Prevention of immune mediated allograft rejection in patients with end-stage renal disease (ESRD) who are tissue typed as HLA-A*02 negative and have received a kidney transplant from an HLA-A*02 positive living donor. MedDRA version: 21.1 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865
Conditions
Interventions
Product Name: Autologous HLA-A2 Chimeric Antigen Receptor T regulatory cells
Product Code: TX200-TR101
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Not yet assigned
Current Sponso
Sponsors
Sangamo Therapeutics France SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The following inclusion criteria must be met for all transplant recipients (i.e., recipients to be administered TX200-TR101 and control recipients): Inclusion Criteria (All Transplant Recipients) 1. Willing and able to provide written informed consent (IC) in accordance with local regulations and governing Independent Ethics Committee (IEC)/Institutional Review Board (IRB) requirements prior to any procedure or evaluation performed specifically for the sole purpose of the study. 2. Male or female aged between 18 and 70 (inclusive) years. 3. Have diagnosis of ESRD and currently waiting for a new kidney from an identified live donor. 4. Subjects who will be single organ recipients (kidney). 5. Women who are of childbearing potential must have a negative serum pregnancy test at screening and before transplantation. 6. Able and willing to use a highly effective method of contraception from the signing of the informed consent through the last study visit, for male and female subjects with reproductive potential. Additional Inclusion Criteria (Transplant Recipients to be Administered TX200-TR101 Only) The following additional criteria must be met for transplant recipients to be administered TX200- TR101: 1. HLA-A*02 negative typing (the kidney graft needs to be HLA A*02 positive). 2. HLA-A*69 negative typing. 3. Adequate venous access for leukapheresis, and no other contraindications for leukapheresis. Additional Inclusion Criteria (Transplant Donors for Transplant Recipients to be Administered TX200- TR101 Only) The following additional inclusion criterion must be met for transplant donors for transplant recipients to be administered TX200-TR101: 1. HLA-A*02 positive typing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 27 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: Exclusion Criteria (All Transplant Recipients) 1.HLA identical to the prospective organ donor. 2.Subjects with prior organ transplant. 3.Positive flow cytometric crossmatch using donor lymphocytes and recipient serum. 4.Subjects with panel-reactive antibody (PRA) >20% within 6 months prior to enrolment. 5. Subjects with current or recent (within 6 months) donor-specific antibodies. 6. Subjects with underlying renal disease with a high risk of disease reoccurrence in the transplanted kidney including primary focal segmental glomerulosclerosis, types I or II membranoproliferative glomerulonephritis, C3 glomerulopathy, or haemolytic-uraemic syndrome (HUS), including atypical HUS. 7. Concomitant clinically active local or systemic infection. 8. Clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, haematologic, gastrointestinal, hepatic, neurological, malignancy or infectious diseases) or laboratory abnormality (except ESRD) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the short-term safety and tolerability of TX200-TR101 from the day of TX200-TR101 infusion within 28 days post TX200-TR101 infusion.;Secondary Objective: • To evaluate the effect of TX200-TR101 on acute graft-related outcomes from the day of TX200-TR101 infusion through to Week 84 in terms of biopsy-confirmed acute rejection (BCAR). • To evaluate the effect of TX200-TR101 on long-term safety outcomes from the day of TX200-TR101 infusion through to Week 84 in terms of treatment emergent adverse events(TEAEs). • To evaluate the reduction of immunosuppression over time through to Week 84. • To evaluate TX200-TR101 localisation in the graft at Week 16. • To evaluate the effect of TX200-TR101 on chronic graft-related outcomes from the day of TX200-TR101 infusion through to Week 84. ;Primary end point(s): Incidence and grade of TEAEs, including serious adverse events (SAEs) throughout 28 days post TX200-TR101 infusion.;Timepoint(s) of evaluation of this end point: The timepoint of evaluation of the primary endpoint is given in the section above ( E.5.1) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): From the day of TX200-TR101 infusion through to Week 84 unless otherwise specified below: •Incidence of BCAR according to the Banff criteria. •Time to first BCAR episode. •Type and severity of any BCAR episodes according to the Banff criteria. •Incidence and grade of TEAEs, including SAEs. •Incidence of opportunistic infections, specifically BK virus (BKV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation •Incidence of neoplasia. •Proportion of subjects who are receiving tacrolimus monotherapy at Week 84. •Cumulative dose of immunosuppression, including but not limited to mycophenolic acid (MPA)/mycophenolate mofetil (MMF) and tacrolimus through to Week 84. •Presence of CD4 RNA transcript positive cells that are also positive for HLA-A2 CAR RNA transcripts in the renal transplant biopsy at Week 16. •Incidence and severity of chronic graft dysfunction, as measured by estimated glomerular filtration rate (eGFR). •Incidence and severity of chronic graft dysfunction, as measured by the Banff criteria for chronic rejection including the Banff lesion score inflammation in area of interstitial fibrosis and tubular atrophy (i-IFTA). •Incidence of graft loss due to rejection. •Incidence and (semi-quantitative) intensity of de novo DSA.;Timepoint(s) of evaluation of this end point: The timepoint of evaluation of each secondary endpoint is given in the section above (E.5.2). | — |
Countries
Netherlands, United Kingdom
Contacts
Public ContactTX200-KT02 Information Desk
Sangamo Therapeutics France SAS
Outcome results
None listed