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

Guangzhou Medical University

Status

Withdrawn

Conditions

COVID-19

Treatments

Drug: Recombinant human angiotensin-converting enzyme 2 (rhACE2)

Study type

Interventional

Funder types

Other

Identifiers

NCT04287686

GIRH-APN01

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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