search
Back to results

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

Primary Purpose

COVID-19

Status
Withdrawn
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Recombinant human angiotensin-converting enzyme 2 (rhACE2)
Sponsored by
The First Affiliated Hospital of Guangzhou Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring SARS-CoV-2, Renin-angiotensin-system (RAS)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 mmHg（1 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

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

Sites / Locations

  • GCP Office of The First Affiliated Hospital of Guangzhou Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

rhACE2 group

Control group

Arm Description

0.4 mg/kg IV BID for 7 days (unblinded) + standard of care

Standard of care; no placebo

Outcomes

Primary Outcome Measures

Time course of body temperature (fever)
Compare the time course of body temperature (fever) between two groups over time.
Viral load over time
Compare viral load between two groups over time.

Secondary Outcome Measures

P/F ratio over time
PaO2/FiO2 ratio
Sequential organ failure assessment score(SOFA score) over time
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.
Pulmonary Severity Index (PSI)
Image examination of chest over time
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.
Proportion of subjects who progressed to critical illness or death
Time from first dose to conversion to normal or mild pneumonia
T-lymphocyte counts over time
C-reactive protein levels over time
Angiotensin II (Ang II) changes over time
Angiotensin 1-7 (Ang 1-7) changes over time
Angiotensin 1-5 (Ang 1-5) changes over time
Renin changes over time
Aldosterone changes over time
Angiotensin-converting enzyme (ACE) changes over time
Angiotensin-converting enzyme 2 (ACE2) changes over time
Interleukin 6 (IL-6) changes over time
Interleukin 8 (IL-8) changes over time
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
Von willebrand factor (vWF) changes over time
Tumor necrosis factor-α (TNF-α) changes over time
Soluble receptor for advanced glycation end products (sRAGE) changes over time
Surfactant protein-D (SP-D) changes over time
Angiopoietin-2 changes over time
Frequency of adverse events and severe adverse events

Full Information

First Posted
February 21, 2020
Last Updated
March 15, 2020
Sponsor
The First Affiliated Hospital of Guangzhou Medical University
search

1. Study Identification

Unique Protocol Identification Number
NCT04287686
Brief Title
Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19
Official Title
A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Without CDE Approval
Study Start Date
February 2020 (Anticipated)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
April 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Guangzhou Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an open label, randomized, controlled, pilot clinical study in patients with COVID-19, to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase 2B trial is warranted.
Detailed Description
This is a small pilot study investigating whether there is any efficacy signal that warrants a larger Phase 2B trial, or any harm that suggests that such a trial should not be done. It is not expected to produce statistically significant results in the major endpoints. The investigators will examine all of the biologic, physiological, and clinical data to determine whether a Phase 2B trial is warranted. Primary efficacy analysis will be carried only on patients receiving at least 4 doses of active drug. Safety analysis will be carried out on all patients receiving at least one dose of active drug. It is planned to enroll more than or equal to 24 subjects with COVID-19. It is expected to have at least 12 evaluable patients in each group. Experimental group: 0.4 mg/kg rhACE2 IV BID and standard of care Control group: standard of care Intervention duration: up to 7 days of therapy No planned interim analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
SARS-CoV-2, Renin-angiotensin-system (RAS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
2-arm pilot study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rhACE2 group
Arm Type
Experimental
Arm Description
0.4 mg/kg IV BID for 7 days (unblinded) + standard of care
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Standard of care; no placebo
Intervention Type
Drug
Intervention Name(s)
Recombinant human angiotensin-converting enzyme 2 (rhACE2)
Intervention Description
In this study, the experimental group will receive 0.4 mg/kg rhACE2 IV BID for 7 days.
Primary Outcome Measure Information:
Title
Time course of body temperature (fever)
Description
Compare the time course of body temperature (fever) between two groups over time.
Time Frame
14 days
Title
Viral load over time
Description
Compare viral load between two groups over time.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
P/F ratio over time
Description
PaO2/FiO2 ratio
Time Frame
14 days
Title
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
Title
Pulmonary Severity Index (PSI)
Time Frame
14 days
Title
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
Title
Proportion of subjects who progressed to critical illness or death
Time Frame
14 days
Title
Time from first dose to conversion to normal or mild pneumonia
Time Frame
14 days
Title
T-lymphocyte counts over time
Time Frame
14 days
Title
C-reactive protein levels over time
Time Frame
14 days
Title
Angiotensin II (Ang II) changes over time
Time Frame
14 days
Title
Angiotensin 1-7 (Ang 1-7) changes over time
Time Frame
14 days
Title
Angiotensin 1-5 (Ang 1-5) changes over time
Time Frame
14 days
Title
Renin changes over time
Time Frame
14 days
Title
Aldosterone changes over time
Time Frame
14 days
Title
Angiotensin-converting enzyme (ACE) changes over time
Time Frame
14 days
Title
Angiotensin-converting enzyme 2 (ACE2) changes over time
Time Frame
14 days
Title
Interleukin 6 (IL-6) changes over time
Time Frame
14 days
Title
Interleukin 8 (IL-8) changes over time
Time Frame
14 days
Title
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
Time Frame
14 days
Title
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
Time Frame
14 days
Title
Von willebrand factor (vWF) changes over time
Time Frame
14 days
Title
Tumor necrosis factor-α (TNF-α) changes over time
Time Frame
14 days
Title
Soluble receptor for advanced glycation end products (sRAGE) changes over time
Time Frame
14 days
Title
Surfactant protein-D (SP-D) changes over time
Time Frame
14 days
Title
Angiopoietin-2 changes over time
Time Frame
14 days
Title
Frequency of adverse events and severe adverse events
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Fever: Axillary temperature >37.3℃ 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 mmHg（1 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 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) Appropriate ethics approval and ICF 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yimin Li, PhD, MD
Organizational Affiliation
The First Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
GCP Office of The First Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510120
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
32522846
Citation
Zhang X, Li S, Niu S. ACE2 and COVID-19 and the resulting ARDS. Postgrad Med J. 2020 Jul;96(1137):403-407. doi: 10.1136/postgradmedj-2020-137935. Epub 2020 Jun 10.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs