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

Phase 2

Withdrawn

• Conditions: COVID - 19
• Interventions: Drug: TCB008

• Registration Number: NCT04834128
• Lead Sponsor: TC Biopharm

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-03-29
• Study First Submitted QC: 2021-04-05
• Study First Posted: 2021-04-06
• Study Start: 2021-12-13
• Primary Completion: 2022-04-13
• Study Completion: 2022-04-13
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-20
• Last Update Posted: 2023-04-21

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
γδ T cells (IMP, TCB008)	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).

Primary Outcome Measures

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

Trial Locations

Locations (1)

Royal Victoria Infirmary; 🇬🇧 Newcastle, United Kingdom