Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Recipients with severe COVID-19 Recipients who are confirmed positive by SARS-CoV-2 testing and have severe COVID-19. |
Biological: SARS-CoV-2 Specific T Cells
Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.
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Experimental: Recipients with mild to moderate COVID-19 Recipients who are confirmed positive by SARS-CoV-2 testing and have mild to moderate COVID-19. |
Biological: SARS-CoV-2 Specific T Cells
Eligible patients will receive a single infusion of SARS-CoV-2 specific T cells intravenously.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 1 to 90 years
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Tested positive for SARS-CoV-2 <72 hours prior to enrolment
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Predicted to have high chance of mortality:
Group 1: Severe disease, defined by one or more of the following:
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Dyspnea
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Respiratory frequency ≥ 30/min
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Blood oxygen saturation ≤ 93%
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Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300
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Lung infiltrates > 50% within 24 to 48 hours
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Respiratory failure
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Septic shock
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Multiple organ dysfunction or failure
Group 2: Mild to moderate disease, at high risk of progression to severe disease. For example,
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Age > 65 years
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Chronic health conditions such as chronic lung disease, cardiovascular disease, diabetes mellitus, obesity, end-stage renal disease or liver disease
Exclusion Criteria:
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Rapidly progressive disease with anticipated life-expectancy <72 hours
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Receiving steroid (>0.5mg/kg methylprednisolone equivalent)
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Pregnancy
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Breastfeeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Changi General Hospital | Singapore | Singapore | ||
2 | KK Women's and Children's Hospital | Singapore | Singapore | ||
3 | National University Hospital | Singapore | Singapore | ||
4 | Sengkang General Hospital | Singapore | Singapore | ||
5 | Singapore General Hospital | Singapore | Singapore |
Sponsors and Collaborators
- KK Women's and Children's Hospital
- Duke-NUS Graduate Medical School
- National University Hospital, Singapore
- Singapore General Hospital
- Sengkang General Hospital
- Changi General Hospital
Investigators
- Principal Investigator: Wing Hang Leung, KK Hospital, SingHealth Duke NUS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- COVID-T 2.0