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

NCT01035593 | Withdrawn Phase 2 DMC

• 1 other identifier: C1 2201
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Rejection; Kidney Transplantation

Outcome Measures

Primary Outcomes (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.

  6 month

Study Arms (2)

Standard of Care (PP + IVIG)

ACTIVE COMPARATOR

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

Procedure: plasmapheresis and IVIG

PP + IVIG + rhC1INH

EXPERIMENTAL

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

Interventions

plasmapheresis and IVIG PROCEDURE

Plasmapheresis with either 5% human albumin or FFP replacement, plus IVIG 100mg/kg IV after each PP session, every other day x 5 treatments

Standard of Care (PP + IVIG)

recombinant C1 inhibitor DRUG

100units/kg IV for seven consecutive days (once daily on PP/IVIG days, twice daily on non-PP/IVIG days).

PP + IVIG + rhC1INH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pharming Technologies B.V.: lead
• University of Wisconsin, Madison: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Interventions

Plasmapheresis; Immunoglobulins, Intravenous; conestat alfa

Intervention Hierarchy (Ancestors)

Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hans Sollinger, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 18, 2009
• Study Start: December 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 17, 2012

Record last verified: 2012-02

Locations

US (1)