Evaluating AVM0703 for Treatment of COVID-19 or Influenza-mediated ARDS (AVM0703)

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study Evaluating AVM0703 in Patients With Acute Respiratory Distress Syndrome

This is a randomized, double-blinded, placebo-controlled study of AVM0703 administered as a single intravenous (IV) infusion to patients with moderate or severe immediately life-threatening Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 or influenza (A or B). The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose of AVM0703 in these ARDS patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Covid19; Influenza, Human; ARDS
• Intervention / Treatment: Drug: AVM0703; Drug: Placebo

Detailed Description

The primary objective of the study is to evaluate the safety and tolerability of a single dose of AVM0703 in patients with moderate, severe or immediately life-threatening ARDS due to COVID-19 or Influenza (A or B) infection.

The secondary objectives of the study are to 1) evaluate the pharmacokinetics (PK) and 2) evaluate potential clinical findings following a single dose of AVM0703.

The exploratory objective of the study is to assess potential biomarkers indicative of natural killer T (NKT) cell activity and biomarkers predictive of response to AVM0703 in peripheral blood and bronchoalveolar lavage.

The results of the Phase 1 study will guide the design of the Phase 2 study.

• Study Type: Interventional
• Enrollment (Anticipated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Janet R Rea, MSPH; Phone Number: 2069069922; Email: jrea@avmbiotech.com
• Study Contact Backup: Name: Mia Lor; Phone Number: 2069069922; Email: mlor@avmbiotech.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients who meet all of the following criteria will be eligible to participate in the study:

1. Age ≥18 years;
2. Must have laboratory confirmed COVID-19;

3. Must have moderate or severe, immediately life-threatening COVID-19 or Influenza (A or B), as follows:

   a. COVID-19 patients with ARDS (Berlin Criteria) as demonstrated by:

   i. Chest radiograph or CT scan showing bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules;

   ii. Respiratory failure not fully explained by cardiac failure or fluid overload; and

   iii. Impaired oxygenation defined as Moderate (partial pressure of oxygen [PaO2]:fraction of inspired oxygen [FiO2] ratio 100 mm Hg to <200 mm Hg with positive end-expiratory airway pressure [PEEP] >5 cm H2O) or Severe (PaO2:FiO2 ratio <100 mm Hg with PEEP>5 cm H2O) on more than 2 arterial blood gases at least 6 hours apart within a 24 hour period;

   b. Influenza (A or B) patients with ARDS (Berlin Criteria) as demonstrated by:

   i. Chest radiograph or CT scan showing bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules;

   ii. Respiratory failure not fully explained by cardiac failure or fluid overload; and

   iii. Impaired oxygenation defined as Severe (PaO2:FiO2 ratio<100 mm Hg with PEEP >5 cm H2O) on more than 2 arterial blood gases at least 6 hours apart within a 24 hour period;

4. Requires invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) despite standard of care rescue measures (eg, prone positioning, and/or PEEP ladder, and/or inhaled pulmonary vasodilators, and/or recruitment maneuvers and/or neuromuscular blockade);
5. Females of childbearing potential must have a negative serum pregnancy test at screening;
6. Females of childbearing potential and nonsterile males must agree to use medically effective methods of contraception from the time of informed consent through 1 month after study drug infusion; and
7. Capable of providing informed consent, or if not capable, a legally authorized representative is capable of providing informed consent

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from participation in the study:

