A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19
Latest Information Update: 04 Nov 2021
At a glance
- Drugs Alunacedase alfa (Primary)
- Indications COVID 2019 infections
- Focus Therapeutic Use
- 15 Mar 2020 Status changed from not yet recruiting to withdrawn prior to enrolment.
- 27 Feb 2020 New trial record
- 26 Feb 2020 According to an Apeiron Biologics media release, data from this trial will be assessed to ascertain whether a Phase 2B clinical trial in a larger number of patients is warranted.
Most Recent Events
Trial Overview
Purpose
This pilot investigator initiated randomized, unblinded dual-arm trial to evaluate the impact of rhACE2 on biological, physiologic, and clinical outcomes, as well as safety in patients with severe SARS-CoV-2 infection. Patients will be treated for seven days to obtain preliminary data. After seven days of treatment, the trial data will be evaluated and potential further clinical development will be assessed by APEIRON and the IIT team.
Comments
According to clinical.gov, trial was withdrawn, as there was no CDE approval for trial.
Primary Endpoints
Time course of body temperature (fever)
description: Compare the time course of body temperature (fever) between two groups over time.
time_frame: 14 days
Viral load over time
description: Compare viral load between two groups over time.
time_frame: 14 days
Other Endpoints
P/F ratio over time
description: PaO2/FiO2 ratio
time_frame: 14 days
Sequential organ failure assessment score(SOFA score) over time
description: SOFA, including assessment of respiratory, blood, liver, circulatory, nerve, kidney, from 0 to 4 scores in each systems, the higher scores mean a worse outcome.
time_frame: 14 days
Pulmonary Severity Index (PSI)
time_frame: 14 days
Image examination of chest over time
description: Based on radiologist's assessment of inflammatory exudative disease, category as follows: significant improvement, partial improvement, no improvement, increase of partial exudation, significant increase in exudation, unable to judge.
time_frame: 14 days
Proportion of subjects who progressed to critical illness or death
time_frame: 14 days
Time from first dose to conversion to normal or mild pneumonia
time_frame: 14 days
T-lymphocyte counts over time
time_frame: 14 days
C-reactive protein levels over time
time_frame: 14 days
Angiotensin II (Ang II) changes over time
time_frame: 14 days
Angiotensin 1-7 (Ang 1-7) changes over time
time_frame: 14 days
Angiotensin 1-5 (Ang 1-5) changes over time
time_frame: 14 days
Renin changes over time
time_frame: 14 days
Aldosterone changes over time
time_frame: 14 days
Angiotensin-converting enzyme (ACE) changes over time
time_frame: 14 days
Angiotensin-converting enzyme 2 (ACE2) changes over time
time_frame: 14 days
Interleukin 6 (IL-6) changes over time
time_frame: 14 days
Interleukin 8 (IL-8) changes over time
time_frame: 14 days
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
time_frame: 14 days
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
time_frame: 14 days
Von willebrand factor (vWF) changes over time
time_frame: 14 days
Tumor necrosis factor-α (TNF-α) changes over time
time_frame: 14 days
Soluble receptor for advanced glycation end products (sRAGE) changes over time
time_frame: 14 days
Surfactant protein-D (SP-D) changes over time
time_frame: 14 days
Angiopoietin-2 changes over time
time_frame: 14 days
Frequency of adverse events and severe adverse events
time_frame: 14 days [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID 2019 infections | treatment | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04287686 | ACE2 | Brief Title, Official Title, Outcome Measure |
| Aldosterone | Outcome Measure | |
| Angiopoietin 2 (ANGPT2) | Outcome Measure | |
| Angiotensin II | Outcome Measure | |
| Angiotensin-converting enzyme (ACE | Outcome Measure | |
| C-reactive protein (CRP) | Outcome Measure | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| Interleukin-8 (IL-8) | Outcome Measure | |
| PAI-1 | Outcome Measure | |
| RAGE | Outcome Measure | |
| Renin | Outcome Measure | |
| serpin family B member 2 | Outcome Measure | |
| Surfactant protein D | Outcome Measure | |
| TNFRSF1B | Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Outcome Measure | |
| Von Willebrand factor | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 24
Actual: 0
- Sex male & female
- Age Group 18-80 years; adult; elderly
Patient Inclusion Criteria
1. Laboratory diagnosis: - Respiratory specimen is positive for SARS-CoV-2 nucleic acid by RT-PCR; OR, - The viral gene sequencing of the respiratory specimen is highly homologous to known novel coronavirus. 2. Fever: Axillary temperature >37.3℃ 3. Respiratory variables (meets one of the following criteria): - Respiratory rate: RR ≥25 breaths/min - Oxygen saturation ≤93% at rest on room air - PaO2/FiO2 ≤300 mmHg1 mmHg=0.133 KPa - Pulmonary imaging showed that the lesions progressed more than 50% within 24-48 hours, and the patients were managed as severe 4. HBsAg negative, or HBV DNA ≤10^4 copy/ml if HBsAg positive; anti-HCV negative; HIV negative two weeks prior to signed Informed Consent Form (ICF) 5. Appropriate ethics approval and 6. ICF
Patient Exclusion Criteria
- Age <18 years; Age >80 years - Pregnant or breast feeding woman or with positive pregnancy test result - P/F <100 mmHg - Moribund condition (death likely in days) or not expected to survive for >7 days - Refusal by attending MD - Not hemodynamically stable in the preceding 4 hours (MAP ≤65 mmHg, or SAP <90 mmHg, DAP <60 mmHg, vasoactive agents are required) - Patient on invasive mechanical ventilation or ECMO - Patient in other therapeutic clinical trial within 30 days before ICF - Receive any other ACE inhibitors (ACEI), angiotensin-receptor blockers (ARB) treatment within 7 days before ICF - Chronic immunosuppression: current autoimmune diseases or patients who received immunotherapy within 30 days before ICF - Hematologic malignancy (lymphoma, leukemia, multiple myeloma) - Other patient characteristics (not thought to be related to underlying COVID-19) that portend a very poor prognosis (e.g, severe liver failure, and ect) - Known allergy to study drug or its ingredients related to renin-angiotensin system (RAS), or frequent and/or severe allergic reactions with multiple medications - Other uncontrolled diseases, as judged by investigators - Body weight ≥85 kg
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04287686 | ClinicalTrials.gov: US National Institutes of Health |
| GIRH-APN01 | - |
Organisations
- Affiliations Apeiron Biologics
Trial Dates
-
Initiation Dates
Planned : 01 Feb 2020
-
Primary Completion Dates
Planned : 01 Apr 2020
-
End Dates
Planned : 01 Apr 2020
Other Details
- Design open; parallel; prospective; randomised
- Phase of Trial Phase II
- Location China
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| Alunacedase alfaPrimary Drug | Intravenous |
-
|
rhACE2 group
0.4 mg/kg IV BID for 7 days (unblinded) + standard of care
Drug: Recombinant human angiotensin-converting enzyme 2 (rhACE2) (In this study, the experimental group will receive 0.4 mg/kg rhACE2 IV BID for 7 days.)
Control group
Standard of care; no placebo
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Xinyun Yang, MD
020-83062338
show details
gyfygcp@163.com |
GCP Office of The First Affiliated Hospital of Guangzhou Medical University | China |
|
Yimin Li, PhD, MD
+8613533569161
show details
dryiminli@vip.163.com |
The First Affiliated Hospital of Guangzhou Medical University |
-
|
|
Yonghao Xu, PhD, MD
+8613828409707
show details
dryonghao@163.com |
-
|
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
-
|
-
|
| GCP Office of The First Affiliated Hospital of Guangzhou Medical University | Guangzhou, Guangdong | China |
| The First Affiliated Hospital of Guangzhou Medical University |
-
|
-
|
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 18 Mar 2020 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 18 Mar 2020 |
| 17 Mar 2020 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 15 Mar 2020 | Status change - withdrawn prior to enrolment | Status changed from not yet recruiting to withdrawn prior to enrolment. Updated 18 Mar 2020 |
| 04 Mar 2020 | Other trial event | New source identified and integrated (ClinicalTrials.gov record; NCT04287686) Updated 04 Mar 2020 |
| 27 Feb 2020 | New trial record | New trial record Updated 27 Feb 2020 |
| 26 Feb 2020 | Other trial event | According to an Apeiron Biologics media release, data from this trial will be assessed to ascertain whether a Phase 2B clinical trial in a larger number of patients is warranted. Updated 27 Feb 2020 |
| 26 Feb 2020 | Other trial event | According to an Apeiron Biologics media release,This trial cooperation has been supported by Dr. Liqun Zhang and team of Angalpharma Co., Ltd (Suzhou, China), for coordinating the Chinese clinical trial with the support of dMed Pharmaceutical Co., a CRO team based in China. Updated 27 Feb 2020 |
| 26 Feb 2020 | Other trial event | According to an Apeiron Biologics media release, this trial is being supported by by a global team of leading experts: Prof. Nanshan Zhong and Prof. Yimin Li, both of the Guangzhou Institute of Respiratory Health and leading physicians in fight against COVID-19 in China, will oversee the trial; and Prof. Josef Penninger, Scientific Director and Professor of the Life Science Institute of the University of British Columbia, Canada. Updated 27 Feb 2020 |
| 26 Feb 2020 | Other trial event | According to an Apeiron Biologics media release, this trial is being supported by by a global team of leading experts: Intensive care specialist, Prof. Arthur Slutsky, Scientist, St. Michael's Hospital, Toronto, and Prof. of Medicine, Surgery and Biomedical Engineering at the University of Toronto (Toronto, Canada) and Prof. Haibo Zhang, Prof. of Anesthesiology, St. Michael's Hospital, University of Toronto. Updated 27 Feb 2020 |
| 25 Feb 2020 | Status change - not yet recruiting | Status changed from planning to not yet recruiting. Updated 04 Mar 2020 |
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Apeiron Biologics. APEIRON's respiratory drug product to start pilot clinical trial to treat coronavirus disease COVID-19 in China. Media-Rel 2020;.
Media Release
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