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

NCT05137795 | Withdrawn Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: Zyesami_003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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; Zyesami

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

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

  NRx Pharmaceuticals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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
• Expanded Access: Yes

Model Details: Multicenter Randomized Placebo-controlled Trial

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: November 30, 2021
• Study Start: December 15, 2021
• Primary Completion: June 15, 2022
• Study Completion: August 15, 2022
• Last Updated: February 3, 2023

Record last verified: 2022-07