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Inhaled ZYESAMI™ (Aviptadil Acetate) for the Treatment of Severe COVID-19 (AVICOVID-2)

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ClinicalTrials.gov Identifier: NCT04360096
Recruitment Status : Recruiting
First Posted : April 24, 2020
Last Update Posted : June 10, 2021
Sponsor:
Information provided by (Responsible Party):
NeuroRx, Inc.

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.


Condition or disease Intervention/treatment Phase
SARS-CoV 2 COVID ARDS ALI Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Dyspnea Drug: ZYESAMI™ (aviptadil acetate) Drug: Placebo Device: Nebulized administration of ZYESAMI™ or Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter Randomized Placebo-controlled Trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Only the study pharmacist will be aware of treatment assignment
Primary Purpose: Treatment
Official Title: Inhaled ZYESAMI™ for the Treatment of Severe COVID-19
Actual Study Start Date : February 15, 2021
Estimated Primary Completion Date : August 15, 2021
Estimated Study Completion Date : September 1, 2021


Arm Intervention/treatment
Experimental: Severe COVID-19 ZYESAMI™
Patients with Severe COVID-19 to be treated with inhaled ZYESAMI™ (aviptadil) by mesh nebulizer 100μg 3x daily
Drug: ZYESAMI™ (aviptadil acetate)
Inhaled ZYESAMI™ (aviptadil acetate) 100μg 3x daily by mesh nebulizer

Device: Nebulized administration of ZYESAMI™ or Placebo
Use of 510(k) cleared mesh nebulizer to deliver investigational product

Experimental: Severe COVID-19 Placebo
Patients with Severe COVID-19 to be treated with inhaled placebo 3x daily
Drug: Placebo
Normal Saline Inhalation

Device: Nebulized administration of ZYESAMI™ or Placebo
Use of 510(k) cleared mesh nebulizer to deliver investigational product




Primary Outcome Measures :
  1. Progression to Respiratory Failure [ Time Frame: 28 days ]
    Progression to Respiratory Failure is defined as the need for mechanical ventilation, non-invasive ventilation or high flow nasal oxygen


Secondary Outcome Measures :
  1. Blood oxygenation [ Time Frame: 28 days ]
    Blood PO2 as measured by pulse oximetry

  2. RPD Dyspnea Scale [ Time Frame: 28 days ]

    0 = no shortness of breath at all 0.5 = very, very slight shortness of breath

    1. = very mild shortness of breath
    2. = mild shortness of breath
    3. = moderate shortness of breath or breathing difficulty
    4. = somewhat severe shortness of breath
    5. = strong or hard breathing

    7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity


  3. Distance walked in six minutes [ Time Frame: 28 days ]
    Distance walked in six minutes



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. 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

  2. Positive test by standard RT-PCR assay or equivalent within last 7 days
  3. 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

Exclusion criteria:

  1. Evidence of Critical COVID-19
  2. Inability to utilize nebulized drugs, or history of bronchospasm with inhaled medications
  3. Age <12 years;
  4. Mean arterial pressure < 65 mm Hg after initial hospital stabilization,
  5. Non-COVID-19 irreversible underlying condition with projected fatal course within 6 months or with high risk of mortality;
  6. Immunosuppressive treatment for transplant or other diseases associated with high mortality;
  7. 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
  8. Myocardial Infarction in previous six months or troponin >0.5
  9. Recent history of venous thrombotic events (PE / DVT) within the last 3 months.
  10. 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
  11. Watery diarrhea requiring replacement of 1 liter or more of iv fluids and electrolytes
  12. Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04360096


Contacts
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Contact: Robert E Besthof, MIM +48425461134 rbesthof@neurorxpharma.com

Locations
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United States, California
St. Jude Medical Center Recruiting
Fullerton, California, United States, 92835
Contact: Linda Gozar       Linda.Gozar@stjoe.org   
Principal Investigator: David Park, MD         
University of California - Irvine Recruiting
Irvine, California, United States, 92697
Contact: Rosie Magallon       rmagallo@hs.uci.edu   
Principal Investigator: Richard Lee, MD         
United States, Florida
University of Miami Leonard M. Miller School of Medicine (UMMSM) Recruiting
Miami, Florida, United States, 33136
Contact: Mayra Vidro    305-243-7047    mvidro@med.miami.edu   
Contact: Russell Saltzman    305 243 1152    r.saltzman@med.miami.edu   
Principal Investigator: Dushyantha Jayaweera, MD         
United States, Illinois
Northwestern Medical Group Recruiting
Winfield, Illinois, United States, 60190
Contact: Sarah Madia    630-933-5281    sarah.madia@nm.org   
Principal Investigator: Luis Manrique, MD         
United States, Kentucky
University of Louisville Hospital Recruiting
Louisville, Kentucky, United States, 40202
Contact: Elizabeth Cooke       Elizabetha.cooke@louisville.edu   
Principal Investigator: Rainer Lenhardt, MD         
United States, Pennsylvania
Doylestown Hospital Recruiting
Doylestown, Pennsylvania, United States, 18901
Contact: Teresa Mannion    215-345-2842    tmannion@dh.org   
Principal Investigator: Les Szekely, MD         
United States, Texas
University of Texas San Antonio Medical Arts and Research Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Robin Tragus    210-567-5262    tragus@uthscsa.edu   
Principal Investigator: Thomas Patterson, MD         
Sponsors and Collaborators
NeuroRx, Inc.
Investigators
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Study Chair: Jonathan C Javitt, MD, MPH NeuroRx
Additional Information:
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Responsible Party: NeuroRx, Inc.
ClinicalTrials.gov Identifier: NCT04360096    
Other Study ID Numbers: RLF-100_002
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by NeuroRx, Inc.:
Corona Virus
VIP
Aviptadil
Vasoactive Intestinal Polypeptide
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Dyspnea
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Signs and Symptoms, Respiratory
Thoracic Injuries
Wounds and Injuries