Ignite Creation Date:
2024-05-06 @ 2:36 PM
Last Modification Date:
2024-10-26 @ 1:33 PM
Study NCT ID:
NCT04360096
Status:
TERMINATED
Last Update Posted:
2023-02-03
First Post:
2020-04-21
Brief Title:
Inhaled ZYESAMI Aviptadil Acetate for the Treatment of Severe COVID-19
Sponsor:
APR Applied Pharma Research sa
Organization:
APR Applied Pharma Research sa
Study Overview
Official Title:
Inhaled ZYESAMI for the Treatment of Severe COVID-19
Status:
TERMINATED
Status Verified Date:
2021-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Sponsor decision
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AVICOVID-2
Brief Summary:
Brief Summary
SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation Mortality rates as high as 80 have been reported among those who require mechanical ventilation despite best available intensive care
Patients with severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized ZYESAMI aviptadil acetate a synthetic version of Vasoactive Intestinal Polypeptide VIP 100 μg 3x daily plus Standard of Care vs placebo Standard of Care using an FDA 501k cleared mesh nebulizer
The primary outcome will be progression in severity of COVID-19 ie critical OR severe progressing to critical over 28 days Secondary outcomes will include blood oxygenation as measured by pulse oximetry dyspnea exercise tolerance and levels of TNFα IL-6 and other cytokines
SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation Mortality rates as high as 80 have been reported among those who require mechanical ventilation despite best available intensive care
Patients with severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized ZYESAMI aviptadil acetate a synthetic version of Vasoactive Intestinal Polypeptide VIP 100 μg 3x daily plus Standard of Care vs placebo Standard of Care using an FDA 501k cleared mesh nebulizer
The primary outcome will be progression in severity of COVID-19 ie critical OR severe progressing to critical over 28 days Secondary outcomes will include blood oxygenation as measured by pulse oximetry dyspnea exercise tolerance and levels of TNFα IL-6 and other cytokines
Detailed Description:
Detailed Description
Attack of the Alveolar Type II ATII cell via its ACE2 surface receptor by the SARS-CoV-2 virus leads to respiratory failure morbidity and frequently mortality in COVID-19 There is no approved treatment that specifically targets the pulmonary injury Vasoactive Intestinal Peptide VIP is known to target the VPAC1 receptor of the ATII cell and to protect that cell against all manner of injuries including smoke inhalation exposure to stomach acid and exposure to infectious agents VIP prevents apoptosis blocks cytokines lowers TNFα levels reverses CD4CD8 ratio and reduces cough and dyspnea in nonclinical and clinical studies Aviptadil acetate a synthetic form of Vasoactive Intestinal Polypeptide VIP has been awarded FDA Orphan Drug Designation for the treatment of ARDS and Pulmonary Hypertension and EMEA Orphan Drug Designation for the treatment of ARDS and Sarcoid ZYESAMI Aviptadil has been granted FDA Fast Track Designation for the treatment of ARDSAcute Lung Injury in COVID-19
The objective of this study is to identify patients severe COVID-19 who have not yet developed respiratory failure and to treat them with inhaled ZYESAMI in the hope of preventing progression to Critical COVID-19 with Respiratory Failure
Nonclinical studies demonstrate that VIP is 70 concentrated in the lung where it binds primarily to ATII cells VIP prevents NMDA-induced caspase-3 activation in the lung inhibits IL6 and TNFα production protects against HCl-induced pulmonary edema 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
Both intravenous and inhalation preclinical toxicology and safety pharmacology have been performed in four species with a six-month trial of inhaled Aviptadil in primates
Aviptadil is approved for human use in the treatment of erectile dysfunction in Scandinavia and several European countries in co-formulation with phentolamine and has a demonstrated phase 2 safety in trials for Sarcoid Pulmonary Fibrosis and Bronchospasm No adverse safety signals were seen in a phase I trial IV Aviptadil 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
A 60-day phase 2b3 trial of IV Aviptadil NCT 04311697 has recently completed enrollment and 28-day top-line safety data have been reported No unanticipated serious adverse events were reported The only adverse event that was statistically more frequent in Aviptadil-treated participants than among placebo-treated participants was mild to moderate diarrhea which has not been reported as a frequent side-effect of inhaled Aviptadil 30 vs 15 p 001 Systemic hypotension was seen in both Aviptadil-treated and placebo-treated participants 25 vs 185 PNS
Five GCP phase 2 trials of Aviptadil were conducted under European regulatory authority Non GCP 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 with severe COVID-19 by FDA definition who have not developed respiratory failure will be treated with nebulized ZYESAMI 100 μg in 1 cc normal saline 3x daily plus Standard of Care vs placebo Standard of Care using an FDA 501k cleared mesh nebulizer
The primary outcome will be progression to in severity of COVID-19 ie critical OR severe progressing to critical over 28 days Secondary outcomes will include blood oxygenation as measured by pulse oximetry dyspnea exercise tolerance and levels of TNFα IL-6 and other cytokines
Attack of the Alveolar Type II ATII cell via its ACE2 surface receptor by the SARS-CoV-2 virus leads to respiratory failure morbidity and frequently mortality in COVID-19 There is no approved treatment that specifically targets the pulmonary injury Vasoactive Intestinal Peptide VIP is known to target the VPAC1 receptor of the ATII cell and to protect that cell against all manner of injuries including smoke inhalation exposure to stomach acid and exposure to infectious agents VIP prevents apoptosis blocks cytokines lowers TNFα levels reverses CD4CD8 ratio and reduces cough and dyspnea in nonclinical and clinical studies Aviptadil acetate a synthetic form of Vasoactive Intestinal Polypeptide VIP has been awarded FDA Orphan Drug Designation for the treatment of ARDS and Pulmonary Hypertension and EMEA Orphan Drug Designation for the treatment of ARDS and Sarcoid ZYESAMI Aviptadil has been granted FDA Fast Track Designation for the treatment of ARDSAcute Lung Injury in COVID-19
The objective of this study is to identify patients severe COVID-19 who have not yet developed respiratory failure and to treat them with inhaled ZYESAMI in the hope of preventing progression to Critical COVID-19 with Respiratory Failure
Nonclinical studies demonstrate that VIP is 70 concentrated in the lung where it binds primarily to ATII cells VIP prevents NMDA-induced caspase-3 activation in the lung inhibits IL6 and TNFα production protects against HCl-induced pulmonary edema 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
Both intravenous and inhalation preclinical toxicology and safety pharmacology have been performed in four species with a six-month trial of inhaled Aviptadil in primates
Aviptadil is approved for human use in the treatment of erectile dysfunction in Scandinavia and several European countries in co-formulation with phentolamine and has a demonstrated phase 2 safety in trials for Sarcoid Pulmonary Fibrosis and Bronchospasm No adverse safety signals were seen in a phase I trial IV Aviptadil 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
A 60-day phase 2b3 trial of IV Aviptadil NCT 04311697 has recently completed enrollment and 28-day top-line safety data have been reported No unanticipated serious adverse events were reported The only adverse event that was statistically more frequent in Aviptadil-treated participants than among placebo-treated participants was mild to moderate diarrhea which has not been reported as a frequent side-effect of inhaled Aviptadil 30 vs 15 p 001 Systemic hypotension was seen in both Aviptadil-treated and placebo-treated participants 25 vs 185 PNS
Five GCP phase 2 trials of Aviptadil were conducted under European regulatory authority Non GCP 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 with severe COVID-19 by FDA definition who have not developed respiratory failure will be treated with nebulized ZYESAMI 100 μg in 1 cc normal saline 3x daily plus Standard of Care vs placebo Standard of Care using an FDA 501k cleared mesh nebulizer
The primary outcome will be progression to in severity of COVID-19 ie critical OR severe progressing to critical over 28 days Secondary outcomes will include blood oxygenation as measured by pulse oximetry dyspnea exercise tolerance and levels of TNFα IL-6 and other cytokines
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None