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

This study has been withdrawn prior to enrollment.
(Recent improvements in clinical practice have reduced the apparent incidence of AMR in renal transplantation.)
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
Pharming Technologies B.V.
ClinicalTrials.gov Identifier:
NCT01035593
First received: December 16, 2009
Last updated: February 15, 2012
Last verified: February 2012
  Purpose

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 Intervention Phase
Graft Rejection
Kidney Transplantation
Procedure: plasmapheresis and IVIG
Drug: recombinant C1 inhibitor
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation

Resource links provided by NLM:


Further study details as provided by Pharming Technologies B.V.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: December 2010
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035593

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

No publications provided

Responsible Party: Pharming Technologies B.V.
ClinicalTrials.gov Identifier: NCT01035593     History of Changes
Other Study ID Numbers: C1 2201
Study First Received: December 16, 2009
Last Updated: February 15, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 24, 2014