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

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

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Biological: Immune Globulin Intravenous (Human), 10%

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Regional Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • San Francisco, California, United States, 94117
      • University of San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospitals
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University Medical Center
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose; 0.5 gm/kg at 5 days pre-transplant and 7 days post-transplant	Biological: Immune Globulin Intravenous (Human), 10%
Experimental: Middle Dose; 1.0 gm/kg at 5 days pre-transplant and 7 days post-transplant	Biological: Immune Globulin Intravenous (Human), 10%
Experimental: High Dose; 2.0 gm/kg at 5 days pre-transplant and 7 days post-transplant	Biological: Immune Globulin Intravenous (Human), 10%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Monitoring of crossmatch conversion rate after one infusion of IGIV

Secondary Outcome Measures

Outcome Measure
Graft survival and function
average percentage panel reactive antibodies (PRA) reduction
donor-specific unresponsiveness and allo-responsiveness in ESRD patients
subject survival
safety endpoints, including incidence rates of infection, adverse events, and hospitalizations

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Stanley C. Jordan, MD, Department of Pediatrics, Cedars-Sinai Medical Center

Publications and helpful links

General Publications

• 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. doi: 10.1097/01.TP.0000084200.40159.EC.
• 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. doi: 10.1034/j.1600-6143.2003.00121.x.
• 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. doi: 10.1097/01.TP.0000080685.31697.FC.
• 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. doi: 10.1111/j.1399-3046.2005.00256.x.
• 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. doi: 10.1097/01.TP.0000090868.88895.E0.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Study Completion (Actual): March 1, 2004

Study Registration Dates

• First Submitted: August 25, 2004
• First Submitted That Met QC Criteria: August 25, 2004
• First Posted (Estimate): August 26, 2004

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Immunoglobulins, Intravenous; Autoantibodies; Dose-Response Relationship, Immunologic; Transplantation, Homologous; HLA Antigens; Living Donors
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: DAIT IG03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: SDY356
   Information comments: ImmPort study identifier is SDY356
2. Study Protocol
   Information identifier: SDY356
   Information comments: ImmPort study identifier is SDY356
3. Study summary, -design, -demographics, -lab tests, -study files
   Information identifier: SDY356
   Information comments: ImmPort study identifier is SDY356