Renal Transplant Rejection
Conditions
Keywords
Renal transplant rejection, donor specific antibody, antibody mediated rejection, spleen tyrosine kinase, fostamatinib
Brief summary
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
Detailed description
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.
Interventions
DRUGFostamatinib
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.
Sponsors
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Intervention model description
Single centre, not randomised, open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to any study specific screening procedures. * Male or female, at least 18 years of age * Females must be either post-menopausal, surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or, if of child-bearing potential, must not be pregnant or lactating. * Patients must be established on tacrolimus maintenance immunosuppression * A pre-study renal biopsy obtained within 3 months prior to Baseline (Visit 1) will be reviewed by a renal pathologist to ensure subjects meet the following Banff histologic entry criteria: If C4d positive: Microcirculation inflammation score (g+ptc) ≥1 If C4d negative: Microcirculation inflammation score (g+ptc) ≥2 Chronic glomerulopathy (cg) score ≥1b or significant Peritubular Capillary Basement Membrane Multilayering (PTCBML) Chronic tubulo-interstitial scarring ≤50% Glomerular global obsolescence ≤50% Sample must contain at least 7 glomeruli and 1 artery * Otherwise in stable health as determined by the Investigator based on medical history and laboratory tests during the screening period. See
Exclusion criteria
for specific exclusions. * In the Investigator's opinion, understand the duration of the study (up to 52 weeks), including the requirements for renal biopsies, and has the ability to understand the nature of the study and any hazards of participation and to communicate satisfactorily with the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histological changes of antibody mediated rejection assessed by a histopathologist | 6 months | Pre treatment and Post treatment renal transplant biopsies will be scored by a histopathologist |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Protein in urine | 6 months and 12 months | 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 |
| eGFR ( Estimated Glomerular Filtration Rate) assessed by a blood test | 6 months and 12 months | 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. |
| Donor specific antibody levels | 6 months and 12 months | 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. |
Countries
United Kingdom
Outcome results
None listed