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

Primary Purpose

Graft Rejection, Kidney Transplantation

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
plasmapheresis and IVIG
recombinant C1 inhibitor
Sponsored by
Pharming Technologies B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Rejection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care (PP + IVIG)

PP + IVIG + rhC1INH

Arm Description

Plasmapheresis and IVIG 100mg/kg every other day x 5 treatments

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).

Outcomes

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.

Secondary Outcome Measures

Full Information

First Posted
December 16, 2009
Last Updated
February 15, 2012
Sponsor
Pharming Technologies B.V.
Collaborators
University of Wisconsin, Madison
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1. Study Identification

Unique Protocol Identification Number
NCT01035593
Brief Title
Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation
Official Title
Recombinant Human C1 Inhibitor for the Treatment of Early Antibody-Mediated Rejection in Renal Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Recent improvements in clinical practice have reduced the apparent incidence of AMR in renal transplantation.
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2011 (Anticipated)
Study Completion Date
December 2011 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharming Technologies B.V.
Collaborators
University of Wisconsin, Madison

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Rejection, Kidney Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Sollinger, MD, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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