A Phase 2, Pilot Study to Assess the Safety and Efficacy of Fostamatinib in the Treatment of Chronic Active Antibody Mediated Rejection in Renal Transplantation
The commonest cause of renal transplant failure worldwide is rejection, a process whereby the recipient's immune system recognises the transplant kidney as foreign and attacks it. One common form of rejection is due to the recipient developing antibodies against their kidney transplant. Spleen tyrosine kinase is a molecule present in immune cells which is important in the process of antibody mediated damage. Fostamatinib is a drug which inhibits spleen tyrosine kinase. This clinical trial will recruit 10 patients who have a renal transplant and a diagnosis of antibody mediated rejection. Patients will be given Fostamatinib for 12 months and will undergo a renal biopsy at 6 months and at a 12 months in order to determine whether the histological signs of antibody mediated rejection have either improved or not progressed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
All patients will be given treatment with Fostamatinib. The initial treatment dose will be 100mg of Fostamatinib twice daily for 8 weeks. If after 8 weeks the participant has not experienced any side effects and are tolerant of this dose, then the dose will increase to 150mg twice daily. This dose will continue for the duration of the study.
Imperial College NHS Healthcare Trust
London, United Kingdom
Histological changes of antibody mediated rejection assessed by a histopathologist
Pre treatment and Post treatment renal transplant biopsies will be scored by a histopathologist
Time frame: 6 months
Concentration of Protein in urine
The Level of proteinuria will be assessed by collected a urine samples which will be sent to the clinical laboratory and the protein/creatinine ratio will be calculated. The normal value of the protein/creatinine ratio should be \<10, anything higher than this indicated that the kidney is "leaky" and functioning abnormally. Levels of proteinuria will be compared pre and post treatment
Time frame: 6 months and 12 months
eGFR ( Estimated Glomerular Filtration Rate) assessed by a blood test
GFR is Glomerular Filtration Rate and it is a key indicator of renal function. The normal eGFR is 60 or more. If your eGFR is less than 60 for three months or more, your kidneys may not be working well. Th eGFR of participants will be compared pre and post treatment.
Time frame: 6 months and 12 months
Donor specific antibody levels
The mean fluorescence intensity (MFI) of donor specific antibody present will be compared pre and post treatment. Each participant will have their Donor specific antibodies measured at baseline pre treatment, this specific antibody or antibodies will be re-measured post treatment and the level (MFI) of the antibody/antibodies will be compared to pre treatment levels.
Time frame: 6 months and 12 months
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