E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
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 |
Primary Objective: 1) To examine the safety of Treg therapy together with tocilizumab and donor bone marrow in living donor kidney transplant recipients. 2) To assess chimerism levels within the first month post-transplant.
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E.2.2 | Secondary objectives of the trial |
To demonstrate that the study protocol allows the initiation of a step-wise reduction of immunosuppression up to a point when patients receive drug monotherapy. To gain insight as to whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation. To assess the frequency of biopsy-proven acute rejection episodes. To assess the frequency of subclinical rejection episodes on surveillance biopsies. To assess kidney graft function. To assess the area-under-the-curve (AUC) of chimerism. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient has provided written informed consent. Patient is 18 years or older. Patient is a planned recipient of a living donor kidney transplant. Patient is a planned recipient of an ABO-compatible kidney graft. Patient is a planned recipient of a kidney graft from a donor that is not HLA-identical. Patient is negative for DSA. WOCBP must have a negative pregnancy test at inclusion. WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized. |
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E.4 | Principal exclusion criteria |
Patient is EBV-negative on serology. Patient is HIV-positive or suffering from chronic viral hepatitis. Patient is CMV-negative and receiving a kidney from a CMV-positive donor. Positive T-cell lymphocytotoxic cross match. Patient with prior kidney transplant or non-renal solid organ transplant. Patient has a known contraindication to any of the protocol-specified treatments. Patient had been diagnosed with a malignancy within 5 years prior to study entry, excluding non-metastatic basal or squamous cell carcinoma of the skin. Female patients who are breast-feeding. Female patients with a positive pregnancy test |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary endpoint 1 (safety) is defined as incidence of GVHD, impaired graft function [eGFR <35mL/min/1.73m2] or patient death, whichever occurs first, within 12 months post-transplant. Co-primary endpoint 2 (efficacy) is defined as the individual peak chimerism levels within the first month post-transplant. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Co-primary endpoint 1: Within the first 12 months post-transplant. Co-primary endpoint 2: Within the first month post- transplant. |
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E.5.2 | Secondary end point(s) |
To demonstrate that the study protocol allows the initiation of a step-wise reduction of immunosuppression up to a point when patients receive drug monotherapy. To gain insight as to whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation. To assess the frequency of biopsy-proven acute rejection episodes. To assess the frequency of subclinical rejection episodes on surveillance biopsies. To assess kidney graft function. To assess the area-under-the-curve (AUC) of chimerism. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Within the first 12 months post-transplant, and within the long-term extension phase (optional; phase 1: 12-36 months post-transplant, phase 2: 36-60 months post-transplant). |
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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 | No |
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 | No |
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 | No |
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 | Yes |
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.8.5 | 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 | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |