ClinicalTrials.gov

History of Changes for Study: NCT04360096
Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19 (AVICOVID-2)
Latest version (submitted June 25, 2020) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 April 22, 2020 None (earliest Version on record)
2 June 25, 2020 Arms and Interventions, Eligibility, Study Status, Study Identification, Study Description, References, Study Design and Oversight
Comparison Format:

Scroll up to access the controls

Changes (Merged) for Study: NCT04360096
April 22, 2020 (v1) -- June 25, 2020 (v2)

Changes in: Arms and Interventions, Eligibility, Study Status, Study Identification, Study Description, References, Study Design and Oversight

Study Identification
Unique Protocol ID: RLF-100_002
Brief Title: Inhaled Aviptadil for the Treatment of Non-Acute Lung Injury in Moderate and Severe COVID-19 ( AVINALI AVICOVID-2)
Official Title: Inhaled Aviptadil for the Treatment of Non-Acute Lung Injury in Moderate and Severe COVID-19
Secondary IDs:
Study Status
Record Verification: April 2020
Overall Status: Not yet recruiting
Study Start: June July 1, 2020
Primary Completion: August October 1, 2020 [Anticipated]
Study Completion: October 1 November 30, 2020 [Anticipated]
First Submitted: April 21, 2020
First Submitted that
Met QC Criteria:
April 22, 2020
First Posted: April 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
April 22, 2020 June 25, 2020
Last Update Posted: April 24 June 29, 2020 [Actual]
Sponsor/Collaborators
Sponsor: NeuroRx, Inc.
Responsible Party: Sponsor
Collaborators:
Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No Yes
Unapproved/Uncleared Device:
Pediatric Postmarket Surveillance:
Data Monitoring: Yes
Study Description
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 Acute Critical COVID-19 with Respiratory Distress Syndrome Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who develop ARDS require mechanical ventilation, despite best available intensive care and mechanical ventilation .

Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, 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.

Patients with COVID-19 induced non-Acute Lung Injury who have demonstrated reduction in blood oxygenation, dyspnea, and exercise intolerance but do not require endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP) plus Standard of Care vs. placebo + Standard of Care. Patients will be randomized to intravenous Aviptadil will receive inhaled Aviptadil, 100 μg 3x daily vs. placebo 3x daily. The primary outcome will be progression to ARDS 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. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or 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.

Detailed Description:

Detailed Description:

Attack of the Alveolar Type II (ATII) cell via its ACE2 surface receptor by the SARS-CoV-2 virus leads to respiratory failure, morbidity, and frequently mortality in COVID-19. There is no approved treatment that specifically targets the pulmonary injury. Vasoactive Intestinal Peptide (VIP) is known to target the VPAC1 receptor of the ATII cell and to protect that cell against all manner of injuries, including smoke inhalation, exposure to stomach acid, and exposure to infectious agents. VIP prevents apoptosis, blocks cytokines, lowers TNFα levels, reverses CD4/CD8 ratio, and reduces cough and dyspnea in nonclinical and clinical studies. Aviptadil, a synthetic form of Vasoactive Intestinal Polypeptide (VIP) has been awarded FDA Orphan Drug Designation for the treatment of ARDS and Pulmonary Hypertension and EMEA Orphan Drug Designation for the treatment of ARDS and Sarcoid. RLF-100 (Aviptadil) has been granted FDA Fast Track Designation for the treatment of ARDS/Acute Lung Injury in COVID-19.

Acute Respiratory Distress Syndrome (ARDS) is a known lethal complication of Corona Virus (SARS-CoV-2) infection. Conventional medical therapy, including intensive care and respiratory support is associated with an 80% mortality.

The objective of this study is to identify patients with non-Acute Lung Injury (NALI) in moderate and severe COVID-19 who have not yet developed respiratory failure and to treat them with inhaled Vasoactive Intestinal Polypeptide (VIP) in the hope of preventing progression from NALI to Acute Lung Injury and ARDS Critical COVID-19 with Respiratory Failure. Aviptadil, a synthetic form of Vasoactive Intestinal Polypeptide (VIP) has been awarded FDA Orphan Drug Designation for the treatment of ARDS.

Nonclinical studies demonstrate that VIP is highly 70% concentrated in the lung, where it binds primarily to ATII cells. VIP prevents NMDA-induced caspase-3 activation in the lung, inhibits IL6 and TNFa TNFα production, protects against HCl-induced pulmonary edema, These and other effects have been observed in numerous animal model systems of lung injury in mice, rats, guinea pigs, sheep, swine, and dogs. In these models, Aviptadil restores barrier function at the endothelial/alveolar interface and thereby protects the lung and other organs from failure.

Both intravenous and inhalation preclinical toxicology and safety pharmacology have been performed in four species, with a six month trial of inhaled RLF-100 in primates.

Aviptadil is approved for human use in Europe and has a demonstrated 20 year history of safety in numerous trials for Sarcoid, Pulmonary Fibrosis, Bronchospasm, Erectile Dysfunction, and a phase I trial in ARDS. In that phase I trial, 8 patients with severe ARDS on mechanical ventilation were treated with ascending doses of VIP. Seven of the 8 patients were successfully extubated and were alive at the five day timepoint. Six left the hospital and one died of an unrelated cardiac event.

Five GCP phase 2 trials of aviptadil RLF-100 have been conducted under European regulatory authority. Numerous Non GCP healthy volunteer studies have shown that i.v. infusion of Aviptadil is well tolerated with few adverse effects including alterations in blood pressure, heart rate, or ECG. In addition to published studies of human use, Aviptadil has been used on a compounded basis in certain ICUs for many years in the belief that it preserves life and restores function in pulmonary hypertension, ARDS, and Acute Lung Injury (ALI).

In this study, patients patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer.

In this study, patients who are hospitalized for COVID-19 infection with NALI but no evidence of ARDS will be randomly allocated to Aviptadil administered by inhalation in addition to Standard of Care vs. Placebo plus Standard of Care. The primary endpoints outcome will be progression to ARDS in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days and improvement in blood oxygenation . Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

Conditions
Conditions: SARS-CoV 2
COVID
ARDS
ALI
Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
Dyspnea
Keywords: Corona Virus
VIP
Aviptadil
Vasoactive Intestinal Polypeptide
Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2/Phase 3
Interventional Study Model: Parallel Assignment
Multicenter Randomized Placebo-controlled Trial
Number of Arms: 2 4
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 144 288 [Anticipated]
Arms and Interventions
Arms Assigned Interventions
Experimental: Inhaled Aviptadil (VIP)+Standard of Care Experimental: Moderate COVID-19 RLF-100
Patients with Moderate COVID-19 to be treated with inhaled RLF-100 (aviptadil) by mesh nebulizer 100μg 3x daily
Drug: RLF-100 (aviptadil (VIP )
Inhaled RLF-100 (aviptadil) 100μg 3x daily by mesh nebulizer
Device: Nebulized administration of RLF-100 or Placebo
Use of 510(k) cleared mesh nebulizer to deliver investigational product
Experimental: Moderate COVID-19 Placebo +Standard of Care
Patients with Moderate COVID-19 to be treated with inhaled placebo 3x daily
Drug: Placebo
Normal Saline Inhalation
Device: Nebulized administration of RLF-100 or Placebo
Use of 510(k) cleared mesh nebulizer to deliver investigational product
Experimental: Severe COVID-19 RLF-100
Patients with Severe COVID-19 to be treated with inhaled RLF-100 (aviptadil) by mesh nebulizer 100μg 3x daily
Drug: RLF-100 (aviptadil)
Inhaled RLF-100 (aviptadil) 100μg 3x daily by mesh nebulizer
Device: Nebulized administration of RLF-100 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 RLF-100 or Placebo
Use of 510(k) cleared mesh nebulizer to deliver investigational product
Outcome Measures
Primary Outcome Measures:
1. Progression to ARDS
Progression to ARDS is defined as the need for mechanical ventilation

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

[Time Frame: 28 days]
3. RDP Dsypnea Scale

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



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

[Time Frame: 28 days]
Eligibility
Minimum Age: 18 12 Years
Maximum Age: 75 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. COVID-19 with evidence of Lung Injury as demonstrated by PO2 of <90 measured by pulse oximetry. Moderate or Severe COVID-19 by FDA definition with no evidence of Respiratory Failure
  2. Capable of using mesh nebulizer to administer medication with assistance if needed
  3. Physician determination that patient is on maximal SOC therapy-

Exclusion Criteria:

  1. Evidence of ARDS or need for mechanical ventilation Evidence of Respiratory Failure
  2. Use or impending use of ventilation or high flow nasal oxygen 20L or greater
  3. Impending ICU admission
  4. Pregnancy;
  5. Age <18 years;
  6. Diastolic pressure < 65 mm Hg;
  7. Irreversible underlying condition with projected fatal course;
  8. Immunosuppressive treatment for transplant or other reasons;
  9. Cancer, renal failure, congestive heart failure, neurological disorder
  10. Recent myocardial infarction
  11. Diarrhea

4) Age <12 years; 5) Diastolic pressure < 65 mm Hg; 6) Irreversible underlying condition with projected fatal course; 7) Immunosuppressive treatment for transplant or other reasons; 8) Cancer, renal failure, congestive heart failure, neurological disorder 9) Recent myocardial infarction with Troponin >0.5

Contacts/Locations
Central Contact: Robert E Besthof, MIM
Telephone: +48425461134
Email: rbesthof@neurorxpharma.com
Study Officials: Jonathan C Javitt, MD, MPH
Study Chair
NeuroRx
Locations:
IPDSharing
Plan to Share IPD: Yes
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame:
Access Criteria:
URL:
References
Citations:
Links: Description: Javitt JC: Perspective: The potential role of vasoactive intestinal peptide in treating COVID-19
Description: Pathogenesis of COVID-19 from a cell biologic perspective
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services