1. Moribund patient who, in the opinion of the Investigator, is not expected to survive at least 24 hours;
2. Known hypersensitivity or allergy to the study drug or any of its excipients;
3. D-dimer level >3 times above normal range;
4. Known gastric or duodenal ulcer;
5. Uncontrolled type 1 or type 2 diabetes, per judgment of the Investigator;
6. Active and untreated bacterial, fungal, parasitic, or viral infection other than COVID-19 or Influenza (A or B). Patients with a history of a positive hepatitis B surface antigen and/or hepatitis B core antibody must have a negative hepatitis B polymerase chain reaction (PCR) assay result. Patients with history of a positive hepatitis C virus antibody test must have a negative hepatitis C PCR assay result;
7. Positive testing for tuberculosis during screening;
8. Known to have received a live vaccine within the previous 1 month;
9. Immunocompromised patients, defined as those who have received a bone marrow or solid organ transplant on immunosuppressive therapy; or history of human immunodeficiency virus (HIV) infection who have not been taking anti retroviral therapy for at least 6 months before enrollment and/or with most recent CD4 count <200 cells/mL and/or most recent detectable viral load within the previous 6 months;
10. Moderate to End-stage liver disease (Childs-Pugh Score >10);
11. Dialysis-dependent due to underlying chronic renal disease. Note: patients who require dialysis for treatment of renal failure due to complications of COVID-19 or Influenza (A or B) infection are not excluded from enrollment;

12. Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, including: angina requiring therapy, symptomatic peripheral vascular disease, New York Heart Association Class III or IV congestive heart failure, left ventricular ejection fraction <30%, left ventricular fractional shortening <20%, or uncontrolled Grade 3 hypertension (diastolic blood pressure [DBP] >100 mm Hg or systolic blood pressure [SBP] >150 mm Hg) despite antihypertensive therapy.

    Note: patients with heart failure requiring medical support due solely to complications of COVID-19 infection are not excluded from enrollment;

13. Significant screening 12-lead ECG abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, left bundle-branch block, second degree atrioventricular (AV) block type 2, third-degree AV block, Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula average of triplicate ECGs >450 ms;
14. Manic-depressive disorder, schizophrenia, or a history of severe depression or substance abuse;
15. Pregnant or breastfeeding;
16. Concurrent enrollment in any other clinical study involving administration of a novel (ie, unapproved or not considered standard of care) investigational pharmacological agent(s). Concurrent enrollment in observational and device studies and studies involving administration of pharmacological agent(s) approved for other indications or considered emerging standard of care for treatment of COVID-19 (eg, hydroxychloroquine, remdesivir, low-dose dexamethasone), will be allowed if approved by the Sponsor;
17. Treatment with standard of care or off-label treatments for COVID-19 (eg, remdesivir), not administered as part of a formal clinical study, where the first dose was initiated within 72 hours of study drug start; and
18. Inability to obtain informed consent from the patient or legally authorized representative.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: AVM0703 COVID-19 ARDS - active; Supra-pharmacologic dexamethasone sodium phosphate	Drug: AVM0703; Single IV infusion at 10 mg/mL in normal saline over 1 hour to patients.; Other Names: Suprapharmacologic dexamethasone sodium phosphate
PLACEBO_COMPARATOR: Placebo COVID-19 ARDS - placebo; Matching placebo	Drug: Placebo; Single IV infusion in normal saline over 1 hour to patients.
ACTIVE_COMPARATOR: AVM0703 Influenza ARDS - active; Supra-pharmacologic dexamethasone sodium phosphate	Drug: AVM0703; Single IV infusion at 10 mg/mL in normal saline over 1 hour to patients.; Other Names: Suprapharmacologic dexamethasone sodium phosphate
PLACEBO_COMPARATOR: AVM0703 Influenza ARDS - placebo; Matching placebo	Drug: Placebo; Single IV infusion in normal saline over 1 hour to patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-Limiting Toxicities	The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.	0-12 months
28 day all-cause mortality will be a primary end point for Phase 1 and 2	The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.	0-12 months

Collaborators and Investigators

• Sponsor: AVM Biotechnology Inc
• Collaborators: Medpace, Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2022
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): March 1, 2025

Study Registration Dates

• First Submitted: April 26, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (ACTUAL): April 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 3, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Influenza; ARDS; COVID19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Orthomyxoviridae Infections; COVID-19; Influenza, Human; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: AVM0703-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No