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

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

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

Study Overview

• Status: Withdrawn
• Conditions: COVID - 19
• Intervention / Treatment: Drug: TCB008

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Newcastle, United Kingdom
    • Royal Victoria Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. Age 18-65 years (inclusive) at the time of signing ICF
3. Any gender

4. 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

1. Patients requiring high-flow oxygen therapy and/or dexamethasone according to the current standard of care.
2. Patients suffering from severe cognitive impairment or mental illness
3. Pregnant and/or lactating women
4. Patients participating in other CTIMP clinical studies at the same time
5. Active autoimmune disease or Graft versus Host Disease (GVHD)
6. 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%
7. Patients with documented history of immunological disorders
8. 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
9. ALT / AST> 5 times the upper limit of the normal
10. Neutrophils <500 / mm3
11. Platelets <50.000 / mm3
12. Patients known or suspected to have sensitivity against mouse immunoglobulins or iron-dextran.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: γδ T cells (IMP, TCB008); 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; administration of gamma delta T cells by IV bolus injection

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of gamma delta T cells	Assessment of the persistence of gamma delta T cells in the peripheral blood os dosed patients using flow cytometry	Approx 1 year
Phenotype of gamma delta T cells	Assessment of the phenotype of gamma delta T cells in the peripheral blood of dosed patients using flow cytometry	Approx 1 year

Collaborators and Investigators

• Sponsor: TC Biopharm

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): April 13, 2022
• Study Completion (Actual): April 13, 2022

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: ATMP
• Other Study ID Numbers: TCB008-002

Drug and device information, study documents

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