Inhaled ZYESAMI™ (Aviptadil Acetate) for the Treatment of Severe COVID-19

NCT04360096 | Terminated Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: RLF-100_002
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 13

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 501(k) cleared mesh nebulizer. The primary outcome will be progression in severity of COVID-19 (i.e. 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.

Conditions

SARS-CoV 2; COVID; ARDS; ALI; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Dyspnea

Keywords

Corona Virus; VIP; Aviptadil; Vasoactive Intestinal Polypeptide

Outcome Measures

Primary Outcomes (1)

• Progression to Respiratory Failure

  Progression to Respiratory Failure is defined as the need for mechanical ventilation, non-invasive ventilation or high flow nasal oxygen

  28 days

Secondary Outcomes (3)

• Blood oxygenation

  28 days

• RPD Dyspnea Scale

  28 days

• Distance walked in six minutes

  28 days

Study Arms (2)

Severe COVID-19 ZYESAMI™

EXPERIMENTAL

Patients with Severe COVID-19 to be treated with inhaled ZYESAMI™ (aviptadil) by mesh nebulizer 100μg 3x daily

Drug: ZYESAMI™ (aviptadil acetate); Device: Nebulized administration of ZYESAMI™ or Placebo

Severe COVID-19 Placebo

EXPERIMENTAL

Patients with Severe COVID-19 to be treated with inhaled placebo 3x daily

Drug: Placebo; Device: Nebulized administration of ZYESAMI™ or Placebo

Interventions

ZYESAMI™ (aviptadil acetate) DRUG

Inhaled ZYESAMI™ (aviptadil acetate) 100μg 3x daily by mesh nebulizer

Severe COVID-19 ZYESAMI™

Placebo DRUG

Normal Saline Inhalation

Severe COVID-19 Placebo

Nebulized administration of ZYESAMI™ or Placebo DEVICE

Use of 510(k) cleared mesh nebulizer to deliver investigational product

Severe COVID-19 Placebo; Severe COVID-19 ZYESAMI™

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe COVID-19 , as defined by clinical signs indicative of severe systemic illness with COVID-19, being given oxygenation and meeting
• ONE of the following:
• Respiratory rate ≥ 30 per minute Heart rate ≥ 125 per minute SpO2 ≤ 93% on room air at sea level PaO2/FiO2 \< 300 mmHg or SpO2/FiO2 \< 315 mmHg
• Positive test by standard RT-PCR assay or equivalent within last 7 days
• Physician determination that patient is on SOC therapy, and will receive standard of care if patient progresses to Critical COVID-19, patient must be full CODE

You may not qualify if:

• Evidence of Critical COVID-19
• Inability to utilize nebulized drugs, or history of bronchospasm with inhaled medications
• Age \<12 years;
• Mean arterial pressure \< 65 mm Hg after initial hospital stabilization,
• Non-COVID-19 irreversible underlying condition with projected fatal course within 6 months or with high risk of mortality;
• Immunosuppressive treatment for transplant or other diseases associated with high mortality;
• Stage IV cancer or cancer on active treatment with chemotherapy immunotherapy or checkpoint inhibitors; acute renal failure or chronic renal insufficiency with GFR less than 30; CHF New York Heart Association class III or IV, new neurologic disorder in the last 3 months or chronic neurologic disorder or other that would impact on assessing the resolution of severe COVID-19 respiratory failure
• Myocardial Infarction in previous six months or troponin \>0.5
• Recent history of venous thrombotic events (PE / DVT) within the last 3 months.
• New diagnosis of atrial fibrillation within the last 3 months. Acceptable if greater than 3 months and well controlled in the opinion of the investigator
• Watery diarrhea requiring replacement of 1 liter or more of iv fluids and electrolytes
• Pregnancy

Sponsors & Collaborators

• APR Applied Pharma Research s.a.: lead

Study Sites (13)

St. Jude Medical Center

Fullerton, California, 92835, United States

Location

University of California - Irvine

Irvine, California, 92697, United States

Location

University of Miami Leonard M. Miller School of Medicine (UMMSM)

Miami, Florida, 33136, United States

Location

Advent Health Research Institute

Orlando, Florida, 32803, United States

Location

Northwestern Medical Group

Winfield, Illinois, 60190, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Great Plains Health

North Platte, Nebraska, 69101, United States

Location

University Medical Center

Las Vegas, Nevada, 89102, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

Kettering Health Network

Kettering, Ohio, 45429, United States

Location

Doylestown Hospital

Doylestown, Pennsylvania, 18901, United States

Location

Self Regional Healthcare

Greenwood, South Carolina, 29646, United States

Location

University of Texas San Antonio Medical Arts and Research Center

San Antonio, Texas, 78229, United States

Location

Related Links

• Pathogenesis of COVID-19 from a cell biologic perspective

MeSH Terms

Conditions

Acute Lung Injury; Respiratory Distress Syndrome; Dyspnea

Interventions

aviptadil

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jonathan C Javitt, MD, MPH

  NeuroRx

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the study pharmacist will be aware of treatment assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter Randomized Placebo-controlled Trial

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 24, 2020
• Study Start: February 15, 2021
• Primary Completion: December 15, 2021
• Study Completion: December 31, 2021
• Last Updated: February 3, 2023

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (13)