COVID-19
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALSARS-CoV-2 Specific T Cells
Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.
Sponsors
Duke-NUS Graduate Medical School
National University Hospital, Singapore
Singapore General Hospital
Sengkang General Hospital
Changi General Hospital
KK Women's and Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicities | till Day 28 after infusion of SARS-CoV-2 specific T cells | Dose-limiting toxicities are defined as \>Grade 3 Common Toxicity Criteria associated with the therapeutic cells. Toxicity rate will be summarized descriptively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to improvement by one category on a WHO ordinal scale | one month | Measured by time-to-improvement by one category on a WHO ordinal scale after infusion of SARS-CoV-2 specific T cells |
| Time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells | two months | Measured by time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells |
| National Early Warning Score (NEWS) | one month | Measured by change in daily NEWS score after infusion of SARS-CoV-2 specific T cells |
| Time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion | two months | Measured by the time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion |
| Overall survival (OS) at 3 months after infusion of SARS-CoV-2 specific T cells | three months | Measured by the proportion of recipients surviving at 3 months after infusion of SARS-CoV-2 specific T cells |
| Duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood circulation | two months | Measured by the duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood |
Countries
Singapore
Contacts
Primary ContactMichaela Seng
Outcome results
None listed