Joseph Cheriyan, MD Cambridge University Hospitals NHS Trust/University of Cambridge United-Kingdom
Maria Mozheiko Yaroslavl Regional Clinical Hospital for Military Veterans - International Centre for Gerontological Problems "Healthy Ageing" Russia
Oleg Burlaka, MD Alexandrovskaya Hospital Russia
Peter Hou, MD Brigham and Women's Hospital USA
Roman Ullrich, Prof. Dr. Medizinische Universität Wien Austria
Sergey Zhuravel, MD Moscow State Budgetary Healthcare Institution "N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow" Russia
Sonja Höller, Dr.
43 1 865 65 77 128
sonja.hoeller@apeiron-biologics.com
show details
, Apeiron Biologics
-
SPONSOR
Campus-Vienna-Biocenter 5,
Vienna, 1030, Austria.
sonja.hoeller@apeiron-biologics.com
show details
APEIRON Biologics AG Austria
Stefan Schmiedel, Dr. med. Universitätsklinikum Hamburg-Eppendorf Germany
Tatyana Martynenko Regional State Budgetary Educational Institution "Clinical Hospital № 5, Barnaul" Russia
Thomas L. Benfield, Prof. Hvidovre Hospital Denmark
Troels B. Knudsen Nordsjællands Hospital Denmark
Vladimir Martynov, MD Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after I.P. Pavlov" HD RF Russia

Centres

Centre Name Location Trial Centre Country
-
-
-
Alexandrovskaya Hospital Saint-Petersburg Russia
Apeiron Biologics
-
-
APEIRON Biologics AG Vienna Austria
Brigham and Women's Hospital Boston, Massachusetts USA
Cambridge University Hospitals NHS Trust/University of Cambridge Cambridge United-Kingdom
Cap. Region's Unit of Inherited Cardiac Diseases, Faculty Health&Medical
-
-
Federal State Budgetary Educational Institution of Higher Education " Saratov State Medical University named after V.I. Razumovsky" HD RF Saratov Russia
Federal State Budgetary Educational Institution of Higher Education "Ryazan State Medical University named after I.P. Pavlov" HD RF Ryazan Russia
Herlev Gentofte Hospital Herlev Denmark
Hvidovre Hospital Hvidovre Denmark
Kaiser Franz Josef Spital, 4. Medizinische Abteilung mit Infektions- und Tropenmedizin Wien Austria
Klinikum rechts der Isar, Technische Universität München München Germany
Medizinische Universität Innsbruck Innsbruck Austria
Medizinische Universität Wien Wien Austria
Moscow State Budgetary Healthcare Institution "City Clinical Hospital №52 of Health Department of Moscow" Moscow Russia
Moscow State Budgetary Healthcare Institution "N.V. Sklifosovsky Research Institute for Emergency Medicine of Health Department of Moscow" Moscow Russia
Nordsjællands Hospital Hillerød Denmark
Norton Infectious Disease Institute Louisville, Kentucky USA
Regional State Budgetary Educational Institution "Clinical Hospital № 5, Barnaul" Barnaul Russia
Regional State Budgetary Healthcare Institution "Clinical Hospital №1" Smolensk Russia
Saint Petersburg SBHI City Hospital 38 named after N A Semashko Pushkin Russia
Saint-Petersburg State Budget Healthcare Institution City Hospital 15 Saint-Petersburg Russia
State budgetary institution of Healthcare of Tver region "Regional clinical hospital" Tver Russia
State Healthcare Institution "State Clinical Hspital № 15 named after O.M. Filatov" Moscow Russia
The National University Hospital, Rigshospitalet Copenhagen Denmark
Universitätsklinikum Hamburg-Eppendorf Hamburg Germany
Yaroslavl Regional Clinical Hospital for Military Veterans - International Centre for Gerontological Problems "Healthy Ageing" Yaroslavl Russia

Trial History

Event Date Event Type Comment
12 Mar 2021 Endpoint met Primary endpoint has been met. (Cause of death or invasive mechanical ventilation), according to an Apeiron Biologics Media Release. Updated 16 Mar 2021
12 Mar 2021 Results Results published in the Apeiron Biologics Media Release Updated 16 Mar 2021
01 Feb 2021 Other trial event Last checked against the European Clinical Trials Database record Updated 01 Feb 2021
27 Jan 2021 Other trial event Last checked against ClinicalTrials.gov record. Updated 27 Jan 2021
21 Jan 2021 Status change - completed Status changed from recruiting to completed. Updated 27 Jan 2021
15 Jan 2021 Other trial event This trial has been completed in Denmark, according to European Clinical Trials Database record. (2020-12-26) Updated 15 Jan 2021
07 Jan 2021 Other trial event This trial has been completed in Germany, according to European Clinical Trials Database record. Updated 07 Jan 2021
26 Nov 2020 Other trial event This trial has been Discontinued in Denmark, according to European Clinical Trials Database record. Updated 30 Nov 2020
30 Sep 2020 Completion date Planned End Date changed from 1 Nov 2020 to 1 Dec 2020. Updated 18 Jan 2021
30 Sep 2020 Other trial event Planned primary completion date changed from 1 Sep 2020 to 1 Dec 2020. Updated 18 Jan 2021
24 Sep 2020 Other trial event According to an Apeiron Biologics media release, Case study from promising first COVID-19 patient treatment with APN01 published in the peer-reviewed journal The Lancet Respiratory Medicine, supports this ongoing clinical trial Updated 28 Sep 2020
05 Jun 2020 Other trial event According to an Apeiron Biologics media release, the company plans to expand the trial to USA and Russia. Updated 05 Jun 2020
04 May 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 06 May 2020
08 Apr 2020 Other trial event New source identified and integrated: (ClinicalTrials.gov: US National Institutes of Health: NCT04335136). Updated 08 Apr 2020
07 Apr 2020 Other trial event New source identified and integrated: (European Clinical Trials Database: EudraCT2020-001172-15). Updated 07 Apr 2020
03 Apr 2020 New trial record New trial record Updated 03 Apr 2020
02 Apr 2020 Other trial event According to an Apeiron Biologics media release, the University Medical Center Hamburg-Eppendorf and the Klinikum rechts der Isar of the Technical University of Munich; the Medical University of Vienna, the Kaiser Franz-Josef-Spital, Vienna, the Medical University of Innsbruck and the University Medical Center Salzburg; the National University Hospital, Rigshospitalet, the Herlev Gentofte Hospital, the Hvido Hospital, and the Nordsaellands Hospital will participate in this study. Updated 03 Apr 2020
02 Apr 2020 Other trial event According to an Apeiron Biologics media release, the Austrian Government has agreed to fund a significant portion of this trial. Prof. Henning Bundgaard is the principal investigator of this study. Updated 03 Apr 2020
02 Apr 2020 Other trial event According to an Apeiron Biologics media release, the company announced that it has received regulatory approvals in Austria, Germany and Denmark to initiate a Phase II clinical trial of APN01 to treat COVID-19 and the first patients are expected to be dosed shortly. Updated 03 Apr 2020

References

  1. Apeiron Biologics. APEIRON's APN01 shows clinical benefits for severely ill COVID-19 patients in phase 2 trial. Media-Rel 2021;.

    Media Release
  2. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  3. Apeiron Biologics. THE LANCET publishes promising data of APEIRON's APN01 (rhsACE2) to treat COVID-19 in named patient use. Media-Rel 2020;.

    Media Release
  4. Apeiron Biologics. APEIRON Biologics Initiates Phase II Clinical Trial of APN01 for Treatment of COVID-19. Media-Rel 2020;.

    Media Release
  5. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  6. Apeiron Biologics. APEIRON Biologics closes oversubscribed financing round of EUR 17.5 million for the development of APN01 against COVID-19. Media-Rel 2020;.

    Media Release
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