Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19

Study Overview
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Brief Summary
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The overall objective of this project is to develop an emergent treatment protocol using adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be manufactured expeditiously and these cells are safe and effective for the treatment of severe SARS-CoV-2 infections.

Detailed Description
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A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19). Currently, no vaccine has been proven to be effective. While waiting for vaccine to be developed, passive immunity can be acquired immediately by adoptive transfer of SARS-CoV-2 specific T cells from convalescent donors into newly infected patients. The overall objective of this project is to develop an emergent treatment protocol using adoptive T-cell therapy for the treatment of severe COVID-19. The central hypothesis is that SARS-CoV-2 specific T cells from convalescent donors who have recovered from COVID-19 can be manufactured expeditiously and these cells are safe and effective for the treatment of severe SARS-CoV-2 infections. Part Two of this project is to assess the safety and efficacy of these T cells in patients with COVID-19.

Official Title
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Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: SARS-CoV-2 Specific T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1 to 90 years Tested positive for SARS-CoV-2 <72 hours prior to enrolment Predicted to have high chance of mortality: Group 1: Severe disease, defined by one or more of the following: Dyspnea Respiratory frequency ≥ 30/min Blood oxygen saturation ≤ 93% Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300 Lung infiltrates > 50% within 24 to 48 hours Respiratory failure Septic shock Multiple organ dysfunction or failure Group 2: Mild to moderate disease, at high risk of progression to severe disease. For example, Age > 65 years Chronic health conditions such as chronic lung disease, cardiovascular disease, diabetes mellitus, obesity, end-stage renal disease or liver disease Exclusion Criteria: Rapidly progressive disease with anticipated life-expectancy <72 hours Receiving steroid (>0.5mg/kg methylprednisolone equivalent) Pregnancy Breastfeeding

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 90 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recipients with severe COVID-19<br>Recipients who are confirmed positive by SARS-CoV-2 testing and have severe COVID-19. | Biological: SARS-CoV-2 Specific T Cells<br>* Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.<br>|
| Experimental: Recipients with mild to moderate COVID-19<br>Recipients who are confirmed positive by SARS-CoV-2 testing and have mild to moderate COVID-19. | Biological: SARS-CoV-2 Specific T Cells<br>* Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicities | Dose-limiting toxicities are defined as >Grade 3 Common Toxicity Criteria associated with the therapeutic cells. Toxicity rate will be summarized descriptively. | till Day 28 after infusion of SARS-CoV-2 specific T cells | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Early Warning Score (NEWS) | Measured by change in daily NEWS score after infusion of SARS-CoV-2 specific T cells | one month | 
| Time to improvement by one category on a WHO ordinal scale | Measured by time-to-improvement by one category on a WHO ordinal scale after infusion of SARS-CoV-2 specific T cells | one month | 
| Time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells | Measured by time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells | two months | 
| Duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood circulation | Measured by the duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood | two months | 
| Time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion | Measured by the time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion | two months | 
| Overall survival (OS) at 3 months after infusion of SARS-CoV-2 specific T cells | Measured by the proportion of recipients surviving at 3 months after infusion of SARS-CoV-2 specific T cells | three months |