A Phase I/IIa Study to Evaluate the Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (TX200-TR101) in Living Donor Renal Transplant Recipients

Phase 1

• Conditions: 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: 21.1Level: LLTClassification code 10050436Term: Prophylaxis against renal transplant rejectionSystem Organ Class: 100000004865; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2019-001730-34-NL
• Lead Sponsor: Sangamo Therapeutics France SAS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-25
• Last Update Posted: 10 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 42

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 (see Appendix 2) 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.

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 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)
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 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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 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.
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) 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 (e.g., 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, stroke, severe brain injury, cerebellar disease or CNS vasculitis).
18. Current or previous history within the last 5 years of malignancy, with the following exceptions:
• Subjects with any previous history of haematological malignancy are precluded from enrolment.
• Subjects who have had non-melanoma skin cancer or cervical carcinoma in situ that have been successfully treated with no evidence of recurrence are not precluded from enrolment.
19. Subjects whose life expectancy is severely limited by disease state other than renal disease.
20. Subjects with a history of substance abuse (drug or alcohol) within the past 2 years or that is considered not compatible with adequate study follow-up, or psychiatric disorder or other condition that is not compatible with adequate study follow-up.
21. Subjects with laboratory values that meet th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified