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.

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.

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