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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01035593
• Other study ID #: C1 2201
• Status: Withdrawn
• Phase: Phase 2
• First received: December 16, 2009
• Last updated: February 15, 2012
• Start date: December 2010
• Est. completion date: December 2011

Study information

• Verified date: February 2012
• Source: Pharming Technologies B.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Rejection
• Kidney Transplantation

Intervention

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

Drug:
• recombinant C1 inhibitor
100units/kg IV for seven consecutive days (once daily on PP/IVIG days, twice daily on non-PP/IVIG days).

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Pharming Technologies B.V.	University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 month	Yes