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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04287686
Recruitment Status : Withdrawn (Without CDE Approval)
First Posted : February 27, 2020
Last Update Posted : March 17, 2020
Sponsor:
Information provided by (Responsible Party):
Yimin LI, The First Affiliated Hospital of Guangzhou Medical University

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Recombinant human angiotensin-converting enzyme 2 (rhACE2) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2-arm pilot study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2020

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



Primary Outcome Measures :
  1. Time course of body temperature (fever) [ Time Frame: 14 days ]
    Compare the time course of body temperature (fever) between two groups over time.

  2. Viral load over time [ Time Frame: 14 days ]
    Compare viral load between two groups over time.


Secondary Outcome Measures :
  1. P/F ratio over time [ Time Frame: 14 days ]
    PaO2/FiO2 ratio

  2. 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.

  3. Pulmonary Severity Index (PSI) [ Time Frame: 14 days ]
  4. 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.

  5. Proportion of subjects who progressed to critical illness or death [ Time Frame: 14 days ]
  6. Time from first dose to conversion to normal or mild pneumonia [ Time Frame: 14 days ]
  7. T-lymphocyte counts over time [ Time Frame: 14 days ]
  8. C-reactive protein levels over time [ Time Frame: 14 days ]
  9. Angiotensin II (Ang II) changes over time [ Time Frame: 14 days ]
  10. Angiotensin 1-7 (Ang 1-7) changes over time [ Time Frame: 14 days ]
  11. Angiotensin 1-5 (Ang 1-5) changes over time [ Time Frame: 14 days ]
  12. Renin changes over time [ Time Frame: 14 days ]
  13. Aldosterone changes over time [ Time Frame: 14 days ]
  14. Angiotensin-converting enzyme (ACE) changes over time [ Time Frame: 14 days ]
  15. Angiotensin-converting enzyme 2 (ACE2) changes over time [ Time Frame: 14 days ]
  16. Interleukin 6 (IL-6) changes over time [ Time Frame: 14 days ]
  17. Interleukin 8 (IL-8) changes over time [ Time Frame: 14 days ]
  18. Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time [ Time Frame: 14 days ]
  19. Plasminogen activator inhibitor type-1 (PAI-1) changes over time [ Time Frame: 14 days ]
  20. Von willebrand factor (vWF) changes over time [ Time Frame: 14 days ]
  21. Tumor necrosis factor-α (TNF-α) changes over time [ Time Frame: 14 days ]
  22. Soluble receptor for advanced glycation end products (sRAGE) changes over time [ Time Frame: 14 days ]
  23. Surfactant protein-D (SP-D) changes over time [ Time Frame: 14 days ]
  24. Angiopoietin-2 changes over time [ Time Frame: 14 days ]
  25. Frequency of adverse events and severe adverse events [ Time Frame: 14 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04287686


Locations
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China, Guangdong
GCP Office of The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China, 510120
Sponsors and Collaborators
The First Affiliated Hospital of Guangzhou Medical University
Investigators
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Principal Investigator: Yimin Li, PhD, MD The First Affiliated Hospital of Guangzhou Medical University
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Responsible Party: Yimin LI, Director Physician, The First Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT04287686    
Other Study ID Numbers: GIRH-APN01
First Posted: February 27, 2020    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yimin LI, The First Affiliated Hospital of Guangzhou Medical University:
SARS-CoV-2
Renin-angiotensin-system (RAS)