TREG02 for Kidney transplantation

Inclusion criteria

• {"criterion_text":"- Chronic renal insufficiency with a GFR < 15 ml/min x 1.73 m², accepted by the organ transplantation conference, registered by ET (Eurotransplant; www.eurotransplant.org)"}
• {"criterion_text":"- Age: 18 – 70 years of age"}
• {"criterion_text":"- Willing and able to participate in the trial"}
• {"criterion_text":"- Signed and dated written informed consent.* (*For patients unable to read and/or write, an oral informed consent observed by an independent witness is acceptable, if the patient has fully understood the oral information given by the Investigator. The witness should sign the consent form on behalf of the patient.)"}
• {"criterion_text":"- Haematology: Hb ≥7.0 g/dl; platelets ≥80x10^9/l; total leukocyte count: ≥3.0x10^9/l"}
• {"criterion_text":"- Karnofsky score: 40 – 90"}
• {"criterion_text":"- Donor eligibility criteria: Individuals 18 years of age or more are eligible as donors. However, potential donors >50 years will be not eligible if they have more than 2 of the following risk factors; hypertension or serum creatinine >1.5 mg/dl at the time of explantation or an anticipated cold ischemia time of >24 h."}

Exclusion criteria

• {"criterion_text":"- Patient has previously received any tissue or organ transplant other than the planned kidney graft"}
• {"criterion_text":"- Female patients who are breast-feeding"}
• {"criterion_text":"- All female patients of childbearing age* unless the patient is willing to maintain a highly effective method of birth control** for the duration of the study"}
• {"criterion_text":"- Known contraindication to protocol-specified treatments / medications"}
• {"criterion_text":"- AL amyloidosis with significant extrarenal involvement"}
• {"criterion_text":"- Decompensated cirrhosis"}
• {"criterion_text":"- Severe irreversible obstructive or restrictive lung disease"}
• {"criterion_text":"- Severe uncorrectable and symptomatic cardiac disease that is deemed by cardiologists to preclude transplantation"}
• {"criterion_text":"- Progressive central neurodegenerative disease"}
• {"criterion_text":"- Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule"}
• {"criterion_text":"- Any form of drug or alcohol abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel"}
• {"criterion_text":"- HIV-positive or suffering chronic viral hepatitis"}
• {"criterion_text":"- Patients unable to give their informed consent (e.g. patients under legal guardianship)"}
• {"criterion_text":"- Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities"}
• {"criterion_text":"- Known allergy/hypersensitivity to any component of the study product"}
• {"criterion_text":"- Positive SARS-CoV-2 RT-PCR test"}
• {"criterion_text":"- Persons who demonstrate dependency from the sponsor, investigator or trial site"}
• {"criterion_text":"- Panel-reactive antibodies (PRA) grade > 20% within last 6 months before enrolment"}
• {"criterion_text":"- Previous treatment with any desensitization procedure with or without intravenous immunoglobulin"}
• {"criterion_text":"- Concomitant malignancy or history of malignancy within 5 years prior to study inclusion in the trial (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin or curatively treated renal cell carcinoma with complete nephrectomy)"}
• {"criterion_text":"- Evidence of significant local or systemic infection"}
• {"criterion_text":"- EBV-negative recipient receiving a kidney from an EBV-positive deceased-donor"}
• {"criterion_text":"- Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN (Upper Limit of Normal range)"}
• {"criterion_text":"- Malignant or pre-malignant haematological conditions. Multiple myeloma, light or heavy chain deposition disease"}
• {"criterion_text":"- Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives"}
• {"criterion_text":"- Any condition which, according to the PI, would place the subject at undue risk"}
• {"criterion_text":"- Ongoing treatment with systemic immunosuppressive drugs at study entry"}
• {"criterion_text":"- Participation in another clinical trial during the study or within 5 times as the half-life time of the drug used in the previous trial prior to planned study entry"}
• {"criterion_text":"- Female patients of childbearing age with a positive pregnancy test at enrolment"}

