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
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- TC Biopharm
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) - Tolerability
研究概览
简要总结
A Phase II safety and tolerability study of expanded gamma delta T cell lymphocytes (TCB008) in patients diagnosed with COVID-19.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- 未提供
研究组 & 干预措施
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).
干预措施: TCB008 (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) - Tolerability
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
未报告次要终点