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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04287686
• Other study ID #: GIRH-APN01
• Status: Withdrawn
• Phase: N/A
• Start date: February 2020
• Est. completion date: April 2020

Study information

• Verified date: March 2020
• Source: The First Affiliated Hospital of Guangzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

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.

Locations

Country	Name	City	State
China	GCP Office of The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time course of body temperature (fever)	Compare the time course of body temperature (fever) between two groups over time.	14 days
Primary	Viral load over time	Compare viral load between two groups over time.	14 days
Secondary	P/F ratio over time	PaO2/FiO2 ratio	14 days
Secondary	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.	14 days
Secondary	Pulmonary Severity Index (PSI)		14 days
Secondary	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.	14 days
Secondary	Proportion of subjects who progressed to critical illness or death		14 days
Secondary	Time from first dose to conversion to normal or mild pneumonia		14 days
Secondary	T-lymphocyte counts over time		14 days
Secondary	C-reactive protein levels over time		14 days
Secondary	Angiotensin II (Ang II) changes over time		14 days
Secondary	Angiotensin 1-7 (Ang 1-7) changes over time		14 days
Secondary	Angiotensin 1-5 (Ang 1-5) changes over time		14 days
Secondary	Renin changes over time		14 days
Secondary	Aldosterone changes over time		14 days
Secondary	Angiotensin-converting enzyme (ACE) changes over time		14 days
Secondary	Angiotensin-converting enzyme 2 (ACE2) changes over time		14 days
Secondary	Interleukin 6 (IL-6) changes over time		14 days
Secondary	Interleukin 8 (IL-8) changes over time		14 days
Secondary	Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time		14 days
Secondary	Plasminogen activator inhibitor type-1 (PAI-1) changes over time		14 days
Secondary	Von willebrand factor (vWF) changes over time		14 days
Secondary	Tumor necrosis factor-a (TNF-a) changes over time		14 days
Secondary	Soluble receptor for advanced glycation end products (sRAGE) changes over time		14 days
Secondary	Surfactant protein-D (SP-D) changes over time		14 days
Secondary	Angiopoietin-2 changes over time		14 days
Secondary	Frequency of adverse events and severe adverse events		14 days