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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

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ClinicalTrials.gov Identifier: NCT03221842
Recruitment Status : Recruiting
First Posted : July 19, 2017
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
CSL Behring

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 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
Estimated Primary Completion Date : January 15, 2026
Estimated Study Completion Date : January 15, 2026

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Time to loss of response during Treatment Period 2 [ Time Frame: Up to approximately 25 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. Time to all-cause allograft failure through the follow-up period for both Treatment Period 1 responders and non-responders [ Time Frame: Up to approximately 208 weeks ]

    Allograft failure is defined as 1 of the following, whichever occurs first:

    • Allograft nephrectomy.
    • Permanent dialysis.
    • Return to the transplant waitlist.

  2. Percentage of subjects with response to treatment at the end of Treatment Period 1 [ Time Frame: Up to approximately 13 weeks ]
    Response is defined as an increase in eGFR.

  3. Percentage of subjects with sustained improvement of eGFR during Treatment Period 2 [ Time Frame: Up to approximately 25 weeks ]
    Sustained improvement is defined as an increase in eGFR

  4. Change from screening in Banff category scores at up to 38 weeks [ Time Frame: Screening and up to approximately 38 weeks ]
    Banff category scores are used to grade the histopathology of kidney allograft biopsies using a scoring system of 0 (best possible) to 3 (worst possible)

  5. Percentage of subjects with splenectomy during Treatment Period 1 and during Treatment Period 2 [ Time Frame: Up to approximately 38 weeks ]
  6. Percentage of subjects with allograft survival through the follow-up period [ Time Frame: Up to approximately 208 weeks ]
  7. Time to subject death through the follow-up period [ Time Frame: Up to approximately 208 weeks ]
  8. Percentage of subjects 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 ]
  9. Pre-dose C1-INH functional activity [ Time Frame: Day 1, approximately Week 12, and approximately Week 38 ]
  10. Time to maximum plasma concentration (Cmax) for C1-INH functional activity [ Time Frame: Up to 72 hours after dose ]
  11. Area under the plasma concentration time curve (AUC0-t) for C1-INH functional activity [ Time Frame: Up to 72 hours after dose ]


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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.

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


Contacts
Contact: Clinical Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com

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Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director CSL Behring

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT03221842     History of Changes
Other Study ID Numbers: CSL842_3001
2017-000348-17 ( EudraCT Number )
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Antibodies
Immunoglobulins
Complement C1s
Complement C1 Inhibitor Protein
Complement C1 Inactivator Proteins
Immunologic Factors
Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents