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Evaluating AVM0703 for Treatment of COVID-19 (AVM0703)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04366115
Recruitment Status : Not yet recruiting
First Posted : April 28, 2020
Last Update Posted : May 27, 2020
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
AVM Biotechnology LLC

Brief Summary:
This is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: AVM0703 Drug: Placebo Drug: hydrocortisone Phase 1 Phase 2

Detailed Description:

Phase 1 The primary objective of the Phase 1 portion of the study is to evaluate the safety and efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.

The secondary objective of the Phase 1 portion of the study is to evaluate the pharmacokinetics (PK) of ascending doses of AVM0703.

The exploratory objective of the Phase 1 portion 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.

Phase 2 The primary objective of the Phase 2 portion of the study is to determine the potential efficacy of AVM0703 when administered at the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) in patients with severe or life-threatening COVID-19 infection.

The secondary objective of the Phase 2 portion of the study is to gain further information about the safety of AVM0703 in patients with severe or life-threatening COVID-19 infection.

The exploratory objective of the Phase 2 portion of the study is to assess potential biomarkers indicative of NKT cell activity and biomarkers predictive of responders to AVM0703 in peripheral blood and bronchoalveolar lavage.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study Evaluating AVM0703 in Patients With COVID-19
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AVM0703
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

Drug: hydrocortisone
Hydrocortisone is administered in circadian rhythm to prevent neuropsychiatric side-effects
Other Name: physiologic hydrocortisone

Placebo Comparator: Placebo
GMP excipients
Drug: Placebo
Single IV infusion in normal saline over 1 hour to patients.

Drug: hydrocortisone
Hydrocortisone is administered in circadian rhythm to prevent neuropsychiatric side-effects
Other Name: physiologic hydrocortisone




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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 severe, immediately life-threatening COVID-19, according to COVID-19 Critical Illness Salvage Criteria, as follows:

    1. Severe acute respiratory distress syndrome (Berlin Criteria [JAMA 2012]);
    2. Refractory hypoxemia on invasive mechanical ventilation despite rescue measures (prone positioning, positive end-expiratory airway pressure [PEEP] ladder, inhaled pulmonary vasodilators, recruitment maneuvers and/or neuromuscular blockade) as demonstrated by two of the following:

    i. 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; ii. Persistence of SpO2 ≤87% on room air by pulse oximetry for more than 6 hours; iii. Oxyhemoglobin desaturation to SpO2 ≤80% on room air during and/or following patient position changes in the bed;

  4. 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/assent through 1 month after study drug infusion;
  5. Must be able to provide informed consent. A legally authorized representative is allowed to provide informed consent for patients on life support who are unable to provide informed consent.

Exclusion Criteria

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

  1. Moribund subject who, in the opinion of the Investigator, is not expected to survive at least 48 hours;
  2. Known hypersensitivity or allergy to the study drug or any of its excipients;
  3. Known gastric or duodenal ulcer;
  4. Uncontrolled type 1 or type 2 diabetes;
  5. Active and untreated bacterial, fungal, parasitic, or viral infection; patients with history of a positive hepatitis B surface antigen and/or hepatitis B core antibody must have a negative hepatitis B PCR assay result; patients with history of a positive hepatitis C virus antibody (HCV Ab) test must have a negative hepatitis C PCR assay result ;
  6. Known to have received a live vaccination within the previous 3 months ;
  7. Immunocompromised patients: bone marrow or solid organ transplant; or history of human immunodeficiency virus 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;
  8. End-stage liver disease (Childs-Pugh Score >10);
  9. Dialysis-dependent due to underlying chronic renal disease; patients who require dialysis for treatment of renal failure due to complications of COVID-19 infection are not excluded from enrollment;
  10. Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, 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 ≥100 mmHg or systolic blood pressure ≥150 mmHg) despite antihypertensive therapy; patients with heart failure requiring medical support due solely to complications of COVID-19 infection are not excluded from enrollment;
  11. Significant screening electrocardiogram (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;
  12. Any malignancy requiring active treatment ;
  13. Manic-depressive disorder, schizophrenia, or a history of severe depression or substance abuse;
  14. Pregnant or breastfeeding;
  15. Concurrent enrollment in any other clinical study involving administration of a novel (i.e., unapproved) investigational pharmacological agent(s). Concurrent enrollment in observational and device studies and studies involving administration of pharmacological agent(s) approved for other indications (e.g., hydroxychloroquine, remdesivir), will be considered on a case by case basis and in consultation with the Medical Monitor;
  16. Treatment with novel, unapproved, or off-label treatments for COVID-19 (e.g., hydroxychloroquine), not administered as part of a formal clinical study, where the first dose was initiated within 72 hours of AVM0703 start;
  17. 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: May 27, 2020
Last Verified: May 2020
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
Additional relevant MeSH terms:
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Dexamethasone
Dexamethasone acetate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
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