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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03221842
Recruitment Status : Terminated (The study was terminated early due to futility of enrolment and not for safety reasons.)
First Posted : July 19, 2017
Results First Posted : January 18, 2022
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Description
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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).

Condition or disease Intervention/treatment Phase
Antibody-mediated Rejection Drug: C1-esterase inhibitor Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Randomized-withdrawal
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 6, 2017
Actual Primary Completion Date : January 20, 2021
Actual Study Completion Date : January 20, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: C1-INH
C1-esterase inhibitor
 Drug: C1-esterase inhibitor
C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution
Other Name: C1-INH
Placebo Comparator: Placebo
Excipients of C1-INH plus albumin
 Drug: Placebo
Excipients of C1-INH plus albumin


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Percent of Participants With All-cause Allograft Failure During TP2 [ Time Frame: Up to 38 weeks ]
  3. Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1) [ Time Frame: Baseline and 13 weeks ]
  4. Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2 [ Time Frame: Baseline and 38 weeks ]
  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 ]
  11. 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.

  12. 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.

  13. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03221842


Locations
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Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Program Director CSL Behring
  Study Documents (Full-Text)

Documents provided by CSL Behring:
Study Protocol  [PDF] January 31, 2020
Statistical Analysis Plan  [PDF] December 10, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03221842    
Other Study ID Numbers: CSL842_3001
2017-000348-17 ( EudraCT Number )
First Posted: July 19, 2017    Key Record Dates
Results First Posted: January 18, 2022
Last Update Posted: July 29, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CSL Behring:
Antibody-mediated kidney transplant rejection
Renal
Additional relevant MeSH terms:
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Complement C1s
Complement C1 Inhibitor Protein
Complement C1 Inactivator Proteins
Immunologic Factors
 Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents