ZYESAMI (Aviptadil) Intermediate Population Expanded Access Protocol (SAMICARE)
NCT ID: NCT04453839
Last Updated: 2023-02-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NO_LONGER_AVAILABLE
EXPANDED_ACCESS
Brief Summary
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Treating physicians must complete FDA Form 3396 and receive a letter of authorization from NeuroRx, along with local IRB authorization.
Please refer to FDA guidance for Individual Patient Expanded Access https://www.fda.gov/media/91160/download
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Detailed Description
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5.1 Executive Summary ZYESAMI (aviptadil) is a synthetic form of Vasoactive Intestinal Polypeptide (VIP), a ubiquitous, naturally synthesized human peptide with extensively documented anti-inflammatory, anti-cytokine cascade properties. It has been granted FDA Fast Track Designation for treatment of Critical COVID-19 with Respiratory Failure. A phase 2/3 trial is underway that has passed its first evaluation at 30 patients for safety and futility. This expanded access protocol is designed to offer access to investigational use of RLF-100 to patients who do not qualify for inclusion in Protocol RLF-100-001 (NCT04311697) either on the basis of specific medical exclusions or because there is no accessible study site available to the prospective participant.
5.2 Definition of Critical COVID-19
In May 2020, FDA defined Critical COVID-19 to be used in clinical trials and disease staging as follows:
Critical COVID-19
* Positive testing by standard RT-PCR assay or an equivalent test
* Evidence of Respiratory Failure based on FDA definition of: need for Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \> 20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation)
Acute Lung Injury in COVID-19 is characterized by progressive failure of corporeal oxygenation, attributed on large part by SARS-CoV-2 infection of Alveolar Type II cells (Mason 2020). Extensive nonclinical studies document that 70% of VIP in the body binds to receptors on the Alveolar Type II cell, where VIP is known to block cytokine production and upregulate production of surfactant.
Severity of COVID is associated with and graded by a progressively worsened state of oxygenation. This is seen in the PaO2/FIO2 ratio, which reflects the status of oxygenation for patients on high pressure oxygen and mechanical ventilation. In patients breathing room air, disease severity is assessed by SpO2. Many patients with Critical COVID meet the clinical definitions of Acute Respiratory Distress Syndrome (ARDS). However, there is increasing recognition that respiratory distress in COVID-19 has different characteristics than ARDS in the setting of bacterial sepsis and other common presentations of ARDS.
The pathologic hallmark of COVID-19 lung injury is diffuse alveolar damage, vascular endothelium damage, and damage to the surfactant-producing type II cells which results in loss of the integrity of the alveolar-capillary barrier, transudation of protein-rich fluid across the barrier, pulmonary edema, and hypoxemia from intrapulmonary shunting. Typically, patients who have progressed to Critical COVID-19 require care in an intensive care unit (ICU). The mortality rate is approximately 50%. Deaths usually result from multisystem organ failure rather than lung failure alone.
5.3 ZYESAMI Experimental Therapy in COVID-19
Under this protocol, patients with Critical COVID-19 will be treated with ZYESAMI (Aviptadil) with the aim to support pulmonary alveolar function, combat the cytokine-induced inflammation, improve blood oxygenation, and reduce mortality.
5.4 Clinical Rationale Given by intravenous infusion in appropriate concentrations, ZYESAMI has been shown in clinical trials to have a manageable safety profile with no observed SAEs to date that would rise to the level of a black box warning.
6\. OBJECTIVES
6.1 Primary Objective The primary objective of this study is to measure the effectiveness and safety of ZYESAMI + maximal standard of care (SOC) in treating Critical COVID-19 with Respiratory Failure.
6.2 Secondary Objective The key secondary objective is to test the hypothesis that ZYESAMI improves blood oxygenation as measured by SaO2.
Conditions
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Interventions
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ZYESAMI (aviptadil acetate)
Patients will be treated with 12 hour infusions of ZYESAMI at ascending doses of 50/100/150 pmol/kg/hr on 3 or more successive days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Mean Arterial Pressure \< 65 mm Hg with use of pressor per ICU protocol
* Irreversible condition (other than COVID-19) with projected fatal course
* ECMO
* Chemotherapy-induced neutropenia (granulocyte count \<1000/mm3);
* Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4;
* Liquid Diarrhea more than 3x/day; defined as more than 3 non-bloody watery stools within a 24-hour period, requiring additional fluid and electrolyte supplementation
12 Years
100 Years
ALL
No
Sponsors
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APR Applied Pharma Research s.a.
OTHER
Responsible Party
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Principal Investigators
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Jonathan C Javitt, MD, MPH
Role: STUDY_CHAIR
NRx Pharmaceuticals, Inc.
Locations
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Dignity Health-Mercy Gilbert Medical Center
Gilbert, Arizona, United States
Honor Health Shea Medical Center
Scottsdale, Arizona, United States
Kaiser Permanente
Baldwin Park, California, United States
University of California - Irvine
Irvine, California, United States
Lawnwood Regional Medical Center
Ft. Pierce, Florida, United States
Lakeland Regional Health
Lakeland, Florida, United States
Miller School of Medicine / University of Miami Medical Center
Miami, Florida, United States
Baptist Hospital of Miami
Miami, Florida, United States
Baycare St. Joseph Hospital
Tampa, Florida, United States
Southeast Georgia Health system
Brunswick, Georgia, United States
Maui Health Systems
Wailuku, Hawaii, United States
St. Anthony Regional Hospital
Carroll, Iowa, United States
University of Louisville
Louisville, Kentucky, United States
St. Tammany Parish Hospital
Covington, Louisiana, United States
Our Ladies of Lourdes Regional Hospital
Lafayette, Louisiana, United States
St. Joseph Heritage Healthcare
Saint Joseph, Missouri, United States
Great Plains Health
North Platte, Nebraska, United States
Self Regional Healthcare
Greenwood, South Carolina, United States
Hendrick Medical Center
Abilene, Texas, United States
Baptist Hospitals of Southeast Texas
Beaumont, Texas, United States
Medical City Denton
Denton, Texas, United States
HR Health Institute for Research & Development
Edinburg, Texas, United States
Houston Methodist Hospital
Houston, Texas, United States
Memorial Hermann Hospital Houston
Houston, Texas, United States
Medical City McKinney
McKinney, Texas, United States
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Informed Consent Form
Related Links
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Intravenous Aviptadil Is Associated with Increased Recovery and Survival in Patients with COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial
Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide
Other Identifiers
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ZYESAMI_EA-1
Identifier Type: -
Identifier Source: org_study_id
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