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

Sponsor

AVM Biotechnology LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT04366115

Collaborator

Medpace, Inc. (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
ARDS Covid19 Influenza, Human	Drug: AVM0703 Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a two-armed randomized, double-blinded, placebo control controlled study. Each arm (one arm of COVID-19 mediated ARDS and one arm of influenza (A or B) mediated ARDS will be randomized to 3:1 (active to placebo)This is a two-armed randomized, double-blinded, placebo control controlled study. Each arm (one arm of COVID-19 mediated ARDS and one arm of influenza (A or B) mediated ARDS will be randomized to 3:1 (active to placebo)

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

The pharmacist will prepare the infusion solution and medication for delivery to the patient's bedside for administration. The active and placebo medications look identical, preventing care-givers and the participant from breaking the blind.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Dose-Limiting Toxicities [0-12 months]
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.
28 day all-cause mortality will be a primary end point for Phase 1 and 2 [0-12 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

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

Age ≥18 years;
Must have laboratory confirmed COVID-19;
Must have moderate or severe, immediately life-threatening COVID-19 or Influenza (A or

B), as follows:

COVID-19 patients with ARDS (Berlin Criteria) as demonstrated by:
Chest radiograph or CT scan showing bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules;

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

Influenza (A or B) patients with ARDS (Berlin Criteria) as demonstrated by:
Chest radiograph or CT scan showing bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules;

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

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);
Females of childbearing potential must have a negative serum pregnancy test at screening;
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
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:

Moribund patient who, in the opinion of the Investigator, is not expected to survive at least 24 hours;
Known hypersensitivity or allergy to the study drug or any of its excipients;
D-dimer level >3 times above normal range;
Known gastric or duodenal ulcer;
Uncontrolled type 1 or type 2 diabetes, per judgment of the Investigator;
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;
Positive testing for tuberculosis during screening;
Known to have received a live vaccine within the previous 1 month;
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;
Moderate to End-stage liver disease (Childs-Pugh Score >10);
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;
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;

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;
Manic-depressive disorder, schizophrenia, or a history of severe depression or substance abuse;
Pregnant or breastfeeding;
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;
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
Inability to obtain informed consent from the patient or legally authorized representative.