Acute cellular rejection after kidney transplantation MedDRA version: 16.1 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Ilaris
Pharmaceutical Form: Injection
Sponsors
Medizinische Hochschule Hannover
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Male or female patients aged at least 18 years at the time of study inclusion 2 Kidney transplant within the last 14 months 3 Evidence of acute cellular tubulointerstitial rejection in kidney transplant according to Banff criteria (grade IA or IB ), which has been detected in a protocol or indication biopsy, without evidence of more than 20 CD20-positive B cells per high power field in the infiltrate and without evidence glomerulitis or capillaritis 4 C4d and SV40 negativity in the biopsy 5 eGFR = 30 ml/min/1,73 m2 calculated by MDRD formula before diagnosis of rejection 6 In female patients of childbearing potential existence of a negative pregnancy test and consent to a highly effective method of contraception (Pearl Index =65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1 Known contraindications or intolerance of canakinumab or concomitant medication 2 Administration of canakinumab within 14 months of study entry 3 Administration of another biologicals (eg, rituximab or basiliximab) or of a TNF-alpha blocker within the last 4 weeks prior to study entry 4 Simultaneous participation in another clinical trial 5 Body weight < 40 kg 6 Pregnant or lactating women 7 People who are not in a position to understand nature, significance and implications of the clinical study and to identify and align their will hereafter (pursuant to § 40 para 4 and § 41 para 2 and para 3 AMG) 8 Presence of CMV infection, HIV infection, replicative hepatitis B or hepatitis C, other serious infections, or a high risk for TB 9 Patients with previously known neutropenia (< 1.5/nl) 10 Heart failure NYHA stage III-IV 11 High-grade arrhythmias (eg ventricular tachycardia, symptomatic bradycardia , other hemodynamically significant arrhythmias ) 12 Unstable coronary artery disease 13 History of splenectomy 14 Contraindication regarding a re-biopsy of the allograft (eg, coagulopathy, anticoagulation) 15 Presence of malignoma 16 Seronegativity (IgG) for EBV and VZV 17 Other exclusion criteria after assessment of the treating physician (eg, deterioration of general condition, derailed metabolic situation, high risk, such as AB0-incompatible kidney transplantation)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We want to demonstrate that treatment with canakinumab in patients with histological evidence of acute T-cell-mediated rejection after kidney transplantation leads to a regression of the infiltrates in the graft biopsy.;Secondary Objective: not applicable;Primary end point(s): Regression of the infiltrate in the graft biopsy 14 days after treatment with canakinumab, i.e., rejection according to Banff criteria is no longer detectable.;Timepoint(s) of evaluation of this end point: 14 days after treatment with study drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 Delta eGFR using the change in serum creatinine between the time of diagnosis of rejection and 14 and 28 days after treatment with canakinumab, as well as in relation to the baseline eGFR, which was present before the rejection . 2 Proportion of patients with stable graft function based on serum creatinine (stage I) and with improvement of graft function after 14-28 days based on serum creatinine (stage II) . 3 Proportion of patients with persistent rejection, graft loss, severe infection or death within the follow-up period of 1 year after administration of study drug 4 Differentially expressed genes in the first biopsy with rejection diagnosis versus the second biopsy after 14 days (intraindividual comparison) as well as comparison of patients with regression of the infiltrates in the second biopsy after 14 days versus lack of regression using microarray RNA analysis 5 Serum and urine biomarkers (eg proteomics), that are associated with acute rejection, at the time of diagnosis of rejection compared to 14 days after treatment (intra-individual comparison) as well as comparison of patients with regression of the infiltrates in the second biopsy after 14 days versus lack of regression.;Timepoint(s) of evaluation of this end point: 14 and 28 days and within the 1 year follow-up period after treatment with study drug. | — |
Countries
Germany
Contacts
Public ContactInvestigator
Studienzentrum für Nieren- und Hochdruckerkrankungen
Outcome results
None listed