Biomarker after conversion to belatacept mediaction in comparison to standard therapy in renal transplant patients.

• Conditions: Patients after renal transplantation with signs of drug intolerance to their immunsuppressive therapy are considered to be converted to Nulojix; MedDRA version: 14.1Level: PTClassification code 10038533Term: Renal transplantSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 14.1Level: PTClassification code 10054980Term: Immunosuppressant drug therapySystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2012-005652-42-DE
• Lead Sponsor: Charité, Universitätsmedizin Berlin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-12
• Last Update Posted: 26 November 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 <30% before transplantation
f.Patients with concomitant immunosuppression with MPA (=1g/d MMF or =720 mg/d EC-MPS)
g.Age >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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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. <br>;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. <br>In detail:<br>;Primary end point(s): Significant changes of <br>- relative and absolute numbers of B-cells, especially memory B-cells, Plasma blasts and Plasma cells <br>- relative and absolute numbers of T-helper, effector, central memory T-cells and regulatory T cells <br>- 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