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

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ClinicalTrials.gov Identifier: NCT04366115
Recruitment Status : Not yet recruiting
First Posted : April 28, 2020
Last Update Posted : January 7, 2021
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
AVM Biotechnology LLC

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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)
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
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023


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 Name: 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 Name: 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.




Primary Outcome Measures :
  1. Dose-Limiting Toxicities [ Time Frame: 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.

  2. 28 day all-cause mortality will be a primary end point for Phase 1 and 2 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04366115


Contacts
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Contact: Madhavi Malladi, PhD 1.513-384-6717 M.Malladi@Medpace.com
Contact: Bethelhem Lebneh 2069069922 blebneh@avmbiotech.com

Sponsors and Collaborators
AVM Biotechnology LLC
Medpace, Inc.
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Responsible Party: AVM Biotechnology LLC
ClinicalTrials.gov Identifier: NCT04366115    
Other Study ID Numbers: AVM0703-101
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: January 7, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AVM Biotechnology LLC:
ARDS
COVID19
Influenza
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action