Clinical trial NCT04287686: Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients With COVID-19
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: COVID-19
Keywords: SARS-CoV-2
Renin-angiotensin-system (RAS)
Lead sponsor: The First Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2020-02-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-arm pilot study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time course of body temperature (fever)
timeFrame: 14 days
measure: Viral load over time
timeFrame: 14 days
Secondary outcomes:
measure: P/F ratio over time
timeFrame: 14 days
measure: Sequential organ failure assessment score(SOFA score) over time
timeFrame: 14 days
measure: Pulmonary Severity Index (PSI)
timeFrame: 14 days
measure: Image examination of chest over time
timeFrame: 14 days
measure: Proportion of subjects who progressed to critical illness or death
timeFrame: 14 days
measure: Time from first dose to conversion to normal or mild pneumonia
timeFrame: 14 days
measure: T-lymphocyte counts over time
timeFrame: 14 days
measure: C-reactive protein levels over time
timeFrame: 14 days
measure: Angiotensin II (Ang II) changes over time
timeFrame: 14 days
measure: Angiotensin 1-7 (Ang 1-7) changes over time
timeFrame: 14 days
measure: Angiotensin 1-5 (Ang 1-5) changes over time
timeFrame: 14 days
measure: Renin changes over time
timeFrame: 14 days
measure: Aldosterone changes over time
timeFrame: 14 days
measure: Angiotensin-converting enzyme (ACE) changes over time
timeFrame: 14 days
measure: Angiotensin-converting enzyme 2 (ACE2) changes over time
timeFrame: 14 days
measure: Interleukin 6 (IL-6) changes over time
timeFrame: 14 days
measure: Interleukin 8 (IL-8) changes over time
timeFrame: 14 days
measure: Soluble tumor necrosis factor receptor type II (sTNFrII) changes over time
timeFrame: 14 days
measure: Plasminogen activator inhibitor type-1 (PAI-1) changes over time
timeFrame: 14 days
measure: Von willebrand factor (vWF) changes over time
timeFrame: 14 days
measure: Tumor necrosis factor-α (TNF-α) changes over time
timeFrame: 14 days
measure: Soluble receptor for advanced glycation end products (sRAGE) changes over time
timeFrame: 14 days
measure: Surfactant protein-D (SP-D) changes over time
timeFrame: 14 days
measure: Angiopoietin-2 changes over time
timeFrame: 14 days
measure: Frequency of adverse events and severe adverse events
timeFrame: 14 days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: GCP Office of The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Yimin Li, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.