Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure

NCT04311697 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: COVID-AIV
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 10

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 NIH/FDA 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 pmol/kg/hr over 12 hours.

Conditions

Critical COVID-19 With Respiratory Failure; Acute Respiratory Distress Syndrome (ARDS); Corona Virus Infection; Acute Lung Injury

Keywords

COVID-19; ARDS; Aviptadil; Acute Respiratory Distress Syndrome; Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• Resolution of Respiratory Failure (Alive and Free of Respiratory Failure)

  Participant is Alive and Free of Respiratory Failure (without subsequent relapse over 7 days) determined as no longer requiring acute care or more than low flow oxygen

  Day 28

Secondary Outcomes (3)

• Number of Participants Alive at Day 60

  Day 60

• Number of Participants Achieving a Score of 6-8 on NIAID Ordinal Score Through Day 60

  Day 60

• Oxygenation Index as Measured by PaO2:FiO2 Ratio

  Day 7

Other Outcomes (1)

• Change in IL-6

  Day 28

Study Arms (2)

Aviptadil IV in escalating doses + standard of care

EXPERIMENTAL

Patients will be administered Aviptadil IV in escalating doses of 50 pmol, 100 pmol, 150 pmol/kg/hr

Drug: Aviptadil by intravenous infusion + standard of care

Placebo + standard of care

EXPERIMENTAL

Patients will first be treated with placebo infusion + maximal intensive care

Drug: Normal Saline Infusion + standard of care

Interventions

Aviptadil by intravenous infusion + standard of care DRUG

Aviptadil by intravenous infusion + standard of care (SOC). SOC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures.

Also known as: ZYESAMI (aviptadil) +SOC

Aviptadil IV in escalating doses + standard of care

Normal Saline Infusion + standard of care DRUG

Saline by intravenous infusion + standard of care (SOC). SOC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures.

Also known as: Placebo+SOC

Placebo + standard of care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Critical COVID-19 with respiratory failure
• Physician determination that patient is on maximal conventional medical therapy

You may not qualify if:

• Pregnancy (pregnant women may apply for open label treatment under compassionate care IND
• Age \<18 years
• Mechanical ventilation for more than 7 days in primary cohort. Mechanical ventilation\>21 days in the exploratory cohort
• Mean Arterial Pressure \< 65 mm Hg with use of pressor per ICU protocol
• Irreversible condition (other than COVID-19) with projected fatal course
• ECMO
• Current or recent (within 30 d) enrollment in another investigational trial of anti-IL6 drug;
• Active diagnosis of Acquired immune deficiency syndrome;
• Transplant patients currently immunosuppressed;
• Chemotherapy-induced neutropenia (granulocyte count \<1000/mm3);
• Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4;
• Recent myocardial infarction - within last 6 months and troponin \> 0.5
• Anuria (urine output \< 50 ml/d) or other signs of multi-organ failure
• Severe liver disease with portal hypertension;
• Recent stroke or head trauma within last 12 months

Sponsors & Collaborators

• APR Applied Pharma Research s.a.: lead

Study Sites (10)

St. Jude Medical Center

Fullerton, California, 92835, United States

Location

University of California - Irvine

Irvine, California, 92697, United States

Location

Miller School of Medicine / University of Miami Medical Center

Miami, Florida, 33136, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Heartland/Mosaic Health

Saint Joseph, Missouri, 64506, United States

Location

Hendrick Health

Abilene, Texas, 79601, United States

Location

Texas Health Harris Methodist Hospital

Fort Worth, Texas, 76104, United States

Location

Texas Health Hospital Frisco

Frisco, Texas, 75033, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Youssef JG, Lavin P, Schoenfeld DA, Lee RA, Lenhardt R, Park DJ, Fernandez JP, Morganroth ML, Javitt JC, Jayaweera D. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Crit Care Med. 2022 Nov 1;50(11):1545-1554. doi: 10.1097/CCM.0000000000005660. Epub 2022 Aug 29.

  PMID: 36044317 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Coronavirus Infections; Acute Lung Injury; COVID-19; Respiratory Insufficiency

Interventions

Standard of Care; aviptadil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Lung Injury; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Paola Prina
• Organization: Applied Pharma Rersearch

paola.prina@apr.ch

4847169881

Study Officials

• Jonathan C Javitt, MD, MPH

  NeuroRx, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized, placebo-controlled trial with identical drug and placebo infusion bags
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Multicenter trial, initially conducted at a single center with a safety/futility assessment following enrollment of 30 patients, expanded to 196 total patients at 12 study sites

Study Record Dates

• First Submitted: March 14, 2020
• First Posted: March 17, 2020
• Study Start: May 15, 2020
• Primary Completion: February 22, 2021
• Study Completion: February 22, 2021
• Last Updated: July 24, 2023
• Results First Posted: July 24, 2023

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Currently available
• Access Criteria: Public access

Locations

US (10)