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.

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