A Multicenter Study to Evaluate the Efficacy and Safety of Cinryze® for the Treatment of Acute Antibody-mediated Rejection in Participants With Kidney Transplant
Condition: Acute Antibody-Mediated Rejection (AMR)
Intervention: Cinryze®; Placebo
Intervention description: Participants will receive 5000 Units of CINRYZE (50 millilitre [mL] of CINRYZE/ 50 mL of normal saline) on Day 1 and 2500 Units of CINRYZE (25 mL of CINRYZE/ 75 mL of normal saline) on Day 3, 5, 7, 9, 11, and 13 respectively.; Participants will receive 7 doses of matched placebo over 13 days of treatment.
Intervention MeSH terms: Complement C1 Inhibitor Protein
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The main purpose of the study is to evaluate the efficacy of CINRYZE administered with
      plasmapheresis, plasma exchange, or immune adsorption treatments and sucrose-free
      immunoglobulin (IVIg) for the treatment of acute antibody-mediated rejection (AMR) of renal
      allograft in kidney transplant recipients as measured by the proportion of participants with
      new or worsening transplant glomerulopathy (TG) at 6 months after treatment initiation.
    

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®).