A randomized double-blind placebo-controlled study to evaluate the efficacy and safety of Cinryze® (C1 esterase inhibitor [human]) for the treatment of acute antibody-mediated rejection in kidney transplant patients
- Conditions
- kidney transplant10038430
- Registration Number
- NL-OMON44758
- Lead Sponsor
- Shire
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 7
1.Be >= 18 and <=70 years of age.
2.Weigh >=45 kg with a body mass index (BMI) <35 kg/m2 at screening.
3.Have HLA 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 subject's current renal allograft between 72 hours and 12 months after transplant defined by a renal allograft biopsy demonstrating neutrophil and/or monocyte infiltration in the peritubular capillaries and/or glomeruli with or without evidence of C4d by immunohistopathology according to 2013 Banff criteria for AMR.
5.Have achieved adequate renal function defined as: Pre-AMR baseline eGFRMDRD >=20 mL/min/1.73m2 for a qualifying AMR episode occurring <=21 days after transplant or pre-AMR baseline eGFRMDRD >=30 mL/min/1.73m2 for a qualifying AMR episode occurring >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 one 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 at least 7 days after kidney transplant 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, have a negative urine pregnancy test confirmed by a negative serum beta human chorionic gonadotropin 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.
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 and/or medical monitor, any surgical or medical condition that could interfere with the administration of investigational product, interpretation of study results, or could compromise patient 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 hepatitits C virus (HCV) infection.
7.Have had a myocardial infarction (MI) within the past 6 months and/or at the time of screening are treated with anticoagulants and/or antiplatelet agents (excluding asprin) 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 (docuemented or clinically suspected). For example, patients should be excluded if they have a history of renal allograft arterial or venous thrombosis, deep vein thrombosis, pulmonary embolism, ischemic cerebrovasculara accident (stroke) or transient ischemic attack (TIA), any large vessel thrmobosis..
9.Have a history of allergic reaction to CINRYZE or other blood products.
10.Have had any change in androgen therapy (eg, 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 hours prior to subject dosing, white blood cell count <0.5×10^9/L or >20×10^9/L (the value of >20 x 10^9/L should be excluded if obtained during steroid treatment)
Within 24 hours prior to dosing , platelet count <25×10^9/L or >600×10^9/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 IVIg
Any C1 INH (plasma-derived [eg, CINRYZE®, Berinert®, Cetor®] or recombinant [eg, Rhucin®])
Eculizumab (Soliris®)
Ecallantide (Kalbitor®)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint: Proportion of subjects with new or worsening TG at 6<br /><br>months after treatment initiation as determined by Banff criteria</p><br>
- Secondary Outcome Measures
Name Time Method <p>Key Secondary Efficacy Endpoint: Proportion of subjects with all-cause graft<br /><br>failure (ie, return to<br /><br>permanent dialysis and/or removal of the transplanted kidney and/or clinical<br /><br>determination of cessation of<br /><br>graft function in any subject that had received a pre-emptive kidney transplant<br /><br>prior to starting dialysis) at 4 years following treatment of the initial<br /><br>qualifying AMR episode<br /><br><br /><br>Secondary objectives from study entry to 6 months:<br /><br>- To assess renal function<br /><br>- To assess proteinuria<br /><br>- To assess change in histopathology<br /><br>- To assess graft outcomes<br /><br>Secondary objectives from study entry to 4 years:<br /><br>- To assess renal function<br /><br>- To assess proteinuria<br /><br>- To assess graft outcomes<br /><br>- To assess resolution of AMR<br /><br>- To assess safety and tolerability of CINRYZE in kidney transplant<br /><br>- To assess subject survival status</p><br>