Treatment of SARS-CoV-2 Virus Disease (COVID-19) in Humans With Hemopurifier® Device

• ClinicalTrials.gov Identifier: NCT04595903
• Recruitment Status: Terminated
• First Posted: October 22, 2020
• Last Update Posted: December 20, 2022
• Sponsor: Aethlon Medical Inc.
• Information provided by (Responsible Party): Aethlon Medical Inc.

Study Description

Brief Summary:

This is an Early Feasibility Study (EFS) investigating the use of the Hemopurifier® in the treatment of SARS-CoV-2 Virus Disease (COVID-19).

Condition or disease	Intervention/treatment	Phase
COVID-19	Device: Hemopurifier	Not Applicable

Detailed Description:

Up to 40 ICU patients with severe or critical illness due to confirmed COVID-19 infection will be enrolled in up to 20 investigational sites. Patients will receive a four to six-hour treatment with the Hemopurifier® extracorporeal therapy daily for up to four days until discontinued because of clinical improvement or deterioration or upon the decision of the Principal Investigator. The patients will be monitored closely with vital signs and for hemodynamic stability. Patients will be followed for adverse events and device deficiencies. Blood work will be obtained.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This trial will evaluate the use of the Hemopurifier in patients with SARS-CoV-2 Virus Disease (COVID-19). The Hemopurifier is an extracorporeal device device that combines plasma filtration, size exclusion and affinity binding of mannosylated structures including enveloped viruses and exosomes. The study will evaluate whether the device is safe in COVID-19 patients along with clearing virus and improving outcomes in infected patients. Subjects will receive a four to six hour treatment with the Hemopurifier® extracorporeal therapy daily for up to four days until discontinued because of clinical improvement or deterioration or upon decision of the Principal Investigator.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of SARS-CoV-2 Virus Disease (COVID-19) in Humans With Hemopurifier® Device
• Actual Study Start Date: June 1, 2022
• Actual Primary Completion Date: November 14, 2022
• Actual Study Completion Date: November 14, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Hemopurifier®; The Hemopurifier® will be placed within the extracorporeal circuit, all connections secured, treatment will utilize a blood pump at a flow rate of up to 200mL/min. The patients will be monitored for adverse events, device deficiencies and the development of hemodynamic instability. The treatment session will be for 4-6 hours once daily for 4 consecutive days.	Device: Hemopurifier; Hemopurifier treatments will be one four to six hour treatment session daily for up to 4 days

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse events [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Safety and tolerability
2. Incidence of device related adverse events [ Time Frame: Day 1 (Date of Consent) to Day 14 ]
   Safety and tolerability with adverse event graded at 2 or higher
3. Incidence of serious adverse events [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Safety and tolerability

Secondary Outcome Measures :

1. Length if Stay in ICU [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Length of ICU stay in days
2. In-hospital mortality [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Number of deaths during hospitalization
3. Days free of ventilatory dependency [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Number of days without ventilatory support
4. Vasopressor-free days [ Time Frame: Day 1 (Date of Consent) to Day 28 ]
   Number of days without vasopressor support
5. Sequential Organ Failure Assessment (SOFA) [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more) ]
   SOFA scoring system predicts the clinical outcome of critically ill patients.
6. Acute Physiology and Chronic Health Evaluation (APACHE) [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. 4 days or more) ]
   Measures the severity of disease for adult patients admitted to an ICU
7. SARS CoV-2 RNA levels in plasma and nasopharyngeal samples [ Time Frame: Before each filter treatment, every 2 hours during filter treatment and immediately after filter discontinued ]
   Measures viral exposure and levels of circulating virus
8. Total lymphocyte count [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more) ]
   Measurement of lymphocytes as there seems to be a correlation with the disease severity and lymphopenia.
9. C-reactive protein (CRP), IL-1, IL-6, and TNF alpha Tests [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more) ]
   Measurement of inflammatory marker levels play a role in systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complication.
10. D-dimer [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more) ]
    Measurement of D-dimer levels as levels are elevated in patients with COVID-19 and correlate with disease severity, are a reliable prognostic marker for in-hospital mortality.
11. Troponin-T [ Time Frame: Before first daily filter treatment and after the last daily filter treatment (i.e. at 4 days or more) ]
    Measurement of Troponin-T as high levels of troponin is found in COVID-19 patients.
12. Evaluation of SARS-CoV-2 RNA levels post-treatment Hemopurifier cartridges [ Time Frame: Until study completion, 1 week or for the duration of ICU admission ]
    Measures the levels of SARS-CoV-2 RNA captured in the filter
13. Evaluation of viral particle load post-treatment Hemopurifier cartridges [ Time Frame: Until study completion, 1 week or for the duration of ICU admission ]
    Measures the levels of viral particles captured in the filter

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Laboratory diagnosis of COVID-19 infection with any of the following disease characteristics:

   i. Early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS) ii. Severe disease, defined as:

   • dyspnea,
   • respiratory frequency ≥ 30/min,
   • blood oxygen saturation ≤ 93%,,
   • partial pressure of arterial oxygen to fraction of inspired oxygen ratio of <300 and/or

   • lung infiltrates >50% within 24 to 48 hours; iii. Life-threatening disease, defined as:

     1. respiratory failure,
     2. septic shock, and/or
     3. multiple organ dysfunction or failure.
2. Admission to the ICU or area of the hospital repurposed to function as an ICU for surge capacity management
3. Subject has maintained a MAP of > or = 65 without an increased dose of vasopressors for at least 2 hours and has clinical evidence of adequate volume status per investigative site criteria
4. Informed consent from the patient or legally authorized representative
5. Age > 18

Exclusion Criteria:

1. Stroke (known or suspected) within the last 3 months.
2. Severe congestive heart failure (NYHA III and IV classes).
3. Biopsy proven cancer not in remission.
4. Acute (an international normalized ratio (INR) of greater than 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of less than 26weeks' duration or chronic (Child Pugh C) liver disease.
5. Known pre-existing non-COVID-19 related hypercoagulability or other coagulopathy
6. Terminal illness with a life expectancy of < 28 days or for whom a decision of withdrawal of care is in place or imminently anticipated or patients who have received prior extracorporeal therapy and had persistent, unstable hypotension.
7. Patients with known hypersensitivity to any component of the Hemopurifier.
8. Advance directive indicating to withhold life-sustaining treatment (except Cardiopulmonary Resuscitation).

9. Contraindications to extracorporeal blood purification therapy such as:

   i. Clinically relevant bleeding disorder, ii. Contraindication to anti-coagulation, iii. Pregnancy, iv. Inability to establish functional vascular access, v. Participation in another competing investigational drug, device or vaccine trial vi. Administration of an angiotensin converting enzyme (ACE) inhibitor in the previous 14 days. vii. Platelet count < 50,000 cells/microliter

Contacts and Locations

Locations

United States, California

Hoag Hospital - Irvine

Irvine, California, United States, 92618

Loma Linda University Medical Center

Loma Linda, California, United States, 92354

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

UC Davis Health System

Sacramento, California, United States, 95817

United States, Florida

University of Miami Hospital

Miami, Florida, United States, 33136

United States, Louisiana

LSU Health Sciences Center

Shreveport, Louisiana, United States, 71103

United States, New Jersey

Cooper University Hospital

Camden, New Jersey, United States, 08103

United States, Pennsylvania

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

Valley Baptist Medical Center

Harlingen, Texas, United States, 78550

Sponsors and Collaborators

Aethlon Medical Inc.

Investigators

• Study Director: Steven LaRosa, MD; Aethlon Medical Inc.

More Information

Additional Information:

Website 

Website 

Publications:

Amundson DE, Shah US, de Necochea-Campion R, Jacobs M, LaRosa SP, Fisher CJ Jr. Removal of COVID-19 Spike Protein, Whole Virus, Exosomes, and Exosomal MicroRNAs by the Hemopurifier(R) Lectin-Affinity Cartridge in Critically Ill Patients With COVID-19 Infection. Front Med (Lausanne). 2021 Oct 8;8:744141. doi: 10.3389/fmed.2021.744141. eCollection 2021.

Gooldy M, Roux CM, LaRosa SP, Spaulding N, Fisher CJ Jr. Removal of clinically relevant SARS-CoV-2 variants by an affinity resin containing Galanthus nivalis agglutinin. PLoS One. 2022 Jul 28;17(7):e0272377. doi: 10.1371/journal.pone.0272377. eCollection 2022.

• Responsible Party: Aethlon Medical Inc.
• ClinicalTrials.gov Identifier: NCT04595903
• Other Study ID Numbers: AEMD-2020-02
• First Posted: October 22, 2020
• Last Update Posted: December 20, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Aethlon Medical Inc.:

Hemopurifier; SARS-CoV-2; COVID-19; exosomes; plasmapheresis

Additional relevant MeSH terms:

COVID-19; Virus Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases