Clinical trial NCT04457726: Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19
Official title: Part Two of Novel Adoptive Cellular Therapy With SARS-CoV-2 Specific T Cells in Patients With Severe COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: KK Women's and Children's Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Duke-NUS Graduate Medical School
name: National University Hospital, Singapore
name: Singapore General Hospital
name: Sengkang General Hospital
name: Changi General Hospital
First posted: 2020-07-07
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-Limiting Toxicities
timeFrame: till Day 28 after infusion of SARS-CoV-2 specific T cells
Secondary outcomes:
measure: National Early Warning Score (NEWS)
timeFrame: one month
measure: Time to improvement by one category on a WHO ordinal scale
timeFrame: one month
measure: Time-to-SARS-CoV-2 negativity after infusion of SARS-CoV-2 specific T cells
timeFrame: two months
measure: Duration of persistence of SARS-CoV-2 specific T cells in the recipient's blood circulation
timeFrame: two months
measure: Time-to-normalization of cytokine level, lymphocyte subsets, and gene transcriptome after T cell infusion
timeFrame: two months
measure: Overall survival (OS) at 3 months after infusion of SARS-CoV-2 specific T cells
timeFrame: three months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Sengkang General Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: KK Hospital, SingHealth Duke NUS
name: Wing Hang Leung
role: PRINCIPAL_INVESTIGATOR
References: