NCT03221842

Brief 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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2017

Typical duration for phase_3

Geographic Reach
7 countries

26 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 17, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 19, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

November 6, 2017

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 20, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 20, 2021

Completed
12 months until next milestone

Results Posted

Study results publicly available

January 18, 2022

Completed
Last Updated

July 29, 2022

Status Verified

July 1, 2022

Enrollment Period

3.2 years

First QC Date

July 17, 2017

Results QC Date

November 18, 2021

Last Update Submit

July 25, 2022

Conditions

Antibody-mediated Rejection

Keywords

Antibody-mediated kidney transplant rejectionRenal

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (13)

  • Number of Participants With All-cause Allograft Failure During TP2

    Up to 38 weeks

  • Percent of Participants With All-cause Allograft Failure During TP2

    Up to 38 weeks

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

    Baseline and 13 weeks

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

    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

    Up to 38 weeks

  • +8 more secondary outcomes

Study Arms (2)

C1-INH

EXPERIMENTAL

C1-esterase inhibitor

Drug: C1-esterase inhibitor

Placebo

PLACEBO COMPARATOR

Excipients of C1-INH plus albumin

Drug: Placebo

Interventions

C1-esterase inhibitorDRUG

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

Also known as: C1-INH
C1-INH
PlaceboDRUG

Excipients of C1-INH plus albumin

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

University of Alabama Hospital (at Birmingham)

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

California Pacific

San Francisco, California, 94115, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

University of Illinois Chicago

Chicago, Illinois, 60612, United States

Location

Brigham & Women's

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic (Rochester)

Rochester, Minnesota, 55905, United States

Location

St. Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

NYU

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705-2281, United States

Location

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000, Belgium

Location

CHU de Bordeaux. Hôpital Pellegrin

Bordeaux, 33000, France

Location

CHU de Grenoble - Hôpital Michalon

Grenoble, 38043, France

Location

Centre Regional Hospitalier Universitaire de Lille

Lille, 59000, France

Location

Hospital Edouard Herriot Lyon

Lyon, 69003, France

Location

Hopital saint Louis Paris

Paris, 75010, France

Location

Necker Hospital

Paris, 75743, France

Location

CHU Rangueil

Toulouse, 31059, France

Location

Charite Berline

Berlin, 10117, Germany

Location

Leiden University Medical Center

Leiden, 2300, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Guy's Hospital

London, SE19RT, United Kingdom

Location

Related Publications (1)

  • Viklicky O, Slatinska J, Novotny M, Hruba P. Developments in immunosuppression. Curr Opin Organ Transplant. 2021 Feb 1;26(1):91-96. doi: 10.1097/MOT.0000000000000844.

    PMID: 33332922DERIVED

MeSH Terms

Interventions

Complement C1 Inhibitor Protein

Intervention Hierarchy (Ancestors)

GlycoproteinsGlycoconjugatesCarbohydratesComplement C1 Inactivator ProteinsSerpinsPeptidesAmino Acids, Peptides, and ProteinsComplement Inactivator ProteinsComplement System ProteinsImmunoproteinsBlood ProteinsProteins

Limitations and Caveats

The Sponsor terminated the study due to futility of enrolment. Because of the study termination, there are limitations in interpreting analyses and efficacy results based on small numbers of subjects. No subject reached the 48-month follow-up endpoint.

Results Point of Contact

Title
Study Director
Organization
CSL Behring
clinicaltrials@cslbehring.com
610-878-4000

Study Officials

  • Program Director

    CSL Behring

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Randomized-withdrawal
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 17, 2017

First Posted

July 19, 2017

Study Start

November 6, 2017

Primary Completion

January 20, 2021

Study Completion

January 20, 2021

Last Updated

July 29, 2022

Results First Posted

January 18, 2022

Record last verified: 2022-07

Data Sharing

IPD Sharing
Will not share

Locations

BE(1)US(13)FR(7)NL(1)DE(1)ES(2)GB(1)