Prophylaxis of rejection in kidney allograft recipients (by immunosuppression) MedDRA version: 12.1 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection
Conditions
Sponsors
Astellas Pharma Europe Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years. 2. End stage kidney disease and a suitable candidate for primary renal transplantation or retransplantation (unless the graft was lost from rejection within 6 months). 3. Receiving a kidney transplant from a deceased or living (non HLA identical) donor with compatible AB0 blood type. 4. Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ICH/286/95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner. 5. Capable of understanding the purpose and risks of the study, fully informed and having given written informed consent (signed Informed Consent has been obtained). 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Receiving or having previously received an organ transplant other than a kidney. 2. Cold ischemia time of the donor kidney > 30 hours. 3. Panel Reactive Antibody (PRA) >20%. 4. Previous renal transplant lost within one year for immunological reasons. 5. Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest). 6. Significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels = 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor. 7. Diagnosis of Diabetes Mellitus prior to transplantation (treated with prescribed medications or diet controlled) or where there is evidence of a previous positive OGTT in the patients medical history or previous diagnosis of gestational diabetes or Baseline HbA1C =6.5mmol/L. 8. Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s). 9. Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (e.g. for Lupus Disease, FSGN etc) other than minimal levels of immunosuppressant following failure of a previous transplantation without nephrectomy. 10. Where Physician considers long term steroid treatment is necessary for the prevention of recurrent auto immune mediated renal disease or if the subject requires ongoing dosing with corticosteroids during the study for any other condition. 11. Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer. 12. Pregnant woman or breast-feeding mother. 13. Subject or donor known to be HIV positive. 14. Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, Basiliximab, mycophenolate mofetil or any of the product excipients. 15. Evidence of malignant disease within the last 5 years other than Basal Cell Carcinoma or Squamous Cell Carcinoma. 16. Currently participating in another clinical trial and/or has taken an investigational drug within 28 days prior to randomization. 17. Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator. 18. Unlikely to comply with the visits scheduled in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the two treatment arms with regard to incidence of new onset diabetes Mellitus as per the American Diabetic Association criteria at any point up to 24 weeks after kidney transplantation. Arm 1: Advagraf + Basiliximab + MMF + Steroids (discontinued at 10 days) Arm 2: Advagraf + Basiliximab + MMF + Steroids (optional intra-op Bolus only);Secondary Objective: to compare the safety and efficacy profiles of the two therapy regimens with each other;Primary end point(s): The primary endpoint of the study is the incidence of New Onset Diabetes Mellitus defined as: Occurrence of NODAT as per ADA criteria at any point up to 24 weeks after kidney transplantation: 1. HbA1C =6.5% at or after the week 12 visit. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. OR 2. FPG =126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours prior to blood sampling.* OR 3. 2-h plasma glucose =200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR 4. Symptoms of hyperglycemia and a casual plasma glucose =200 mg/dl (11.1mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, and unexplained weight loss. * In the absence of unequivocal hyperglycemia, criteria 2) & 3) should be confirmed by repeat testing (using the same test) =30 days after the initial positive assessment. A repeat test is not required for 1) and 4). A single HbA1C result of = 6.5% at or after week 12 or unequivocal hyperglycemia (4) is sufficient to confirm diagnosis of NODAT. For 2) & 3) the diagnosis will be classed as the time of the first test showing above criteria only if confirmed by a second reading using the same test, or if treatment | — |
Countries
Belgium, Czech Republic, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Portugal, Romania, Slovakia, Spain, Sweden
Outcome results
None listed