A Multicentre, Open-Label, Single Ascending Dose, Dose-Ranging, 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.
- Conditions
- 1002766510029149Allograft rejectionRenal transplant rejection
- Registration Number
- NL-OMON56213
- Lead Sponsor
- Sangamo Therapeutics France SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 8
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 (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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary:<br /><br>- Incidence and grade of TEAEs, including SAEs, within 28 days post TX200 TR101<br /><br>infusion.</p><br>
- Secondary Outcome Measures
Name Time Method