Allogeneic Natural Killer (NK) Cell Therapy in Subjects Hospitalized for COVID-19

A Phase 1 Study of DVX201, an Allogeneic Natural Killer (NK) Cell Therapy in Subjects Hospitalized for COVID-19

This study is being done to determine the highest tolerated dose of an investigational cell therapy called DVX201 in patients hospitalized with COVID-19. DVX201 is an allogeneic NK (natural killer) cell therapy. NK cells are a normal part of your immune system that have the ability to identify and kill cells in the body that are infected by viruses such as COVID-19. There is evidence that both NK cell exhaustion and low numbers of NK cell in the blood occur in COVID-19 patients, and this may contribute to worsening of the infection. Therefore, infusion of healthy functional NK cells (like DVX201) may help overcome COVID-19 infection and prevent progression of the disease. This study is being done to look at the safety and tolerability of DVX201 in patients with COVID-19 and to gather information on how COVID-19 responds to treatment with DVX201.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Biological: DVX201

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
2. Be between 18 and 80 years of age and weigh at least 40 kg, inclusive, at time of informed consent
3. Be confirmed positive for COVID-19 (SARS-CoV-2) infection as determined by validated clinical PCR assay or by a hospital validated serological test within 7 days of consent
4. Symptomatic onset within 7 days of signing consent

5. Require hospitalization and meet the following:

   1. Radiographic infiltrates by imaging (chest x-ray, CT scans)
   2. Able to maintain a SpO2 ≥ 93% at rest. Supplemental oxygen to a maximum 4L by low flow O2-delivery is allowed, but not required
   3. Meet 2 out of the 3 following criteria:

   i. IL-6 < 150 pg/mL ii. CRP < 100 mg/L (10 mg/dL) iii. Ferritin < 1000 ng/mL

6. Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study and for a minimum of 90 days after study treatment

Exclusion Criteria:

1. Weight less than 40 kg
2. Be ventilator dependent or be diagnosed with ARDS or multi-system organ failure
3. Have elevated oxygen requirement exceeding 4L oxygen by nasal cannula
4. Expected intubation within 24 hours per investigators assessment
5. Expected discharge from hospital within 72 hours of planned DVX201 date of infusion
6. Have a known hypersensitivity to constituents of DVX201, such as DMSO or atinhistamine medications
7. Have a history of symptomatic pulmonary or chronic pulmonary disease or severe asthma on chronic therapy for treatment
8. Have a history of baseline requirement of supplemental oxygen prior to COVID-19 diagnosis
9. Active autoimmune disorder or other medical condition requiring systemic immunosuppressive therapy (including steroids at > 5 mg prednisone or equivalent daily)
10. Be pregnant or breast-feeding

11. Have inadequate organ function as defined by:

    1. Acute or chronic kidney injury requiring intermittent or continuous venovenous hemodialysis or estimated GFR of < 60 mL/min/1.73 m2
    2. Abnormal liver function defined by AST (aspartate aminotransferase), ALT (alanine aminotransferase) or alkaline phosphatase ≥ 5 times the upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DVX201 infusion; Subjects will enroll and the MTD and/or the recommended phase 2 dose of DVX201 will be determined utilizing a modified "3+3" enrollment schema. This study will enroll a minimum 3 subjects who each receive a single dose of DVX201 and who are evaluable for toxicities at each dose level. Depending on the occurrence of DLTs and the number of dose levels evaluated, additional subjects may be enrolled (approximately 3-15 additional subjects). All subjects will be followed for 28 days post infusion of DVX201.

Biological: DVX201; Single infusion of DVX201, an allogeneic NK cell therapy derived from CD34+ hematopoietic stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities (DLT)	DLTs defined as grade 3 or greater infusion related reactions within 24 hours and any treatment emergent toxicity grade 3 or greater within 7 days apart from known complications of COVID-19	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction/clearance of viral load/viral shedding	time in days to clearance of virus	through study completion, an average of 28 days post cell infusion
Oxygen requirements	Time in days on supplemental oxygen and time in days to resolution of hypoxia	through study completion, an average of 28 days post cell infusion
Disease progression	Incidence of disease progression to ICU admission and/or ventilatory support	through study completion, an average of 28 days post cell infusion
CRS	Incidence of cytokine release syndrome requiring clinical intervention	through study completion, an average of 28 days post cell infusion
hospital discharge	Time in days post infusion of DVX201 to hospital discharge	through study completion, an average of 28 days post cell infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of time that DVX201 (NK cells) remain in the blood	Evaluation of persistence of DVX201 in the peripheral blood	through 28 days post infusion

Collaborators and Investigators

• Sponsor: Coeptis Therapeutics
• Collaborators: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Josh Hill, MD, Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): June 7, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Allogeneic; Cell therapy; NK cells
• 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; COVID-19
• Other Study ID Numbers: DVX201-COV-01; RG1121470 (Other Identifier: Fred Hutchinson Cancer Research Center)

Drug and device information, study documents

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