Primary endpoints

• {"endpoint_text":"- Primary safety endpoint 1: Acute toxicity associated with infusion of Treg02, assessed by evidence of: (a) pulmonary complications, (b) immunological reactions resulting in anaphylactic reactions, immediate cardiovascular compromise or other acute organ failure, (c) Treg therapy associated biochemical perturbation (significant deviations in biomarker data) as assessed by the immunological impact of the infused cells or apoptosis of Tregs and release of cellular contents.","definition_or_measurement_approach":"Acute toxicity assessed by clinical evidence of pulmonary complications, immunological anaphylactic reactions or immediate cardiovascular compromise, other acute organ failure, and significant deviations in biomarker data indicating cellular perturbation."}
• {"endpoint_text":"- Primary safety endpoint 2: Over-suppression of the immune system by assessing evidence of: (a) major and/or opportunistic infections, especially increased frequency of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and polyomavirus reactivation and/or disease, (b) early development of neoplasia","definition_or_measurement_approach":"Assessment of incidence and severity of major/opportunistic infections (notably CMV, EBV, polyomavirus) and monitoring for development of neoplasia."}
• {"endpoint_text":"- Primary safety endpoint 3: Chronic toxicity associated with Treg02 infusions, measured by evidence of: (a) malignancies arising directly from adoptive cellular therapy, (b) autoimmune disorders, (c) inflammatory pathologies, (d) anaemia, cytopenia or biochemical anomalies unrelated to the transplanted kidney functions","definition_or_measurement_approach":"Long-term monitoring for malignancies, autoimmune disorders, inflammatory pathologies, hematologic or biochemical abnormalities not attributable to the transplanted kidney."}
• {"endpoint_text":"- Primary clinical endpoint: Biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation","definition_or_measurement_approach":"Biopsy-confirmed acute rejection events occurring within 60 weeks post-transplantation, diagnosed by histology (BCAR)."}

Secondary endpoints

• {"endpoint_text":"- Secondary indices of efficacy 1: Prevention of acute rejection (a): time to first acute rejection, b): severity of acute rejection episodes based on response to treatment and histological scoring, c): level of total immunosuppression at the final trial visit)","definition_or_measurement_approach":"Measures include time-to-first acute rejection, severity based on treatment response and histological scoring, and total immunosuppression level at final visit."}
• {"endpoint_text":"- Secondary indices of efficacy 2: Incidence of patients treated for subclinical acute rejection based on histopathological findings","definition_or_measurement_approach":"Incidence of patients receiving treatment for subclinical rejection determined by histopathology."}
• {"endpoint_text":"- Secondary indices of efficacy 3: Prevention of chronic graft dysfunction (chronic rejection or interstitial fibrosis/tubular atrophy) assessed by clinically impaired glomerular filtration rate (GFR) and histopathological (Banff staging) criteria measures","definition_or_measurement_approach":"Assessment of chronic graft dysfunction via GFR measures and Banff histopathological staging for interstitial fibrosis/tubular atrophy."}
• {"endpoint_text":"- Secondary indices of efficacy 4: Incidence of post-transplant dialysis, inclusion on the transplant waiting list, or re-transplantation following graft loss through rejection (acute or chronic)","definition_or_measurement_approach":"Incidence of graft loss outcomes including need for dialysis, relisting for transplant, or re-transplantation."}
• {"endpoint_text":"- Secondary indices of efficacy 5: Reduced incidence of adverse events/rejections following tapering of immunosuppression (e.g. cardiovascular complications, drug toxicity, etc.)","definition_or_measurement_approach":"Comparison of adverse event/rejection rates following immunosuppression tapering."}
• {"endpoint_text":"- Biomarker panel: measure functional and molecular indices reflecting the immune response as well as treatment safety and efficacy of regulatory T cells","definition_or_measurement_approach":"Measurement of functional and molecular biomarkers reflecting immune response, safety and efficacy (immunomonitoring/biomarker analyses)."}
• {"endpoint_text":"- Quality-of-life using the SF-12 QoL health survey","definition_or_measurement_approach":"Patient-reported quality-of-life measured using the SF-12 questionnaire."}

Germany

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

587

Number Of Sites

1

Number Of Participants

27

Primary sponsor

Full Name

Charite Universitaetsmedizin Berlin KöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Contract research organisations

Name

SCIRENT Clinical Research and Science GmbH

Responsibilities

Monitoring and Pharmacovigilance

Name

CheckImmune GmbH

Responsibilities

Immunomonitoring / Biomarker panel analyses

Third parties

• {"country":"Germany","full_name":"CheckImmune GmbH","duties_or_roles":"Immunmonitoring/ Biomarker panel analyses","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"SCIRENT Clinical Research and Science GmbH","duties_or_roles":"Monitoring and Pharmacovigilance","organisation_type":"Pharmaceutical company"}