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

NCT ID: NCT04287686

Last Updated: 2020-03-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-29
• Study Completion Date: 2020-04-30

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rhACE2 group

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

Group Type: EXPERIMENTAL

Recombinant human angiotensin-converting enzyme 2 (rhACE2)

Intervention Type: DRUG

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Yimin LI

Director Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yimin Li, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Guangzhou Medical University

Locations

GCP Office of The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 32522846 (View on PubMed)

Other Identifiers

GIRH-APN01

Identifier Type: -

Identifier Source: org_study_id