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

Phase 3TerminatedNCT03221842

CSL Behring63 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Antibody-mediated Rejection

Interventions

C1-esterase inhibitorDRUG

C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution

PlaceboDRUG

Excipients of C1-INH plus albumin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (26)

University of Alabama Hospital (at Birmingham)

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 38 weeks

Secondary Outcomes

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

Time frame: Up to 38 weeks

Percent of Participants With All-cause Allograft Failure During TP2

Time frame: Up to 38 weeks

Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)

Time frame: Baseline and 13 weeks

Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2

Time frame: Baseline and 38 weeks

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.

Time frame: Up to 38 weeks

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.

Data from ClinicalTrials.gov

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Mayo Clinic Arizona

Phoenix, Arizona, United States

California Pacific

San Francisco, California, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

University of Illinois Chicago

Chicago, Illinois, United States

Brigham & Women's

Boston, Massachusetts, United States

Mayo Clinic (Rochester)

Rochester, Minnesota, United States

St. Barnabas Medical Center

Livingston, New Jersey, United States

NYU

New York, New York, United States

Columbia University

New York, New York, United States

...and 16 more locations

Time frame: Up to approximately 208 weeks

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.

Time frame: Up to 13 weeks

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.

Time frame: Up to 13 weeks

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.

Time frame: Up to approximately 208 weeks

Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product

Time frame: Up to approximately 42 weeks after the time of first investigational product administration

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.

Time frame: Up to 13 weeks

Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity

Time frame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1

Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity

Time frame: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1