A single ascending dose trial investigating the safety and feasibility of autologous thymus derived regulatory T cell (Tregs) treatment for the prevention of cardiac allograft vasculopathy in children receiving heart transplant
Cardiac allograft vasculopathy (CAV)
Autologous thymus-derived Tregs (TR006) infused at one of two doses (in a 3+3 design): 1. Low dose: 1 - 3 x 106 Tregs/Kg or 2. High (and highest) dose: 5 - 10 x 106 Tregs/Kg
1. Male or female children aged between 0.5 and 16 (inclusive) years of age at the date of consent/assent and date of transplant 2. Written informed consent obtained from a parent/legal guardian 3. Registered on the heart transplant list at the date of consent and received a heart transplant on enrolment 4. Receiving a single transplanted organ 5. Willing and able to comply with the study visit schedule
1. Active viral infection (with HIV, hepatitis B, hepatitis C and syphilis) at date of admission for transplant 2. Age under 0.5 year or over 16 years at date of consent and at date of transplant 3. Multi-organ transplant 4. Highly sensitive patients at high risk of rejection assessed by HLA antibody measurement 5. Allergy to any component / excipients used for the manufacture of TR006 6. Previous recipient of any organ transplant 7. History of previous sternotomy surgical procedure for congenital heart defect during which has had previous partial or full thymectomy 8. Confirmed diagnosis of DiGeorge Syndrome with absent thymus 9. Participation in another interventional Clinical Trial of Investigational Medicinal Product during the study or within 28 days prior to date of transplant (at the Chief Investigator’s discretion) 10. Pregnant and lactating patients (females of childbearing potential* with a positive urine pregnancy test at date of transplant) 11. Female patients of childbearing potential* who are not willing to use a highly effective method of contraception** for the duration of the trial (defined as from date of transplant to 12 months post Treg infusion) to prevent pregnancy, or abstain from heterosexual activity *Females of child-bearing potential are females who have experienced menarche and are not surgically sterilised (e.g., hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or post-menopausal. Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required. ** Highly effective methods of contraception are those with a failure rate of < 1% per year when employed consistently and correctly. F