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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
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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