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

March 15, 2020 updated by: Yimin LI, The First Affiliated Hospital of Guangzhou Medical University

A Randomized, Open Label, Controlled Clinical Study to Evaluate the Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) in Adult Patients With COVID-19

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

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

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • GCP Office of The First Affiliated Hospital of Guangzhou Medical University

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

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
NO_INTERVENTION: Control group
Standard of care; no placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time course of body temperature (fever)
Time Frame: 14 days
Compare the time course of body temperature (fever) between two groups over time.
14 days
Viral load over time
Time Frame: 14 days
Compare viral load between two groups over time.
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events and severe adverse events
Time Frame: 14 days
14 days
P/F ratio over time
Time Frame: 14 days
PaO2/FiO2 ratio
14 days
Sequential organ failure assessment score(SOFA score) over time
Time Frame: 14 days
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.
14 days
Pulmonary Severity Index (PSI)
Time Frame: 14 days
14 days
Image examination of chest over time
Time Frame: 14 days
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.
14 days
Proportion of subjects who progressed to critical illness or death
Time Frame: 14 days
14 days
Time from first dose to conversion to normal or mild pneumonia
Time Frame: 14 days
14 days
T-lymphocyte counts over time
Time Frame: 14 days
14 days
C-reactive protein levels over time
Time Frame: 14 days
14 days
Angiotensin II (Ang II) changes over time
Time Frame: 14 days
14 days
Angiotensin 1-7 (Ang 1-7) changes over time
Time Frame: 14 days
14 days
Angiotensin 1-5 (Ang 1-5) changes over time
Time Frame: 14 days
14 days
Renin changes over time
Time Frame: 14 days
14 days
Aldosterone changes over time
Time Frame: 14 days
14 days
Angiotensin-converting enzyme (ACE) changes over time
Time Frame: 14 days
14 days
Angiotensin-converting enzyme 2 (ACE2) changes over time
Time Frame: 14 days
14 days
Interleukin 6 (IL-6) changes over time
Time Frame: 14 days
14 days
Interleukin 8 (IL-8) changes over time
Time Frame: 14 days
14 days
Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
Time Frame: 14 days
14 days
Plasminogen activator inhibitor type-1 (PAI-1) changes over time
Time Frame: 14 days
14 days
Von willebrand factor (vWF) changes over time
Time Frame: 14 days
14 days
Tumor necrosis factor-α (TNF-α) changes over time
Time Frame: 14 days
14 days
Soluble receptor for advanced glycation end products (sRAGE) changes over time
Time Frame: 14 days
14 days
Surfactant protein-D (SP-D) changes over time
Time Frame: 14 days
14 days
Angiopoietin-2 changes over time
Time Frame: 14 days
14 days

Collaborators and Investigators

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

Sponsor

The First Affiliated Hospital of Guangzhou Medical University

Investigators

  • Principal Investigator: Yimin Li, PhD, MD, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (ANTICIPATED)

February 1, 2020

Primary Completion (ANTICIPATED)

April 1, 2020

Study Completion (ANTICIPATED)

April 1, 2020

Study Registration Dates

First Submitted

February 21, 2020

First Submitted That Met QC Criteria

February 25, 2020

First Posted (ACTUAL)

February 27, 2020

Study Record Updates

Last Update Posted (ACTUAL)

March 17, 2020

Last Update Submitted That Met QC Criteria

March 15, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIRH-APN01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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