A Pilot Study to Evaluate the Use of C1 Esterase Inhibitor (Human) in Patients With Acute Antibody-Mediated Rejection
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
2 other identifiers
interventional
18
2 countries
5
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Aug 2011
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2010
CompletedFirst Posted
Study publicly available on registry
June 22, 2010
CompletedStudy Start
First participant enrolled
August 24, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 19, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 28, 2013
CompletedResults Posted
Study results publicly available
July 9, 2015
CompletedJune 11, 2021
June 1, 2021
1.7 years
June 16, 2010
June 16, 2015
June 2, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Histopathology Endpoints
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.
Within 72 hours prior to first dose of study drug, Day 20
Secondary Outcomes (12)
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 Who Required Salvage Splenectomy
From Day 1 to Day 90
- +7 more secondary outcomes
Study Arms (2)
C1 Esterase Inhibitor (Human)
EXPERIMENTALSubjects were to receive C1 esterase inhibitor intravenously at a rate of approximately 1 mL per minute as tolerated. Subjects were to receive a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13
Normal Saline
PLACEBO COMPARATORplacebo infused as above
Interventions
Eligibility Criteria
You may qualify if:
- ≥18 years of age.
- Weigh ≥50 kg.
- Donor specific antibody identified.
You may not qualify if:
- Any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
- History of allergic reaction to C1 Esterase Inhibitor or other blood products.
- Participation in the active dosing phase of any other investigational drug study within 30 days prior to dosing with study drug.
- Pregnancy or lactation.
- Receipt of any experimental agents for AMR within 1 month prior to the first dose of study drug.
- Any infection that causes hemodynamic compromise.
- History of bleeding or clotting abnormality.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Shirelead
Study Sites (5)
ViroPharma Investigative Site
Los Angeles, California, United States
ViroPharma Investigative Site
Baltimore, Maryland, United States
ViroPharma Investigative Site
Minneapolis, Minnesota, United States
ViroPharma Investigative Site
Cincinnati, Ohio, United States
ViroPharma Investigative Site
Heidelberg, Germany
Related Publications (1)
Montgomery RA, Orandi BJ, Racusen L, Jackson AM, Garonzik-Wang JM, Shah T, Woodle ES, Sommerer C, Fitts D, Rockich K, Zhang P, Uknis ME. Plasma-Derived C1 Esterase Inhibitor for Acute Antibody-Mediated Rejection Following Kidney Transplantation: Results of a Randomized Double-Blind Placebo-Controlled Pilot Study. Am J Transplant. 2016 Dec;16(12):3468-3478. doi: 10.1111/ajt.13871. Epub 2016 Jun 27.
PMID: 27184779DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Shire
Study Officials
- STUDY DIRECTOR
Study Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2010
First Posted
June 22, 2010
Study Start
August 24, 2011
Primary Completion
April 19, 2013
Study Completion
June 28, 2013
Last Updated
June 11, 2021
Results First Posted
July 9, 2015
Record last verified: 2021-06