Clinical trial NCT03221842: Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection (AMR) in Adult Renal Transplant Recipients
Official title: A Double-blind, Randomized-withdrawal, Placebo-controlled Study to Evaluate the Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection in Adult Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Antibody-mediated Rejection
Keywords: Antibody-mediated kidney transplant rejection
Renal
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2017-07-19
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized-withdrawal
Primary purpose: TREATMENT

Brief summary: This is a double-blind, randomized-withdrawal, placebo-controlled study in kidney transplant patients with AMR to evaluate the efficacy and safety of human plasma-derived C1-esterase inhibitor as add-on to standard of care (IVIG).


Eligibility criteria: Inclusion Criteria:

* Male or female at least 18 years of age;
* Evidence of at least one donor-specific antibody (DSA);
* Recipient of a kidney transplant;
* Achieved a steady-state, post-transplant eGFR ≥ 40 mL/min/1.73 m2 within 60 days of post-transplant OR a 50% increase in urine output with a 50% decrease in serum creatinine over the first 7 days post-transplant in subjects with slow or delayed graft function;
* Acute AMR.

Exclusion Criteria:

* Recipient of an en bloc kidney transplant;
* Current active hepatitis C virus (HCV) infection;
* Active bacterial or fungal infection;
* Ongoing dialysis \>2 weeks;
* Known congenital bleeding or coagulopathy disorder;
* Current cancer or a history of cancer;
* Female subjects who are pregnant or breast feeding;
* Male or female subjects who are unwilling to use contraception or who are not surgically sterile.

Primary outcomes:
measure: Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)
timeFrame: Up to 38 weeks
Secondary outcomes:
measure: Number of Participants With All-cause Allograft Failure During TP2
timeFrame: Up to 38 weeks
measure: Percent of Participants With All-cause Allograft Failure During TP2
timeFrame: Up to 38 weeks
measure: Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)
timeFrame: Baseline and 13 weeks
measure: Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2
timeFrame: Baseline and 38 weeks
measure: The Rate of Change of eGFR During TP2 as Defined by the Slope of the Mean Regression of eGFR Over Time at End of TP2
timeFrame: Up to 38 weeks
measure: Time to All-cause Allograft Failure Through the Follow up Period
timeFrame: Up to approximately 208 weeks
measure: Number of Responders at the End-of-TP1
timeFrame: Up to 13 weeks
measure: Percent of Responders at the End-of-TP1
timeFrame: Up to 13 weeks
measure: Proportion of Subjects Surviving Through the Follow-up Period
timeFrame: Up to approximately 208 weeks
measure: Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product
timeFrame: Up to approximately 42 weeks after the time of first investigational product administration
measure: Mean Pre-dose C1-esterase Inhibitor Functional Activity
timeFrame: Up to 13 weeks
measure: Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity
timeFrame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
measure: Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity
timeFrame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital (at Birmingham)
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: San Francisco
country: United States
facility: California Pacific
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Chicago
country: United States
facility: University of Illinois Chicago
state: Illinois
city: Boston
country: United States
facility: Brigham & Women's
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic (Rochester)
state: Minnesota
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg
city: Bordeaux
country: France
facility: CHU de Bordeaux. Hôpital Pellegrin
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Michalon
city: Lille
country: France
facility: Centre Regional Hospitalier Universitaire de Lille
city: Lyon
country: France
facility: Hospital Edouard Herriot Lyon
city: Paris
country: France
facility: Hopital saint Louis Paris
city: Paris
country: France
facility: Necker Hospital
city: Toulouse
country: France
facility: CHU Rangueil
city: Berlin
country: Germany
facility: Charite Berline
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
affiliation: CSL Behring
name: Program Director
role: STUDY_DIRECTOR
References:
citation: Viklicky O, Slatinska J, Novotny M, Hruba P. Developments in immunosuppression. Curr Opin Organ Transplant. 2021 Feb 1;26(1):91-96. doi: 10.1097/MOT.0000000000000844.