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

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Biological: DVX201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent Be between 18 and 80 years of age and weigh at least 40 kg, inclusive, at time of informed consent 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 Symptomatic onset within 7 days of signing consent Require hospitalization and meet the following: Radiographic infiltrates by imaging (chest x-ray, CT scans) Able to maintain a SpO2 ≥ 93% at rest. Supplemental oxygen to a maximum 4L by low flow O2-delivery is allowed, but not required 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 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: Weight less than 40 kg Be ventilator dependent or be diagnosed with ARDS or multi-system organ failure Have elevated oxygen requirement exceeding 4L oxygen by nasal cannula Expected intubation within 24 hours per investigators assessment Expected discharge from hospital within 72 hours of planned DVX201 date of infusion Have a known hypersensitivity to constituents of DVX201, such as DMSO or atinhistamine medications Have a history of symptomatic pulmonary or chronic pulmonary disease or severe asthma on chronic therapy for treatment Have a history of baseline requirement of supplemental oxygen prior to COVID-19 diagnosis Active autoimmune disorder or other medical condition requiring systemic immunosuppressive therapy (including steroids at > 5 mg prednisone or equivalent daily) Be pregnant or breast-feeding Have inadequate organ function as defined by: Acute or chronic kidney injury requiring intermittent or continuous venovenous hemodialysis or estimated GFR of < 60 mL/min/1.73 m2 Abnormal liver function defined by AST (aspartate aminotransferase), ALT (alanine aminotransferase) or alkaline phosphatase ≥ 5 times the upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an, open-label, non-randomized Phase 1 dose-finding study of DVX201 in patients hospitalized with COVID-19. Subjects will enroll and the MTD and/or the RP2D of DVX201 will be determined utilizing a modified 3+3 enrollment schema.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DVX201 infusion<br>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<br>* Single infusion of DVX201, an allogeneic NK cell therapy derived from CD34+ hematopoietic stem cells<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK cells, Cell therapy, Allogeneic