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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-CoV-2 Specific T Cells

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 Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Hospital
    • Contact: Lip Kun Tan
  • Singapore, Singapore
    • Recruiting
    • Singapore General Hospital
    • Contact: Yeh Ching Linn
  • Singapore, Singapore
    • Recruiting
    • Changi General Hospital
    • Contact: Roshni Sadashiv Gokhale
  • Singapore, Singapore
    • Recruiting
    • KK Women's and Children's Hospital
    • Contact: Michaela Seng
  • Singapore, Singapore
    • Recruiting
    • Sengkang General Hospital
    • Contact: Jiashen Loh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital
• Collaborators: National University Hospital, Singapore; Singapore General Hospital; Changi General Hospital; Sengkang General Hospital; Duke-NUS Graduate Medical School
• Investigators: Principal Investigator: Wing Hang Leung, KK Hospital, SingHealth Duke NUS

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: July 2, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVID-T 2.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No