A Randomized Double-Blind Placebo-Controlled Pilot Study to Evaluate the Safety and Effect of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-Mediated Rejection in Recipients of Donor-Sensitized Kidney Transplants
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Shire
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Histopathology Endpoints
Overview
Brief Summary
The purpose of this research study is to evaluate the safety, effect, and pharmacology of C1 Esterase Inhibitor (human) in kidney transplant patients with acute Antibody-Mediated Rejection (AMR).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Change From Baseline in Histopathology Endpoints
Time Frame: Within 72 hours prior to first dose of study drug, Day 20
The protocol-specified Day 20 (post-treatment) biopsy was compared to the qualifying biopsy to assess changes in histopathology for light and immunofluorescence microscopy. The Central Pathologist provided the following categorical information from the qualifying biopsy in an AMR Scorecard: C4d Score (0-100), Margination Score (0-100) Glomerulitis Score (0-100), Vasculitis Score (0-100), Glomerulosclerosis Score (0-100), Chronic Glomerulopathy Score (0-100), Interstitial Fibrosis Score (0-100), and the Chronic Vasculitis Score (0-100), with 0 being absence of abnormal histopathology. The "qualifying" renal allograft biopsy was performed as standard of care (SOC) within 12 months after transplant and prior to screening for this study. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. A negative change from baseline indicates that histopathology has improved. Endpoint includes subjects with both Qualifying and Day 20 Biopsies.
Secondary Outcomes
- Number of Participants Who Required Salvage Splenectomy(From Day 1 to Day 90)
- Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR)(90 days after start of treatment)
- Change From Baseline in Serum Creatinine(From Day 1 to Days 20 and 90)
- Change From Baseline in Creatinine Clearance(From Day 1 to Days 20 and 90)
- Number of Plasmapheresis Sessions(From Day 1 through Days 20 and 90)
- Number of Participants With Allograft Failure(From the day of enrollment to Day 90)
- Serum Concentrations of C1 Inhibitor (C1 INH) Antigen(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Number of Deaths(From Day 1 to Day 90)
- Serum Concentrations of C1 INH Functional Activity(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Area Under The Concentration-Time Curve (AUC) of C1 INH Antigen(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Time to Maximum Plasma Concentration (Tmax) of C1 INH(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)
- Area Under The Concentration-Time Curve (AUC) of C1 INH Functional Activity(Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion)