Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation

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. Identifier: NCT01035593
Recruitment Status : Withdrawn (Recent improvements in clinical practice have reduced the apparent incidence of AMR in renal transplantation.)
First Posted : December 18, 2009
Last Update Posted : February 17, 2012
University of Wisconsin, Madison
Information provided by (Responsible Party):
Pharming Technologies B.V.

Brief Summary:
The purpose of this study will be to assess the safety, tolerability, and efficacy of rhC1INH in renal transplant recipients with biopsy-confirmed antibody-mediated rejection (AMR) within 30 days of renal transplantation. This study will combine the investigational drug rhC1INH with a standard regimen of plasmapheresis (PP) and intravenous immune globulin (IVIG) and compare this to PP and IVIG alone.

Condition or disease Intervention/treatment Phase
Graft Rejection Kidney Transplantation Procedure: plasmapheresis and IVIG Drug: recombinant C1 inhibitor Phase 2

Detailed Description:
This is an Investigator-initiated, prospective, open-label, randomized, adaptive design study to enroll 30 adult renal transplant recipients with biopsy-confirmed AMR within 30 days post transplantation. After informed consent is obtained and study eligibility is confirmed, subjects will be enrolled immediately after biopsy confirmation of AMR and positive donor specific antibody (DSA). Subjects will then be randomized into one of two treatment groups (SOC [control] or rhC1INH). An initial cohort of 8 subjects (3 SOC, 5 rhC1INH) will receive intensive safety monitoring of the coagulation system and for thromboembolic events.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation
Study Start Date : December 2010
Estimated Primary Completion Date : December 2011
Estimated Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Standard of Care (PP + IVIG)
Plasmapheresis and IVIG 100mg/kg every other day x 5 treatments
Procedure: plasmapheresis and IVIG
Plasmapheresis with either 5% human albumin or FFP replacement, plus IVIG 100mg/kg IV after each PP session, every other day x 5 treatments
Experimental: PP + IVIG + rhC1INH
Plasmapheresis + 100mg/kg IVIG every other day x 5 treatments plus rhC1Inh 100u/kg IV daily x 7 consecutive days (once daily on PP days, twice daily on non-PP days).
Drug: recombinant C1 inhibitor
100units/kg IV for seven consecutive days (once daily on PP/IVIG days, twice daily on non-PP/IVIG days).

Primary Outcome Measures :
  1. Efficacy will be defined as renal allograft survival 6 months following treatment for AMR. Renal allograft loss will be defined as either (1) subject death, (2) return to dialysis for greater than 30 days, or (3) re-transplantation. [ Time Frame: 6 month ]

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

Inclusion Criteria:

  • Recipients of renal transplantation within 30 days prior to enrollment.
  • AMR documented by light microscopic changes and immunohistochemical C4d staining on renal biopsy within 30 days post-transplant.
  • Positive DSA as detected by magnetic microbeads using a Luminex® system.
  • Age ≥ 18 years.
  • Women of child-bearing potential (CBP) must have negative pregnancy test at screening.
  • Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study and for 3 months following discontinuation of assigned treatment.
  • Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

  • Recipients of multi-organ transplants.
  • Recipients with previous early AMR.
  • Recipients with a known hypersensitivity to C1INH, rabbit anti-thymocyte globulin, or any rabbit protein.
  • History of malignancy within 3 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
  • Subjects who are positive for hepatitis C, hepatitis B surface antigen, or HIV at the time of transplant.
  • Subjects who are actively taking an investigational drug.
  • Subjects with a history of a psychological illness or condition that could interfere with the subject's ability to understand the requirements of the study.
  • Female subjects who are pregnant or nursing.
  • Subjects with hemodynamic instability, as defined by a mean arterial pressure (MAP) <60 mmHg or >110 mmHg; or requirement of vasopressors to maintain a MAP of 60 mmHg; or requirement of IV vasodilators for hypertensive emergency; or acute pulmonary edema.
  • Subjects with known active infection at the time of enrollment.
  • Biopsy-confirmed concurrent cellular rejection requiring polyclonal antibody therapy (i.e., all Grades other than Banff 1a and 1b will be excluded).

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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 identifier (NCT number): NCT01035593

United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Pharming Technologies B.V.
University of Wisconsin, Madison
Principal Investigator: Hans Sollinger, MD, PhD University of Wisconsin, Madison

Responsible Party: Pharming Technologies B.V. Identifier: NCT01035593     History of Changes
Other Study ID Numbers: C1 2201
First Posted: December 18, 2009    Key Record Dates
Last Update Posted: February 17, 2012
Last Verified: February 2012

Additional relevant MeSH terms:
Immunoglobulins, Intravenous
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Immunologic Factors
Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents