Allograft rejection Renal transplant rejection
Conditions
Interventions
See section 7.1 in the protocol (page 71-75).
The investigational medicine (TX200 TR101) is an autologous gene therapy
medicinal product composed of Treg (CD4+/CD45RA+/CD25+/CD127low/neg) that have
Sponsors
Sangamo Therapeutics France SAS
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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. Normal or non-clinically significant abnormality in the electrocardiogram (ECG), at investigator*s discretion. 6. Women who are of childbearing potential must have a negative serum pregnancy test at screening and before transplantation. 7. 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) 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. 4. Subjects that have a transplant planned or scheduled for at least 10 weeks after the time of enrolment. Inclusion Criteria (All Transplant Donors) 1. Willing and able to provide written IC in accordance with local regulations and governing IEC/IRB requirements prior to any procedure or evaluation performed specifically for the sole purpose of the study. 2. Aged at least 18 years on the day of signing the IC form. 3. ABO blood type compatible with the organ recipient. 4. Negative serology for HIV, HBV, HCV and syphilis. 5. Willing to provide personal and medical/biological data and samples for the study analysis. Additional Inclusion Criterion (Transplant Donors for Transplant Recipients to be Administered TX200 TR101 Only) 1. HLA-A*02 positive typing.
Exclusion criteria
Exclusion criteria: Exclusion Criteria (All Transplant Recipients) 1. HLA identical to the prospective organ donor. 2. Subjects with prior organ transplant. 3. Known hypersensitivity to study medication ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalisation. 4. Known hypersensitivity or contraindications for anti-thymocyte globulin (ATG), tacrolimus or mycophenolic acid (MPA)/ mycophenolate mofetil (MMF). 5. Positive serology for human immunodeficiency virus (HIV) or syphilis. 6. Evidence of active or occult hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. 7. Subjects who are Epstein-Barr Virus (EBV) seronegative. 8. Positive flow cytometric crossmatch using donor lymphocytes (T and B cells) and recipient serum. 9. Subjects with panel-reactive antibody (PRA) >20% within 6 months prior to enrolment. 10. Subjects with current, recent or historical donor-specific antibodies. 11. Previous treatment with any desensitisation procedure (with or without intravenous immunoglobulin) 12. Subjects with underlying renal disease with a high risk of disease reoccurrence in the transplanted kidney including primary focal segmental glomerulosclerosis, C3 glomerulopathy, types I or II membranoproliferative glomerulonephritis or haemolytic-uraemic syndrome (HUS), including a typical HUS. If the subject has ESRD of unknown aetiology and/or has no histologically confirmed diagnosis the subject may be enrolled into the study if there are no clinical, laboratory, histological or genetic features suggestive of a diagnosis of primary focal segmental glomerulosclerosis, types I or II membranoproliferative glomerulonephritis, C3 glomerulopathy, or HUS, including atypical HUS, as deemed by the investigator. 13. Concomitant clinically active local or systemic infection. 14. Use of any experimental medicinal product within 3 months or 5 half-lives prior to the screening visit, whichever is longer, and agreement to not take any experimental medicinal product throughout the trial. 15. Subjects who are currently receiving systemic immunosuppressive agents (e.g., methotrexate, infliximab, adalimumab, corticosteroids) for other indications such as autoimmune diseases, or subjects with comorbidities for which treatment with such agents are likely during the study, with the following exception: • Subjects who are receiving or may require short-term and/or low dose (e.g., prednisone or prednisone equivalent < 5 mg daily) or methotrexate (e.g. 15 mg weekly) courses of corticosteroids are not precluded from enrolment, at the discretion of the investigator in consultation with the Sponsor*s Medical Monitor. 16. Clinical evidence of significant unstable or poorly controlled acute or chronic diseases (i.e., cardiovascular, pulmonary, haematologic, gastrointestinal, hepatic, neurological, 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. • Subjects who, at the discretion of the investigator, are deemed at high risk of a renal thrombotic event. 17. Subjects with current or previous history of clinically relevant central nervous system pathology (including but not limited to seizures within the las
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary: - Incidence and grade of TEAEs, including SAEs, within 28 days post TX200 TR101 infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary: Clinical From the day of TX200-TR101 infusion through to Week 84: - 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. From the day of TX200-TR101 infusion through to Week 84: - Incidence and grade of TEAEs, including SAEs. - Incidence of opportunistic infections, specifically BKV, EBV and 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 MPA/MMF and tacrolimus through to Week 84. Key Secondary: Biomarkers - 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. Other Secondary: Clinical From the day of TX200-TR101 infusion through to Week 84: - Incidence and severity of chronic graft dysfunction, as measured by eGFR. - Incidence and severity of chronic graft dysfunction, as measured by the Banff criteria for chronic rejection including the Banff lesion score i-IFTA. - Incidence of graft loss due to rejection. - Incidence and (semi-quantitative) intensity of de novo DSA. Exploratory: Clinical - Changes from baseline in laboratory parameters, 12-lead ECG and vital signs from the day of TX200-TR101 infusion through to Week 84. - Incidence of hypertension, dyslipidaemia and new onset diabetes at Week 60 and Week 84 after transplantation. - Absolute value and change from baseline in SF 36v2® through to Week 84. Exploratory: Biomarkers - Proportion of CD4 RNA transcript positive cells that are also positive for HLA-A2 CAR RNA transcripts in the renal transplant biopsy at Week 16, Week 36 and Week 60 (if available). - Proportion of other RNA transcript positive and negative cells in the renal transplant biopsy at Week 16, Week 36 and Week 60 (if available). - Levels and changes from baseline in b | — |
Countries
Netherlands
Outcome results
None listed