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

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

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-000348-17-GB

Enrollment

120

Registered

2017-05-12

Start date

2018-01-19

Completion date

Unknown

Last updated

2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Refractory AMR in adult renal transplant participants MedDRA version: 20.0 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders

Interventions

Trade Name: Berinert 1500 IU Powder and solvent for solution for injection Product Name: C1-INH [C1-esterase Inhibitor, Human (500 IU/mL)] Product Code: C1-INH Pharmaceutical Form: Lyophilisate and so

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1) Male or female at least 18 years of age; 2) Evidence of at least one donor-specific antibody (DSA); 3) Recipient of a kidney transplant; 4) 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 posttransplant in subjects with slow or delayed graft function; 5) Acute AMR. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 107 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13

Exclusion criteria

Exclusion criteria: 1) Recipient of an en bloc kidney transplant; 2) Current active hepatitis C virus (HCV) or hepatitis B Virus (HBV) infection; 3) Active bacterial or fungal infection; 4) Ongoing dialysis >2 weeks; 5) Known congenital bleeding or coagulopathy disorder; 6) Current cancer or a history of cancer; 7) Female subjects who are pregnant or breast feeding; 8) Male or female subjects who are unwilling to use contraception or who are not surgically sterile.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of the study is to evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients. ;Secondary Objective: The secondary objectives of the study are: 1. To evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients. 2. To evaluate the safety of C1-INH in the treatment of refractory AMR in renal allograft recipients. 3. To evaluate the pharmacokinetics of C1-INH during the treatment of refractory AMR in renal allograft recipients. ;Primary end point(s): Proportion of subjects with loss-of-response at the end-of- Treatment Period 2 (TP2);Timepoint(s) of evaluation of this end point: Up to approximately 25 weeks	—

Measure

Time frame

Main Objective: The primary objective of the study is to evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients. ;Secondary Objective: The secondary objectives of the study are: 1. To evaluate the efficacy of C1-INH in the treatment of refractory AMR in renal allograft recipients. 2. To evaluate the safety of C1-INH in the treatment of refractory AMR in renal allograft recipients. 3. To evaluate the pharmacokinetics of C1-INH during the treatment of refractory AMR in renal allograft recipients. ;Primary end point(s): Proportion of subjects with loss-of-response at the end-of- Treatment Period 2 (TP2);Timepoint(s) of evaluation of this end point: Up to approximately 25 weeks

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Secondary

Measure	Time frame
Secondary end point(s): -Proportion of subjects with all-cause allograft failure through the Follow-up Period (ie, within 48 months after enrollment) -The difference between the end-of-TP1 eGFR and baseline eGFR -The difference between the end-of-TP2 eGFR and the end-of-TP1 eGFR -The rate of change of eGFR during TP2 as defined by the slope of the mean regression of eGFR over time in TP2 -Time (days) to all-cause allograft failure through the Follow up Period (ie, within 48 months after enrollment) -Proportion of responders at the end-of-Treatment Period 1 -Proportion of subjects surviving through the Follow-up Period -Proportion of subjects with any adverse event (AE) assessed as related to investigational product -Mean pre-dose C1-esterase inhibitor functional activity -Time to maximum plasma concentration (Cmax) for C1-INH functional activity -Area under the plasma concentration time curve (AUC0-t) for C1-INH functional activity;Timepoint(s) of evaluation of this end point: - Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 25 weeks - Screening and up to approximately 38 weeks - Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 208 weeks - Up to approximately 42 weeks after the time of first investigational product administration - Day 1, Week 12, and Week 38 - Up to 72 hours after dose - Up to 72 hours after dose	—

Measure

Time frame

Secondary end point(s): -Proportion of subjects with all-cause allograft failure through the Follow-up Period (ie, within 48 months after enrollment) -The difference between the end-of-TP1 eGFR and baseline eGFR -The difference between the end-of-TP2 eGFR and the end-of-TP1 eGFR -The rate of change of eGFR during TP2 as defined by the slope of the mean regression of eGFR over time in TP2 -Time (days) to all-cause allograft failure through the Follow up Period (ie, within 48 months after enrollment) -Proportion of responders at the end-of-Treatment Period 1 -Proportion of subjects surviving through the Follow-up Period -Proportion of subjects with any adverse event (AE) assessed as related to investigational product -Mean pre-dose C1-esterase inhibitor functional activity -Time to maximum plasma concentration (Cmax) for C1-INH functional activity -Area under the plasma concentration time curve (AUC0-t) for C1-INH functional activity;Timepoint(s) of evaluation of this end point: - Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 25 weeks - Screening and up to approximately 38 weeks - Up to approximately 208 weeks - Up to approximately 13 weeks - Up to approximately 208 weeks - Up to approximately 42 weeks after the time of first investigational product administration - Day 1, Week 12, and Week 38 - Up to 72 hours after dose - Up to 72 hours after dose

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Countries

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

Contacts

Public ContactTrial Registration Coordinator

CSL Behring LLC

clinicaltrials@cslbehring.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026