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

Sponsor
KK Women's and Children's Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04457726
Collaborator
Duke-NUS Graduate Medical School (Other), National University Hospital, Singapore (Other), Singapore General Hospital (Other), Sengkang General Hospital (Other), Changi General Hospital (Other)
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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
  • Biological: SARS-CoV-2 Specific T Cells
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

Study Type:
Interventional
Anticipated Enrollment :
18 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19
Anticipated Study Start Date :
Jul 1, 2020
Anticipated Primary Completion Date :
Mar 1, 2021
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
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.

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

  1. 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

  1. National Early Warning Score (NEWS) [one month]

    Measured by change in daily NEWS score after infusion of SARS-CoV-2 specific T cells

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

Ages Eligible for Study:
1 Year to 90 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
KK Women's and Children's Hospital
ClinicalTrials.gov Identifier:
NCT04457726
Other Study ID Numbers:
  • COVID-T 2.0
First Posted:
Jul 7, 2020
Last Update Posted:
Jul 7, 2020
Last Verified:
Jun 1, 2020
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 7, 2020