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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT02547220
First received: September 2, 2015
Last updated: February 15, 2017
Last verified: February 2017

September 2, 2015
February 15, 2017
October 2015
February 2022   (Final data collection date for primary outcome measure)
Evaluate efficacy for the treatment of acute AMR of renal allograft in kidney transplant recipients as measured by the proportion of subjects with new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation using Banff criteria [ Time Frame: Screening to Month 6 ]
Administer CINRYZE with plasmapheresis, plasma exchange, or immune absorption treatments and sucrose-free immunoglobulin (IVIg).
Proportion of subjects with new or worsening transplant glomerulopathy (TG) within 6 months post-treatment as determined by Banff criteria [ Time Frame: Screening to Month 6 ]
Complete list of historical versions of study NCT02547220 on ClinicalTrials.gov Archive Site
  • Proportion of subjects with all-cause graft failure [ Time Frame: Screening to Month 48 (End of Study [EOS]) (+/- 14 days) ]
  • Time to all-cause graft failure [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Proportion of subjects with graft failure due to AMR [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Change in renal allograft function (eGFR) as calculated by the Modification of Diet in Renal Disease (MDRD formula) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Change from baseline in histopathology at Month 6 post-treatment per Banff criteria [ Time Frame: Screening to Month 6 ]
  • Time to first recurrence of biopsy-proven acute AMR after dosing [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Change from baseline in serum Cr [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Overall subject survival [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Treatment-emergent adverse events (TEAEs) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Change in Vital Signs (Heart Rate) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Change in Vital Signs (Blood Pressure) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • antibodies to C1inhibitor (INH) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • clinical safety laboratory testing (Hematology) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • clinical safety laboratory testing (Serum Chemistry) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • clinical safety laboratory testing (Serum Blood urea nitrogen/Cr) [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • time to graft failure due to AMR [ Time Frame: Screening to Month 48 (EOS) (+/- 14 days) ]
  • Proportion of subjects with all-cause graft failure) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Time to all-cause graft failure [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Proportion of subjects with graft failure due to AMR [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Change from baseline in renal allograft function (eGFR as calculated by the Modification of Diet in Renal Disease (MDRD formula) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Change from baseline in histopathology at Month 6 post-treatment per Banff criteria [ Time Frame: Screening to Month 6 ]
  • Time to first recurrence of biopsy-proven acute AMR after dosing [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Change from baseline in serum Cr [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Proportion of subjects with salvage splenectomy [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Overall subject survival [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Frequency of donor- specific antibody (DSA) reduction therapy beyond protocol-mandated treatment [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Treatment-emergent adverse events (TEAEs) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Change in Vital Signs (Heart Rate) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • Change in Vital Signs (Blood Pressure) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • antibodies to C1inhibitor (INH) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • clinical safety laboratory testing (Hematology) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • clinical safety laboratory testing (Serum Chemistry) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • clinical safety laboratory testing (Serum Blood urea nitrogen/Cr) [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
  • time to graft failure due to AMR [ Time Frame: Screening to Month 48(+/- 14 days) EOS ]
Not Provided
Not Provided
 
A Multicenter Study to Evaluate the Efficacy and Safety of Cinryze® for the Treatment of Acute Antibody-mediated Rejection in Patients With Kidney Transplant
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
To evaluate the efficacy of Cinryze® given for the treatment of acute antibody-mediated rejection (of renal allograft) (AMR) in kidney transplant recipients as measured by the proportion of subjects with new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Acute Antibody-Mediated Rejection (AMR)
  • Biological: Cinryze®
    7 doses of study drug over 13 days
  • Drug: Placebo
    7 doses of placebo over 13 days
  • Experimental: Cinryze®
    eligible subjects with biopsy-proven AMR will be randomized (56 per arm) to receive either IV Cinryze® or placebo
    Intervention: Biological: Cinryze®
  • Placebo Comparator: Placebo
    eligible subjects with biopsy-proven AMR will be randomized (56 per arm) to receive either IV Cinryze® or placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
112
February 2022
February 2022   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Be >=18 and <=70 years of age.
  2. Weigh >=45 kg with a body mass index (BMI) <35 kg/m^2 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 PTC and/or glomeruli with or without evidence of C4d deposition by immunohistopathology according to 2013 Banff criteria.
  5. Have achieved adequate renal function defined as: Pre-AMR baseline eGFRMDRD >=20 mL/min/1.72m^2 for a qualifying AMR episode occurring <=21 days after transplant or pre-AMR baseline eGFRMDRD >=30 mL/min/1.72m^2 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 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 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.
  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 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 HCV infection.
  7. Have had a recent myocardial infarction (MI) or transient ischemic attack (TIA) within the past 6 months.
  8. Have a history of abnormal bleeding, clotting, or any coagulopathy (excluding a history of clotted hemodialysis access or superficial thrombophlebitis in the absence of medically confirmed coagulopathy).
  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 prior to dosing with investigational product:

    • Within 24 hours prior to subject dosing, white blood cell (WBC) count <0.5×10^9/L or >20×10^9/L (the value of >20×10^9/L should be excluded if obtained during steroid treatment)
    • Within 72 hours prior to subject 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®)
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Senior)
No
Contact: Shire Contact clinicaltransparency@shire.com
United States,   Canada,   France,   Germany,   Netherlands,   Spain
 
 
NCT02547220
SHP616-302
Yes
Not Provided
Not Provided
Not Provided
Shire
Shire
Not Provided
Principal Investigator: Shire Study Physician Shire
Shire
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP