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

July 25, 2022 updated by: CSL Behring

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

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
63

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • Universitair Ziekenhuis Gasthuisberg
  • France
      • Bordeaux, France, 33000
        • CHU de Bordeaux. Hôpital Pellegrin
      • Grenoble, France, 38043
        • CHU de Grenoble - Hôpital Michalon
      • Lille, France, 59000
        • Centre Regional Hospitalier Universitaire de Lille
      • Lyon, France, 69003
        • Hospital Edouard Herriot Lyon
      • Paris, France, 75743
        • Necker Hospital
      • Paris, France, 75010
        • Hôpital Saint Louis Paris
      • Toulouse, France, 31059
        • CHU Rangueil
  • Germany
      • Berlin, Germany, 10117
        • Charite Berline
  • Netherlands
      • Leiden, Netherlands, 2300
        • Leiden University Medical Center
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
  • United Kingdom
      • London, United Kingdom, SE19RT
        • Guy'S Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama Hospital (at Birmingham)
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Arizona
    • California
      • San Francisco, California, United States, 94115
        • California Pacific
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale New Haven Hospital
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Women's
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic (Rochester)
    • New Jersey
      • Livingston, New Jersey, United States, 07039
        • St. Barnabas Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10016
        • NYU
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist
    • Wisconsin
      • Madison, Wisconsin, United States, 53705-2281
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: C1-INH
C1-esterase inhibitor
Drug: C1-esterase inhibitor
C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution
Other Names:
  • C1-INH
PLACEBO_COMPARATOR: Placebo
Excipients of C1-INH plus albumin
Drug: Placebo
Excipients of C1-INH plus albumin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)
Time Frame: Up to 38 weeks

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With All-cause Allograft Failure During TP2
Time Frame: Up to 38 weeks

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
Percent of Participants With All-cause Allograft Failure During TP2
Time Frame: Up to 38 weeks
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
Baseline and 13 weeks
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2
Time Frame: Baseline and 38 weeks
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
Time Frame: Up to 38 weeks
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
Time to All-cause Allograft Failure Through the Follow up Period
Time Frame: Up to approximately 208 weeks
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
Number of Responders at the End-of-TP1
Time Frame: Up to 13 weeks
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
Percent of Responders at the End-of-TP1
Time Frame: Up to 13 weeks
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
Proportion of Subjects Surviving Through the Follow-up Period
Time Frame: Up to approximately 208 weeks
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
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
Up to approximately 42 weeks after the time of first investigational product administration
Mean Pre-dose C1-esterase Inhibitor Functional Activity
Time Frame: Up to 13 weeks
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
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
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
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
Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CSL Behring

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 6, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 20, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSL842_3001
  • 2017-000348-17 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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