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

Phase 1

• Conditions: COVID-19
• Interventions: Biological: SARS-CoV-2 Specific T Cells

• Registration Number: NCT04457726
• Lead Sponsor: KK Women's and Children's Hospital

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.

Study Timeline

• Status Verified: 2020-06
• Study Start: 2020-07-01
• Study First Submitted: 2020-07-02
• Study First Submitted QC: 2020-07-02
• Last Update Submitted: 2020-07-02
• Study First Posted: 2020-07-07
• Last Update Posted: 2020-07-07
• Primary Completion: 2021-03
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Recipients with severe COVID-19	SARS-CoV-2 Specific T Cells	Recipients who are confirmed positive by SARS-CoV-2 testing and have severe COVID-19.
Recipients with mild to moderate COVID-19	SARS-CoV-2 Specific T Cells	Recipients who are confirmed positive by SARS-CoV-2 testing and have mild to moderate COVID-19.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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
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-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
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

Trial Locations

Locations (5)

Changi General Hospital; 🇸🇬 Singapore, Singapore

KK Women's and Children's Hospital; 🇸🇬 Singapore, Singapore

Sengkang General Hospital; 🇸🇬 Singapore, Singapore

National University Hospital; 🇸🇬 Singapore, Singapore

Singapore General Hospital; 🇸🇬 Singapore, Singapore