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

Antibody-mediated Rejection Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03221842
• Other study ID #: CSL842_3001
• Secondary ID: 2017-000348-17
• Status: Terminated
• Phase: Phase 3
• Start date: November 6, 2017
• Est. completion date: January 20, 2021

Study information

• Verified date: July 2022
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: January 20, 2021
• Est. primary completion date: January 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Antibody-mediated Rejection

Intervention

Drug:
• C1-esterase inhibitor
C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution
• Placebo
Excipients of C1-INH plus albumin

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
France	CHU de Bordeaux. Hôpital Pellegrin	Bordeaux
France	CHU de Grenoble - Hôpital Michalon	Grenoble
France	Centre Regional Hospitalier Universitaire de Lille	Lille
France	Hospital Edouard Herriot Lyon	Lyon
France	Hopital saint Louis Paris	Paris
France	Necker Hospital	Paris
France	CHU Rangueil	Toulouse
Germany	Charite Berline	Berlin
Netherlands	Leiden University Medical Center	Leiden
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
United Kingdom	Guy's Hospital	London
United States	University of Alabama Hospital (at Birmingham)	Birmingham	Alabama
United States	Brigham & Women's	Boston	Massachusetts
United States	University of Illinois Chicago	Chicago	Illinois
United States	Houston Methodist	Houston	Texas
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	University of Wisconsin	Madison	Wisconsin
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	NYU	New York	New York
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic (Rochester)	Rochester	Minnesota
United States	California Pacific	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)	Loss of response is defined as 1 of the following, whichever occurs first: Decline in Estimated Glomerular Filtration Rate (eGFR), or; Allograft failure, or; Subject death by any cause.	Up to 38 weeks
Secondary	Number of Participants With All-cause Allograft Failure During TP2	Allograft failure is defined as 1 of the following: Allograft nephrectomy, institution of permanent dialysis, or return to the transplant waitlist for renal transplant, whichever occurs first, OR; Subject death by any cause	Up to 38 weeks
Secondary	Percent of Participants With All-cause Allograft Failure During TP2		Up to 38 weeks
Secondary	Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)		Baseline and 13 weeks
Secondary	Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2		Baseline and 38 weeks
Secondary	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	The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.	Up to 38 weeks
Secondary	Time to All-cause Allograft Failure Through the Follow up Period	The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.	Up to approximately 208 weeks
Secondary	Number of Responders at the End-of-TP1	Responders were defined as subjects whose End-of-TP1 eGFR was = 90% of baseline eGFR and = 20 mL/min/1.73 m2.	Up to 13 weeks
Secondary	Percent of Responders at the End-of-TP1	Responders were defined as subjects whose End-of-TP1 eGFR was = 90% of baseline eGFR and = 20 mL/min/1.73 m2.	Up to 13 weeks
Secondary	Proportion of Subjects Surviving Through the Follow-up Period	The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.	Up to approximately 208 weeks
Secondary	Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product		Up to approximately 42 weeks after the time of first investigational product administration
Secondary	Mean Pre-dose C1-esterase Inhibitor Functional Activity	C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity in plasma is described as a percent.	Up to 13 weeks
Secondary	Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity	C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity is described as a percent.	Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1
Secondary	Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity		Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1