Multicentre Open-Label Single Ascending Dose Dose-Ranging Phase I/IIa Study to Evaluate Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor TRegulatory Cell Therapy in Living Donor Renal Transplant Recipients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 7
- 主要终点
- Safety and Tolerability
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of TX200-TR101 and its effects on the donated kidney in living donor kidney transplant recipients. TX200-TR101 is a product made from a kidney transplant recipient's own immune cells, which are genetically modified and designed to help the transplant recipient's body accept their donated kidney and prevent their immune system from rejecting it.
详细描述
This is a multicentre, first-in-human, open-label, single ascending dose, dose-ranging study of autologous, chimeric antigen receptor T regulatory cells (CAR-Treg) in HLA-A2 mismatched living donor kidney transplant recipients, with a control cohort of mismatched kidney transplant recipients of similar immunological risk.The aim is for the CAR-Tregs to recognise the HLA-A2 molecule present on the donated kidney and subsequently induce and maintain immunological tolerance to the organ.
The study requires two arms - transplant recipients who will receive the study treatment TX200-TR101and control participants, who are transplant recipients who will not receive the study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Male or female aged 18 - 70 years.
- •Diagnosis of End Stage Renal Disease and waiting for a new kidney from an identified live donor.
- •Subjects who will be single organ recipients (kidney).
- •Able and willing to use contraception.
排除标准
- •HLA identical to the donor.
- •Subjects with prior organ transplant.
- •Known hypersensitivity to study medication ingredients, protocol defined immunosuppressive medications, or a significant allergic reaction to any drug.
- •Positive serology for human immunodeficiency virus (HIV) or syphilis, active or occult hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or other clinically active local or systemic infection.
- •Subjects who are Epstein-Barr Virus (EBV) seronegative.
- •Positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
- •Subjects with panel-reactive antibody (PRA) >20% within 6 months prior to enrolment.
- •Subjects with current or recent donor-specific antibodies.
- •Use of any experimental medicinal product within 3 months.
- •Current use of systemic immunosuppressive agents
- •Significant unstable or poorly controlled acute or chronic diseases (except ESRD), limited life expectancy, clinically relevant central nervous system pathology, history of drug/alcohol abuse or psychiatric disorder or other condition that is not compatible with adequate study follow-up, history of malignancy in the past 5 years and any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study.
- •Subjects with abnormal laboratory values in the following parameters:
- •Haemoglobin
- •Platelets
- •White blood cells
- •Aspartate transaminase (AST) and or alanine transaminase (ALT)
- •Total bilirubin
研究组 & 干预措施
Treatment group
Subjects undergo kidney transplant as per planned standard of care and are administered study drug post transplantation.
干预措施: TX200-TR101 (Biological)
结局指标
主要结局
Safety and Tolerability
时间窗: 28 days post infusion
Safety and tolerability of TX200-TR101 infusion evaluated by incidence and grade of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) according to CTCAE V5.0.
次要结局
- Acute graft related outcomes(Day of infusion through to Week 84)
- Long-term safety(Day of infusion through to Week 84)
- Immunosuppression(Day of infusion through to Week 84)
- Graft localization(Day of infusion through to Week 84)
- Chronic graft related outcomes(Day of infusion through to Week 84)