Ignite Creation Date:
2024-05-06 @ 2:26 PM
Last Modification Date:
2024-10-26 @ 1:30 PM
Study NCT ID:
NCT04311697
Status:
COMPLETED
Last Update Posted:
2023-07-24
First Post:
2020-03-14
Brief Title:
Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure
Sponsor:
APR Applied Pharma Research sa
Organization:
APR Applied Pharma Research sa
Study Overview
Official Title:
ZYESAMI Aviptadil for the Treatment of Critical COVID-19 With Respiratory Failure
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
True
If Expanded Access, NCT#:
NCT04453839
Has Expanded Access, NCT# Status:
NO_LONGER_AVAILABLE
Acronym:
COVID-AIV
Brief Summary:
Novel Corona Virus SARS-CoV-2 is known to cause Respiratory Failure which is the hallmark of Acute COVID-19 as defined by the new NIHFDA classification Approximately 50 of those who develop Critical COVID-19 die despite intensive care and mechanical ventilation Patients with Critical COVID-19 and respiratory failure currently treated with high flow nasal oxygen non-invasive ventilation or mechanical ventilation will be treated with ZYESAMI aviptadil a synthetic form of Human Vasoactive Intestinal Polypeptide VIP plus maximal intensive care vs placebo maximal intensive care Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmolkghr over 12 hours
Detailed Description:
Acute Lung Injury which triggers Critical COVID-19 is a known lethal complication of Corona Virus SARS-CoV-2 infection Conventional medical therapy including intensive care and respiratory support is associated with an 80 mortality Aviptadil a synthetic form of Human Vasoactive Intestinal Polypeptide VIP has been awarded FDA Orphan Drug Designation for the treatment of ARDS and admitted to the FDA CoronaVirus Technology Accelerator Program
VIP binds to VPAC1 receptors on the pulmonary Alveolar Type II ATII cell ATII cells comprise only 5 of lung epithelial cells but are critical for oxygen transfer surfactant production and maintenance of Alveolar Type 1 cells 70 of VIP binds to this receptor The Type II cell is also the cell selectively attacked by the SARS-CoV-2 virus via the ACE2 surface receptor
Nonclinical studies demonstrate that VIP is highly concentrated in the lung and specifically bound to the ATII cell where it prevents NMDA-induced caspase-3 activation in the lung inhibits IL6 and TNFa production protects against HCl-induced pulmonary edema and upregulates surfactant production These and other effects have been observed in numerous animal model systems of lung injury in mice rats guinea pigs sheep swine and dogs In these models Aviptadil restores barrier function at the endothelialalveolar interface and thereby protects the lung and other organs from failure
Aviptadil ihas a demonstrated 20 year history of safety in phase 2 trials for Sarcoid Pulmonary Fibrosis Bronchospasm and a phase I trial in ARDS In that phase I trial 8 patients with severe ARDS on mechanical ventilation were treated with ascending doses of VIP Seven of the 8 patients were successfully extubated and were alive at the five day timepoint Six left the hospital and one died of an unrelated cardiac event
Five phase 2 trials of aviptadil have been conducted under European regulatory authority Numerous healthy volunteer studies have shown that iv infusion of Aviptadil is well tolerated with few adverse effects including alterations in blood pressure heart rate or ECG In addition to published studies of human use Aviptadil has been used on a compounded basis in certain ICUs for many years in the belief that it preserves life and restores function in pulmonary hypertension ARDS and Acute Lung Injury ALI
In this study patients who are hospitalized for Critical COVID-19 infection with respiratory failure will be randomly allocated to Aviptadil administered by intravenous infusion in addition to maximal intensive care vs maximal intensive care alone Primary endpoints will be improvement in blood oxygenation and mortality
VIP binds to VPAC1 receptors on the pulmonary Alveolar Type II ATII cell ATII cells comprise only 5 of lung epithelial cells but are critical for oxygen transfer surfactant production and maintenance of Alveolar Type 1 cells 70 of VIP binds to this receptor The Type II cell is also the cell selectively attacked by the SARS-CoV-2 virus via the ACE2 surface receptor
Nonclinical studies demonstrate that VIP is highly concentrated in the lung and specifically bound to the ATII cell where it prevents NMDA-induced caspase-3 activation in the lung inhibits IL6 and TNFa production protects against HCl-induced pulmonary edema and upregulates surfactant production These and other effects have been observed in numerous animal model systems of lung injury in mice rats guinea pigs sheep swine and dogs In these models Aviptadil restores barrier function at the endothelialalveolar interface and thereby protects the lung and other organs from failure
Aviptadil ihas a demonstrated 20 year history of safety in phase 2 trials for Sarcoid Pulmonary Fibrosis Bronchospasm and a phase I trial in ARDS In that phase I trial 8 patients with severe ARDS on mechanical ventilation were treated with ascending doses of VIP Seven of the 8 patients were successfully extubated and were alive at the five day timepoint Six left the hospital and one died of an unrelated cardiac event
Five phase 2 trials of aviptadil have been conducted under European regulatory authority Numerous healthy volunteer studies have shown that iv infusion of Aviptadil is well tolerated with few adverse effects including alterations in blood pressure heart rate or ECG In addition to published studies of human use Aviptadil has been used on a compounded basis in certain ICUs for many years in the belief that it preserves life and restores function in pulmonary hypertension ARDS and Acute Lung Injury ALI
In this study patients who are hospitalized for Critical COVID-19 infection with respiratory failure will be randomly allocated to Aviptadil administered by intravenous infusion in addition to maximal intensive care vs maximal intensive care alone Primary endpoints will be improvement in blood oxygenation and mortality
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None