Clinical trial NCT01147302: A Pilot Study to Evaluate the Use of C1 Esterase Inhibitor (Human) in Patients With Acute Antibody-Mediated Rejection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft Rejection
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria include:

* ≥18 years of age.
* Weigh ≥50 kg.
* Donor specific antibody identified.

Exclusion Criteria include:

* 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.

Primary outcomes:
measure: Change From Baseline in Histopathology Endpoints
timeFrame: Within 72 hours prior to first dose of study drug, Day 20
Secondary outcomes:
measure: Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR)
timeFrame: 90 days after start of treatment
measure: Change From Baseline in Serum Creatinine
timeFrame: From Day 1 to Days 20 and 90
measure: Change From Baseline in Creatinine Clearance
timeFrame: From Day 1 to Days 20 and 90
measure: Number of Plasmapheresis Sessions
timeFrame: From Day 1 through Days 20 and 90
measure: Number of Participants Who Required Salvage Splenectomy
timeFrame: From Day 1 to Day 90
measure: Number of Deaths
timeFrame: From Day 1 to Day 90
measure: Number of Participants With Allograft Failure
timeFrame: From the day of enrollment to Day 90
measure: Serum Concentrations of C1 Inhibitor (C1 INH) Antigen
timeFrame: 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
measure: Serum Concentrations of C1 INH Functional Activity
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of C1 INH
timeFrame: 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
measure: Area Under The Concentration-Time Curve (AUC) of C1 INH Antigen
timeFrame: 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
measure: Area Under The Concentration-Time Curve (AUC) of C1 INH Functional Activity
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: ViroPharma Investigative Site
state: California
city: Baltimore
country: United States
facility: ViroPharma Investigative Site
state: Maryland
city: Minneapolis
country: United States
facility: ViroPharma Investigative Site
state: Minnesota
city: Cincinnati
country: United States
facility: ViroPharma Investigative Site
state: Ohio
city: Heidelberg
country: Germany
facility: ViroPharma Investigative Site
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.