E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rejection rate, graft loss or poor graft function defined as eGFR<40 ml/min in patients with kidney transplantation. |
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E.1.1.1 | Medical condition in easily understood language |
Rejection rate, graft loss or poor function in patients with kidney transplantation. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
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 |
1) Composite endpoint of efficacy failure of the induction regimen defined as occurrence of any of the following individual outcomes up to 12 months post transplantation (start of follow up at transplantation): acute rejection, graft loss or poor graft function defined as eGFR<40 ml/min. |
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E.2.2 | Secondary objectives of the trial |
1) Prevalence of biomarker signatures of rejection and tolerance at 6 and 12 months 2) Incidence of death by 12 months post-transplantation 3) Incidence of graft loss by 12 months post-transplantation 4) Incidence of metabolic and cardiovascular co-morbidity by 12 months post-transplantation (post-transplant diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, stroke, peripheral vascular disease) 5) Proportion of subjects who remain on tacrolimus/steroids therapy at 12 months post-transplantation 6) Incidence of acute and chronic lesions assessed by the Banff 07 score in protocol biopsy at 12months post-transplantation 7) Incidence of discontinuation of study treatment 8) DSA at 12M 9) Overall safety of tacrolimus/steroids therapy immunosuppressive regimen defined as viral and bacterial infections, malignancies and autoimmunity. 10) Health-related quality of life using EQ5D-5L and SF-36v2 questionnaires at baseline, M1, M3, M6, and M12
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Primary deceased-donor or living-donor kidney transplantation 2. Men and women (recipient) age >18 years and <70 years 3. Panel reactive antibody frequency/ calculated panel reactive antibody frequency (peak PRA/cPRA) <20% 4. Written informed consent 5. Diagnosis of end stage renal disease 6. Women of Childbearing Potential (WOCBP) must be using a highly effective method of contraception (Pearl-Index < 1) to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL]. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of clinical trial. Male participants with pregnant or non-pregnant WOCBP partner must use condoms. |
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E.4 | Principal exclusion criteria |
1. Previous transplantation 2. Combined kidney transplantation with other organ 3. Subjects receiving an allograft from a donor older than 65 years. 4. Immunosuppressive therapy up to 6 months before transplantation 5. Planned induction therapy with depletion agents 6. EBV seronegativity 7. HIV positivity 8. Leukopenia < 3000 cells per microliter, thrombocytopenia < 100 000 cells per microliter 9. Biological therapy history with ATG, OKT3, anti TNF agents 10. Tuberculosis history 11. Cancer history (skin non-melanoma cancer excluded) 12. Anti HCV positivity, HBsAg positivity or HBV DNA positivity 13. Detectable donor specific antibodies (DSA) by solid phase assay (Luminex®) 14. Subjects with a known hypersensibility to any of the drugs used in this protocol 15. Subjects who have used any investigational drug within 30 days prior to enrolment in this clinical trial 16. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, women who are pregnant or breastfeeding or women with a positive pregnancy test on enrolment 17. Subjects who are legally detained in an official institution 18. All contraindications against study medication (including auxiliary substances) 19. Interactions with study medication 20. Current treatment with one of the following substances: cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, rituximab, prednisone 21. Patients unwilling to consent to saving and propagation of pseudonymized medical data and/or biological samples for study reasons 22. Chronic heart failure (NYHA III, IV) at transplantation 23.Participation in other clinical trials (pharmaceutical trials) 24. persons dependent of the sponsor, investigator or investigative site 25. positive Quantiferon test (for TBC) 26. live vaccine treatment 30 days prior to enrolment in this clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Composite endpoint of efficacy failure of the induction regimen defined as occurrence of any of the following individual outcomes up to 12 months post transplantation (start of follow up at transplantation): acute rejection, graft loss or poor graft function defined as eGFR<40 ml/min. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 12 months post transplantation. |
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E.5.2 | Secondary end point(s) |
1) Prevalence of biomarker signatures of rejection and tolerance at 6 and 12 months 2) Incidence of death by 12 months post-transplantation 3) Incidence of graft loss by 12 months post-transplantation 4) Incidence of metabolic and cardiovascular co-morbidity by 12 months post-transplantation (post-transplant diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, stroke, peripheral vascular disease) 5) Proportion of subjects who remain on tacrolimus/steroids therapy at 12 months post-transplantation 6) Incidence of acute and chronic lesions assessed by the Banff 07 score in protocol biopsy at 12months post-transplantation 7) Incidence of discontinuation of study treatment 8) DSA at 12M 9) Overall safety of tacrolimus/steroids therapy immunosuppressive regimen defined as viral and bacterial infections, malignancies and autoimmunity. 10) Health-related quality of life using EQ5D-5L and SF-36v2 questionnaires at baseline, M1, M3, M6, and M12 11) Assessment of patient-specific resource consumption using a trial specific questionnaire at initial discharge, M3, M6, M12, and in cases of repeated hospitalization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) at 6 and 12 months 2) up to 12 months 3) up to 12 months 4) up to 12 months 5) at 12 months 6) at 12 months 7) up to 12 months 8) at 12 months 9) up to 12 months 10) at baseline, 1 month, 3 months, 6 months and 12 months 11) at Initial discharge, 3 months, 6 months and 12 months |
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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 | No |
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 | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |