A Multicenter Study to Evaluate the Efficacy and Safety of Cinryze® for the Treatment of Acute Antibody-mediated Rejection in Participants With Kidney Transplant

Launched by SHIRE · Sep 10, 2015

Keywords

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Eligibility criteria

• Inclusion Criteria:
• • 1. Be greater than or equal to (\>=) 18 and less than or equal to (\<=) 70 years of age.
• • 2. Weigh \>= 45 kg with a body mass index (BMI) less than (\<) 35 kilogram (kg)/meter (m)\^2 at screening.
• • 3. Have human leukocyte antigen (HLA) donor-specific antibody (DSA) identified at the time of diagnosis of AMR. If it is anticipated that the local DSA results will not be available within the screening period, previously obtained local DSA results can be used to assess eligibility, if obtained after kidney transplant and within 30 days prior to the qualifying AMR episode. In any instance, a local DSA test should still be performed at the time of AMR diagnosis.
• • 4. Have a first qualifying episode of AMR in the participant's current renal allograft between 72 hours (h) and 12 months after transplant defined by a renal allograft biopsy demonstrating neutrophil and/or monocyte infiltration in the peritubular capillaries (PTC) and/or glomeruli with or without evidence of 4th complement protein degradation product (C4d) deposition by immunohistopathology according to 2013 Banff criteria.
• • 5. Have achieved adequate renal function defined as: Pre-AMR baseline estimated glomerular filtration rate calculated by the Modification of Diet in Renal Disease (eGFRMDRD) \>=20 millilitre (mL)/minute (min) /1.73m\^2 for a qualifying AMR episode occurring \<=21 days after transplant or pre-AMR baseline eGFRMDRD \>=30 mL/min/1.7m\^2 for a qualifying AMR episode occurring greater than (\>) 21 days after transplant. The pre-AMR baseline is the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode. If more than 1 eGFRMDRD value is available, a mean of the 2 highest values (at least 1 day apart and both prior to the AMR episode) will be used as the pre-AMR baseline value. If no eGFRMDRD was obtained within 30 days prior to biopsy, it can be evaluated within a 60 day period.
• • 6. Receive first dose of investigational product after 7 days after the kidney transplant procedure and within 7 days after the qualifying renal allograft biopsy procedure that was positive for AMR.
• • 7. Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
• • 8. If female and of child-bearing potential, must have a negative urine pregnancy test confirmed by a negative serum beta human chorionic gonadotropin (beta-HCG) pregnancy test at the Screening Visit and must have a negative urine pregnancy test at the Day 1 visit.
• • 9. Agree to comply with any applicable contraceptive requirements of the protocol.
• Exclusion Criteria:
• • 1. Have received pediatric en bloc kidney transplant.
• • 2. Have primary Focal Segmental Glomerulosclerosis, rapidly progressive glomerulonephritis, membrano-proliferative glomerulonephritis type 1 (including C3 glomerulopathy), "dense deposit disease", or thrombotic microangiopathy as the cause of native kidney failure.
• • 3. Have prior or concurrent non-renal solid organ transplant or hematopoietic stem cell transplant (HSCT) or have more than 2 completed kidney transplant procedures (note: 1 double kidney transplant procedure is considered to be 1 procedure).
• • 4. Have a known neoplastic lesion in the transplanted allograft
• • 5. Have, any ongoing infection that causes hemodynamic compromise or as determined by the investigator, any surgical or medical condition that could interfere with the administration of investigational product, interpretation of study results, or could compromise participant safety, including (as determined by the transplanting surgeon and documented in the operative report) any major technical complications of the renal artery, renal vein, or ureteral anastomosis
• • 6. Have ongoing treatment for hepatitis C virus (HCV) infection.
• • 7. Have had a recent myocardial infarction (MI) within the past 6 months and/or at the time of screening are treated with anticoagulants and/or antiplatelet agents (excluding aspirin) for a previous myocardial infarction.
• • 8. Have a history of: abnormal bleeding, clotting events or disorders (excluding a history of clotted hemodialysis access or superficial thrombophlebitis in the absence of medically confirmed coagulopathy), any coagulopathy (documented or clinically suspected) For example, participants should be excluded if they have a history of renal allograft arterial or venous thrombosis, deep vein thrombosis, pulmonary embolism, ischemic cerebrovascular accident (stroke) or transient ischemic attack (TIA), any large vessel thrombosis.
• • 9. Have a history of allergic reaction to CINRYZE or other blood products.
• • 10. Have had any change in androgen therapy (example, danazol, oxandrolone, stanozolol, testosterone), tranexamic acid, epsilon-aminocaproic acid, or other fibrinolytics within 3 months before the first dose of investigational product.
• • 11. Have participated in the active dosing phase of any other investigational drug study within 30 days prior to dosing with investigational product.
• • 12. Have any of the following local laboratory values reported prior to dosing with investigational product: Within 24 h prior to participant dosing, white blood cell (WBC) count \<0.5×109/litre (L) or \>20×109/L (the value of \>20×109/L should be excluded if obtained during steroid treatment), Within 24 h prior to participant dosing platelet count \<25×109/L or \>600×109/L
• • 13. Be pregnant or breastfeeding.
• • 14. Have received any of the following agents within 1 month prior to the first dose of investigational product: Sucrose-containing intravenous immunoglobulin (IVIg), Any C1 inhibitor (C1 INH) (plasma-derived \[example, CINRYZE®, Berinert®, Cetor®\] or recombinant \[example, Rhucin®\]), Eculizumab (Soliris®), Ecallantide (Kalbitor®).