A Phase II Safety and Tolerability Study of TCB008 in Patients With COVID-19

Study Overview
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Brief Summary
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A Phase II safety and tolerability study of expanded gamma delta T cell lymphocytes (TCB008) in patients diagnosed with COVID-19.

Detailed Description
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The aim of this Phase II study is to evaluate the safety and tolerability of ex-vivo expanded gamma delta T-cells (TCB008) manufactured from a single allogeneic unmatched or partially, randomly matched, unrelated donor, in patients with COVID-19. The trial is designed to identify an optimal, safe dose of allogeneic γδ T cells in a population of patients with COVID-19. There will be 4 patient Cohorts. Cohorts 1 - 3 will receive a pre-defined dosing schedule, with Cohort 4 being treated with a dose selected upon completion of the first 3 Cohorts. In order to investigate immunogenicity assessment/sensitisation effects, patients in the expansion cohort who do not experience adverse reactions meeting dose limiting toxicity (DLT) criteria after the first administration will receive re-infusion with the same dose on Day 10 after the first infusion.

Official Title
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A Phase II Safety and Tolerability, Inter-patient Pre-defined Dose Study of Ex-vivo Expanded Allogeneic γδ T-lymphocytes (TCB008) in Patients Diagnosed With COVID-19

Conditions
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COVID - 19

Intervention / Treatment
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* Drug: TCB008


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily participating in the clinical study; fully understanding and being fully informed of the study and having signed the Informed Consent Form (ICF); - willingness and capability to complete all the study procedures Age 18-65 years (inclusive) at the time of signing ICF Any gender Patients with a positive diagnosis of COVID-19 either identified in the community as at risk of progression of disease or already hospitalized with new changes on CXR or CT scan compatible with COVID19, or patients requiring supplemental oxygen, but for whom dexamethasone is not yet indicated according to current standard of care recommendations. The product would be indicated for patients categorized as per the WHO ordinal scale 2,3 or 4: i.e., ambulatory (or community identified) patients with limitations of activity, judged as at risk for progression of disease, as well as hospitalized patients not yet requiring oxygen therapy or receiving non-invasive low flow oxygen therapy, which does not yet indicate the need to commence dexamethasone therapy. Exclusion Criteria Patients requiring high-flow oxygen therapy and/or dexamethasone according to the current standard of care. Patients suffering from severe cognitive impairment or mental illness Pregnant and/or lactating women Patients participating in other CTIMP clinical studies at the same time Active autoimmune disease or Graft versus Host Disease (GVHD) Patients with any major comorbidity (e.g., diabetes, cardiovascular and pulmonary diseases, malignancies on active treatment) unless their pre-morbid Karnofsky performance status was ≥ 80% Patients with documented history of immunological disorders Immunocompromised patients defined as those with human immunodeficiency virus infection with a CD4 cell count of less than 200 per microliter or uncontrolled viremia, prolonged use of glucocorticoids or other immunomodulating medications, a history of bone marrow or organ transplantation ALT / AST> 5 times the upper limit of the normal Neutrophils <500 / mm3 Platelets <50.000 / mm3 Patients known or suspected to have sensitivity against mouse immunoglobulins or iron-dextran.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, safety and tolerability, escalating dose, single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: γδ T cells (IMP, TCB008)<br>Patients will receive an infusion of γδ T cells (IMP, TCB008) following informed consent after admission to hospital for SARS-CoV-2 infection (COVID-19). | Drug: TCB008<br>* administration of gamma delta T cells by IV bolus injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of treatment emergent adverse events (AEs) - Safety | Safety of IMP assessed by incidence of treatment-emergent adverse events (AEs) per patient, graded by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | 30 and 90 days after IMP administration | 
| Incidence of dose-limiting toxicities (DLTs) - Tolerability | Tolerability of IMP assessed by incidence of dose-limiting toxicities (DLT's) graded by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | 30 and 90 days after IMP administration | 
| Establish Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) - Tolerability | Tolerability of IMP assessed by incidence of dose-limiting toxicities (DLT's) graded by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 | Approx 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ATMP