Improving Transplant Options of Highly Sensitized Recipients Using IGIV-C, 10%

Kidney Failure, Chronic Clinical Trial

Official title:

Evaluation of Immune Globulin Intravenous (Human), 10%, Manufactured by Chromatography Process (IGIV-C, 10%), as an Agent to Reduce Anti-HLA Antibodies and Improve Transplantation Results in Cross Match Positive Living Donor Kidney Allograft Recipients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00090194
• Other study ID #: DAIT IG03
• Status: Terminated
• Phase: Phase 2
• First received: August 25, 2004
• Last updated: January 10, 2017
• Start date: June 2003
• Est. completion date: March 2004

Study information

• Verified date: January 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• 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 is to determine if IGIV-C, 10% will be effective in converting a donor-recipient crossmatch status from positive to negative. The crossmatch test is used to determine if the donor tissue and recipient tissue are compatible. The study will also evaluate if IGIV-C, 10% will allow successful kidney transplantation in a patient who otherwise would not be able to receive a transplant. Three dose levels of IGIV-C, 10% will be evaluated to determine what dose level is most effective.

Description:

Kidney transplantation has emerged as the treatment of choice for patients with end-stage renal disease (ESRD). Preliminary data suggest that IGIV therapy could have significant benefits in modifying allograft rejection episodes, stabilizing long-term allograft function, and reducing ischemia/reperfusion injury.

Qualified patients will have an in-vitro assessment of the ability of IGIV-C, 10% to convert the donor-specific crossmatch (cytotoxic assay) from positive to negative. Those patients with successful in-vitro conversion of the donor-specific crossmatch assay will be randomized to receive IGIV-C, 10% intravenously at a dose of either 2 gm/kg, 1 gm/kg, or 0.5 gm/kg. IGIV-C, 10% will be administered 3 to 5 days prior to planned transplantation and, if transplantation is successful, 7 days post-transplant. If after receiving the IGIV-C infusion the donor-specific crossmatch reveals that cell death has fallen to 20% or less above background, the crossmatch will be considered negative. If after receiving one infusion the crossmatch remains positive, additional IGIV-C infusions may be administered at one-month intervals, up to 4 infusions. A repeat crossmatch must be obtained after each infusion. Patients will be followed for 12 months post-transplant. Concomitant therapy will include a standard immunosuppression regimen of mycophenolate mofetil, tacrolimus, and prednisone following induction therapy with thymoglobulin.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: March 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 70 Years

Eligibility

Inclusion Criteria for Recipient:

• End-stage renal disease

• No known contraindications for therapy with IGIV-C, 10%

• Have identified a living kidney donor

• Positive crossmatch with the intended donor

• Parent or guardian willing to provide consent, if applicable

Exclusion Criteria for Recipient:

• Pregnant or breastfeeding

• Women of child-bearing age who are not willing or able to practice approved methods of contraception

• HIV infection

• Hepatitis B or hepatitis C infection

• History of positive tuberculin skin test

• Selective IgA deficiency, known anti-IgA antibodies, or history of severe allergy to any part of the clinical trial material

• Have received or will receive multiple organ transplants

• Any licensed or investigational live attenuated vaccine within 2 months of the screening visit

• Patients deemed unable to comply with the protocol

• Heart attack within 1 year of screening

• History of clinically significant thrombotic episodes or active peripheral vascular disease

• Investigational agents within 4 weeks of study entry

Inclusion Criteria for Donor:

• Positive donor-specific crossmatch with the intended recipient

• ECOG performance status 0 or 1

• Excellent health

• Acceptable laboratory parameters

• Compatible blood type

• Normal heart and lung evaluations

• Parent or guardian willing to provide consent, if applicable

Study Design

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

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Biological:
• Immune Globulin Intravenous (Human), 10%

Locations

Country	Name	City	State
United States	University of Michigan Hospitals	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Medical Branch	Galveston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	UCLA Medical Center	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Banner Good Samaritan Regional Medical Center	Phoenix	Arizona
United States	Rhode Island Hospital	Providence	Rhode Island
United States	California Pacific Medical Center	San Francisco	California
United States	University of San Francisco	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	Washington Hospital Center	Washington	District of Columbia
United States	University of Massachusetts Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Akalin E, Ames S, Sehgal V, Fotino M, Daly L, Murphy B, Bromberg JS. Intravenous immunoglobulin and thymoglobulin facilitate kidney transplantation in complement-dependent cytotoxicity B-cell and flow cytometry T- or B-cell crossmatch-positive patients. Transplantation. 2003 Nov 27;76(10):1444-7. — View Citation

Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant. 2003 Jun;3(6):653-64. Review. — View Citation

Jordan SC, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D. Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation. 2003 Aug 27;76(4):631-6. — View Citation

Jordan SC, Vo AA, Toyoda M, Tyan D, Nast CC. Post-transplant therapy with high-dose intravenous gammaglobulin: Applications to treatment of antibody-mediated rejection. Pediatr Transplant. 2005 Apr;9(2):155-61. Review. — View Citation

Zachary AA, Montgomery RA, Ratner LE, Samaniego-Picota M, Haas M, Kopchaliiska D, Leffell MS. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation. 2003 Nov 27;76(10):1519-25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Monitoring of crossmatch conversion rate after one infusion of IGIV			No
Secondary	Graft survival and function
Secondary	average percentage panel reactive antibodies (PRA) reduction
Secondary	donor-specific unresponsiveness and allo-responsiveness in ESRD patients
Secondary	subject survival
Secondary	safety endpoints, including incidence rates of infection, adverse events, and hospitalizations

External Links

•   Division of Allergy, Immunology, and Transplantation (DAIT)
•   National Institute of Allergy and Infectious Diseases (NIAID)