Antibody-mediated rejection of a kidney transplant
Conditions
Interventions
Product Name: Clazakizumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CLAZAKIZUMAB
CAS Number: 1236278-28-6
Current Sponsor code: CLAZAKIZUMAB
Other descriptive name: CLAZAKIZUMA
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Voluntary written informed consent - Age >18 years - functioning living or deceased donor allograft >365 days post-transplantation - eGFR>30ml/min/1.73m2 - Detection of HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA) - Acute/active or chronic/active ABMR (±C4d in PTC) according to BANFF 2013/2015 - Molecular ABMR score (ABMRpm) =0.2 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - active participation in another clinical trial - age 25%) - nephrotic range proteinuria >3500mg/g protein/creatinine ratio - Active vrial, bacterial or fungal infection precluding intensified immunosuppression - Active malignant disease precluding intensified immunosuppression - Abnormal liver function tests (ALT, AST, bilirubin >1.5x upper limit of normal) - Other significant liver disease - latent or active tuberculosis (positive QuantiFERON- TB GOD test, Chest X-Ray) - Administration of a live vaccine within 6 weeks of screening - neutropenia (<1 G/L) or thrombocytopenia (<100 G/L) - history of gastrointestinal perforation, diverticulitis, or inflammatory bowel disease - history of alcohol or illicit substance abuse - serious medical or psychiatric illness likely to interfere with participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): - Safety and Tolerability of Clazakizumab;Timepoint(s) of evaluation of this end point: Part A: Weeks 12 Part B: Week 52;Secondary Objective: - To investigate the pharmacokinetics and pharmacodynamics of clazakizumab - To investigate the effects of IL-6 blockade on Antibody-mediated rejection (ABMR) biomarkers: Donor specific antigen mean fluorescence intensity, serum markers of inflammation and endothelial injury - To investigate the effects of IL-6 blockade on biopsy results, microcirculation, inflammation, chronic injury and gene expression - To investigate the effects of IL-6 blockade on kidney function parameters (eGFR, urinary protein, cytokine measurements) - To investigate the effects of IL-6 blockade on cytochrome dependent drug metabolism - To investigate the effects of IL-6 blockade on leukocyte subpopulations - To investigate the effects of IL-6 blockade on Torque Teno Viremia;Main Objective: To investigate safety and tolerability of Interleukin-6 blockade by clazakizumab in kidney transplant recipients on baseline immunosuppresion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PK of clazakizumab (every visit; measurement of anti-Claza antibodies included) and of pantoprazole (0, 12, 52 weeks) - PD of clazakizumab (CRP suppression) (every visit) - Cytokines patterns and endothelial activation/injury markers in serum (0, 12, 52 weeks) - Effect on leukocyte subsets in peripheral blood - Effect on IL-6 and IL-6R gene expression in peripheral blood cells - HLA antibody levels (0, 12, 52 weeks) Maximum and sum of mean fluorescence intensity (MFI) of DSA Number of DSA Broadness of sensitization (virtual PRA) - Total Ig classes (IgG, IgA, IgM) and IgG subclasses (IgG1, 2, 3, 4) - Protocol biopsy results at 11 and 51 weeks ABMR category Microcirculation inflammation (g+ptc score) Transplant glomerulopathy (cg) and interstitial fibrosis/tubular atrophy (IFTA) scores Molecular ABMR score (molecular microscope, MMDx) Archetype analysis of gene expression profiles (molecular microscope, MMDx) - eGFR (every visit) - Protein excretion (protein/creatinine ratio) (every visit) - 1-year graft and patient survival - Occurrence of biopsy-proven acute rejection necessitating rejection treatment (52 weeks) ;Timepoint(s) of evaluation of this end point: Week 0, 12 and 52 (as applicable for each study part) | — |
Countries
Austria, Germany
Contacts
Public ContactOffice-Dept. Clinical Pharmacology
Medical University of Vienna
Outcome results
None listed