E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Renal (allograft) transplant |
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E.1.1.1 | Medical condition in easily understood language |
Patients who have received a kidney transplant (organ from another person) |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050436 |
E.1.2 | Term | Prophylaxis against renal transplant rejection |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In patients who have received a kidney transplant, can the administration of TR001 T regulatory cell product 6-months following a kidney transplant allow minimization of maintenance immunosuppression to a single immunosuppressive drug(tacrolimus) without an increase in transplant rejection rates compared to standard treatment (tacrolimus and mycophenolate mofetil)? |
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E.2.2 | Secondary objectives of the trial |
To collect evidence on the safety and additive benefits of TR001 T regulatory cell therapy and reduced immunosuppression compared to standard treatment. This will include time to first transplant rejection episode, severity of rejection episodes, incidence of transplant loss as a result of rejection, kidney transplant function at the end of trial, incidence of serious infections, incidence of cancer, incidence of biochemical or blood count disturbances, and both transplant and patient survival.
There is a further exploratory objective of the study, which is designed to monitor the patient's immune system post transplant using a panel of novel markers in the patient's blood. In the future this may help identify patient's who are particularly suitable for immunosuppression reduction, or detect rejection before it is clinically obvious. This data will not be be used for clinical care of patients during this trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Kidney Donor:- - aged at least 18 - ABO blood group compatible with the recipient - eligible for live kidney donation - willing and able to give informed consent for participation in the trial
Kidney Recipient - Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor - Willing and able to give informed consent for participation in the trial - Aged over 18 years
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E.4 | Principal exclusion criteria |
Kidney Donor - Participation in another interventional clinical trial during the study or within 28 days prior to planned study entry - Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may invalidate communication with the investigator and/or designated personnel
Kidney Recipient
• The potential participant has previously received any other type of tissue or organ transplant • Known contraindication to the protocol-specified treatments or medications • ABO blood group incompatible with donor • Calculated reaction frequency (CRF) of >40% within 6 months prior to transplant • Previous treatment with any desensitisation procedure (with or without IVIg) • Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully treated non-metastatic basal or squamous cell carcinomas of the skin) • Serologically positive for anti-HIV-1/2 Ab, HbsAg, anti-HBcAb, antiHCV Ab, anti-HTLV-1/2 Ab or syphilis (treponema palladium) • Significant liver disease, defined as persistently elevated ALT levels >3 x upper limit of normal range (ULN) • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial • Participation in another interventional clinical trial during the study or within 28 days prior to planned study entry • Female participant who is pregnant, lactating or planning pregnancy during the course of the trial • Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule • Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may invalidate communication with the investigator and/or designated personnel
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of biopsy-confirmed acute rejection (BCAR) in the 6 to 18-month period post-transplantation, between groups. Histopathological grading of biopsy material will be performed according to the Banff criteria. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6- to 18-month period post transplantation. |
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E.5.2 | Secondary end point(s) |
Secondary and exploratory objectives will be assessed as: 1. Indicators of influence of Treg administration on transplant outcome 2. Markers of over-suppression of the immune system 3. Signs of chronic toxicity associated with infusion of cell products 4. Utility of immune monitoring (IM) will be examined using a novel panel of immunological laboratory assays
1. Indicators of influence of Treg administration on transplant outcomes will include: 1.A. Impact on acute rejection o Time to first acute rejection episode o Severity of acute rejection episode based on response to treatment and histological scoring o Total immunosuppressive burden at the final trial visit o Incidence of graft loss through rejection
1.B. Success in reduction of immunosuppression o Proportion of patients on tacrolimus monotherapy at end of study
1.C. Prevention of chronic graft dysfunction o Chronic allograft dysfunction or interstitial fibrosis/tubular atrophy (IF/TA) assessed by clinical (impairment of eGFR) and histopathological (Banff staging) measures
1.D. Avoidance of drug-related complications by immunosuppressant reduction o Incidence of drug-related adverse events
1.E. Patient survival
2. Markers of over-suppression of the immune system will include: 2.A. Incidence of serious and/or opportunistic infections (especially CMV, EBV and polyoma (BK) virus) 2.B. Incidence of neoplasia
3. Signs of chronic toxicity associated with infusion of cell products will include: 3.A. Incidence of auto-immune disorders 3.B. Incidence of anaemia, cytopaenias, or biochemical disturbances unrelated to the function of the transplanted kidney
4. Immune monitoring will include: 4.A. Flow cytometric cell phenotype analysis using standardised immune monitoring panels developed in conjunction with Beckman Coulter 4.B. T cell functional assays against donor and third-party antigen including CD154/CD137 ratio analysis 4.C. Serum cytokine analysis and metabolic profiling 4.D. Gene expression and RNA sequencing analyses including a Treg-Specific Demethylated Region (TSDR) analysis and T-Cell Receptor Sequencing
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary outcomes will be assessed continuously during the 18 months post-transplant, with data collected at study visits and any episodes of adverse, or serious adverse events as they arise. A schematic of the tests by study visit is given in tables 1 and 2 in the study protocol.
Histopathological samples will be taken at 5 and 9 months (protocol biopsies). Any other biopsies performed during follow-up will be at the discretion of the responsible clinician and will be deemed ‘for-cause’. These will be reviewed and reported by the study pathologist using the Banff criteria.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immune response monitoring |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |