Patients after renal transplantation with signs of drug intolerance to their immunsuppressive therapy are considered to be converted to Nulojix MedDRA version: 14.1 Level: PT Classification code 10038533 Term: Renal transplant System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 14.1 Level: PT Classification code 10054980 Term: Immunosuppressant drug therapy System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Nulojix 250mg
Pharmaceutical Form: Lyophilisate for solution for infusion
Trade Name: Prograf 1 mg
Pharmaceutical Form: Capsule, hard
Trade Name: Prograf 0.5 mg
Pharmaceutical Form: Caps
Sponsors
Charité, Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a.Renal transplant recipients, whose received renal allograft at least 3 months prior to inclusion b.Patients on a CNI- or mTORi-based therapy for more than 3 months, who have signs of CNI- or mTORi related toxicity or intolerance and are converted due to clinical indication to a CNI- and mTORi-free immunosuppression with Belatacept c.Patients with acceptable renal function and a serum creatinine =4 mg/dl. d.Patient must have received primary or secondary renal allograft from a deceased donor or living donor from a compatible (A, B, AB or O) blood type e.Patients with low to standard immunological risk, who had a PRA 18 years h.Women of childbearing potential (WOCBP) must be using two adequate methods of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drug to minimize the risk of pregnancy. i.WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: j.Amenorrhea that has lasted for ? 12 consecutive months without another cause, or k.For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. l.Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. m.WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of the investigational product. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: a.WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug. b.Women who are pregnant or breastfeeding. c.Women with a positive pregnancy test. d.Sexually active fertile men not using effective birth control if their partners are WOCBP. e.Multi-organ recipients (solid organ or bone marrow) f.Patients who suffered from severe rejection (= Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within 6 months of enrolment in this study. g.Patient with malignancies with the exception of local, noninvasive, fully excised: cutaneous basal cell carcinoma or cutaneous squamous cell carcinoma h.Patients, who – according to the investigator – require for medical reasons continued therapy with CNI or mTORi i.Subjects who have a negative or unclear serology concerning Epstein –Barr-Virus (EBV) j.Treatment with any investigational drug within 3 months preceding the study k.Prisoners, or subjects who are involuntarily incarcerated. l.Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine cellular and transcriptional Biomarker candidates of the humoral and cellular immune system that elucidate the effect of Nulojix in preventing DSA formation after conversion in comparison to a CNI- or mTORi-based therapy in renal transplant recipients. ;Secondary Objective: To determine overall safety, efficacy and tolerability of Nulojix after conversion in comparison to a CNI- or mTORi-based therapy in renal transplant recipients. In detail: ;Primary end point(s): Significant changes of - relative and absolute numbers of B-cells, especially memory B-cells, Plasma blasts and Plasma cells - relative and absolute numbers of T-helper, effector, central memory T-cells and regulatory T cells - of mRNA and micro RNA expression profiles ;Timepoint(s) of evaluation of this end point: 3, 6 and 12 months after conversion form standard immunsuppressive therapy to Nulojix | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - changes in expression of established biomarkers of renal failure (NGAL, KIM-1, IP-10 and Calprotectin) - Incidence and time to death or graft failure within - Overall safety and tolerability including incidence of Adverse events (Aes), Serious adverse events (SAEs) after baseline - Change of estimated renal function (eGFR) - The change in eGFR will be determined between patients that were converted to Belatacept and the control group stratified according to the use of CNI or mTORi immunosuppression at baseline. - Comparison of the incidence of patients with improved renal function (according to CKD-EPI-formula) - Incidence of biopsy proven rejection (BPAR; Banff grade =IA) - Proportion of severity grades of the first episode of BPAR (Banff grade) - Development of de novo donor specific antibodies - Development of proteinuria - Estimation of cardiovascular risk via the cardiovascular risk calculator - Changes of blood pressure and and cardiovascular risk factors including lipids, and diabetes - changes of cardial hypertrophy, heart congestion failure and ejection fraction by echocardiography - Incidence of NODAT (New onset of diabetes mellitus after transplantation) - Incidence of any malignancy - Incidence of infections, serious or opportunistic infection (CMV, BK-virus) - Incidence and time to CMV-, BK-Virus and EBV viremia - Incidence of premature discontinuation of assigned treatment with Nulojix, as confirmed by the investigator for any reason. - Changes concerning quality of life and medication adherence via Questionnaires ;Timepoint(s) of evaluation of this end point: 3, 6 and 12 months after conversion form standard immunsuppressive therapy to Nulojix | — |
Countries
Germany
Contacts
Public ContactClinical Trial informations
Charité Universitätsmedizin Berlin
Outcome results
None listed