Prospective Donor Specific T Response Measurment for IS Minimization in de Novo Renal Transplantation

Prof. Dr. Petra Reinke

Status: Completed

Conditions: Effects of Immunosuppressant Therapy; Disorder Related to Renal Transplantation

Treatments: Drug: MMF (mycophenolate mofetil) (for Group B); Drug: Mycofenolate mofetil (MMF) (for Group A); Drug: 6-methyl prednisolone (Steroids) (for Group A); Drug: Tacrolimus (for Group B); Drug: Tacrolimus (for Group A); Drug: 6-methyl prednisolone (Steroids) (for Group B)

Study type: Interventional

Funder types: Other

Identifiers

NCT02540395

2014-001325-33 (EudraCT Number)

CELLIMIN

Details and patient eligibility

About

The main objective of the study is to demonstrate the utility and safety of the IFN-γ (Interferon Gamma) ELISPOT (Enzyme-linked immunosorbent spot) marker for the stratification of kidney transplant recipients into low and high IS (Immunosuppression) regimens. The enrichment study will test non-inferiority of low IS regimen compared to high IS regimen, assuming 10% of BPAR at 6-months in the control group, and allowing a non-inferiority limit of maximum 10%.

Enrollment: 184 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Men and women, age ≥18 years.
2. Subject must be a recipient of a first renal transplant from a deceased or living donor.
3. Subject must have a current documented PRA (Panel of reactive antibodies) <20% and no detectable anti-class I and II HLA (human leukocyte Antigens) antibodies by solid phase assay (Luminex®).
4. Subject is willing to provide signed written informed consent.
5. 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 (Human chorionic gonadotropin)) within 72 hours prior to the start of clinical trial.

Exclusion criteria

1. Subjects undergoing renal transplant with a current documented PRA >20% and/or detectable anti-class I and II HLA antibodies by solid phase assay (Luminex®).

2. CDC (complement dependent cytotoxicity) positive cross match.

3. Subjects receiving an allograft from a donor older than 65 years with elevated creatinine levels and/or treated diabetes.

4. Cold ischemia time (CIT) higher than 24h.

5. Subjects with a prior solid organ transplant (SOT), including renal re-transplantation, or receiving a concurrent SOT.

6. Patients previously treated with daclizumab or basiliximab.

7. Subjects with underlying renal disease of:

   • Primary focal segmental glomerulosclerosis.
   • Type I or II membranoproliferative glomerulonephritis
   • Atypical Haemolytic uremic syndrome (HUS) / thrombotic thrombocytopenic purpura syndrome.

8. Subject with Hepatitis B chronic infection and/or active infection by Hepatitis C virus (positive PCR (polymerase chain reaction result) at the moment of transplant.

9. Subjects with known human immunodeficiency virus (HIV) infection.

10. Patients with active systemic infection that requires the continued use of antibiotics.

11. Patients with neoplasia except localized skin cancer receiving appropriate treatment.

12. Patients with severe anemia (hemoglobin < 6g/dl), leucopenia (WBC (White blood cells) <2500/mm3), thrombocytopenia (platelets <80.000/mm3).

13. Hemodynamically instable patients even if their hemoglobin level counts > 6 g/dl.

14. Patients with intestinal pathology or severe diarrhoea that can hinder absorption according to medical criteria.

15. Subjects with a known hypersensibility to any of the drugs used in this protocol.

16. Subjects who have used any investigational drug within 30 days prior to enrolment in this clinical trial.

17. 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.

18. Subjects who are legally detained in an official institution

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

184 participants in 2 patient groups

Group A: Standard of care

Active Comparator group

Description:

Standard of care immunosuppressive regimen based on TAC (Prograf) (achieving 4-8ng/ml trough levels), MMF (Cellcept, Myfortic, Myfenax)(1gr bid) and steroids (6-methyl prednisolone, Urbason, Methypred) (according to KDIGO guidelines). All patients in group A recieve the tripple-drug IS as suggested by guidelines. In case of rejection the patients are treated with high dosage of Methypred and/or Thymoglobuline

Treatment:

Drug: Tacrolimus (for Group A)

Drug: 6-methyl prednisolone (Steroids) (for Group A)

Drug: Mycofenolate mofetil (MMF) (for Group A)

Group B: "Low" Immunosuppression regimen

Experimental group

Description:

(based on TAC monotherapy (Prograf) to achieve 8-10 ng/ml trough levels during the first 4 weeks after transplantation and 6-8 ng/ml thereafter, MMF (Cellcept, Myfortic, Myfenax) (1g bid) during the first 7 days post-transplant and stopped thereafter) and steroids (6-methyl prednisolone; Urbason, Methypred) (tapering until discontinuation on month 2 post-transplant). In contrast to Group A the patients are treated with a two drug IS combination consisting of Prograf and Methypred. In case of rejection the patients are treated with hifg dosage of Methypred and/or Thymoglobuline.

Treatment:

Drug: 6-methyl prednisolone (Steroids) (for Group B)

Drug: Tacrolimus (for Group B)

Drug: MMF (mycophenolate mofetil) (for Group B)