Inhaled Aviptadil for the Treatment of COVID-19 in Patients at High Risk for ARDS

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: 80

Summary

Conditions

ARDS
Aviptadil
Corona Virus Infection
COVID-19

Type

Interventional

Phase

Phase 2

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Patients will be randomly allocated to receive either Aviptadil together with standard care or the placebo (NaCl 0.9%) together with standard care,Masking: Double (Participant, Investigator)Masking Description: Patients and the investigator administering inhalation devices of drug or placebo are not aware of which group they have been randomized to (double-blinded). Someone not involved in the study (e.g. the hospital pharmacist or a nurse not involved in study) prepares the inhalation devices with either drug or placebo according to the randomization plan received by the CTUPrimary Purpose: Treatment

Participation Requirements

Age: Between 18 years and 125 years
Gender: Both males and females

Description

About 20% of individuals with Corona Virus disease (COVID-19) experience more severe disease characterized by significant respiratory symptoms including acute respiratory distress syndrome (ARDS). ARDS is a known lethal complication due to its low blood oxygenation levels and may result in organ failure. Until now, there are no specific vaccines or therapeutic drugs targeting SARS-CoV-2, alternative therapeutic interventions are needed to prevent and ameliorate respiratory conditions associated with COVID-19 to effectively reduce mortality and prevent ICU admissions. Aviptadil, which is a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP), might be beneficial in patients at risk of developing ARDS. Nonclinical studies demonstrate that VIP is highly concentrated in the lung, where it prevents N-methyl-D-aspartate (NMDA)-induced caspase-3 activation, inhibits IL-6 and TNFa production and protects against HCl-induced pulmonary edema. Further, in animal model systems of lung injury in mice, rats, guinea pigs, sheep, swine and dogs, Aviptadil was shown to restore barrier function at the endothelial/alveolar interface and to protect the lung and other organs from failure. In Europe, Aviptadil is approved for human use and has been shown to be safe in phase II trials for sarcoidosis, pulmonary fibrosis, bronchospasm, erectile dysfunction as well as in a phase I trial in ARDS in the past two decades. In the US, VIP has been given FDA Orphan Drug Designation for the treatment of ARDS and was admitted to the FDA Corona Virus Technology Accelerator Program. In a phase I trial of Aviptadil performed by Sami Said in the early 2000s, eight patients with severe ARDS on mechanical ventilation were treated with ascending doses of intravenous VIP. Seven patients (88%) were successfully extubated and were alive at the five day time point. Six (75%) left the hospital and one (13%) died of an unrelated cardiac event. A phase II clinical trial using intravenous Aviptadil in patients with COVID-19 infection and ARDS has begun. Further, a phase II/III clinical trial will study the effect of inhaled Aviptadil for the treatment of non-acute lung injury in COVID- 19 and begins in June 2020. In Europe, two phase II trials of Aviptadil have been conducted. Further, studies with healthy volunteers have shown that inhaled Aviptadil is well tolerated with few adverse effects.

Tracking Information

NCT #: NCT04536350
Collaborators: Not Provided
Investigators: Principal Investigator: Jörg D Leuppi, Professor Kantonsspital Baselland