Kidney Failure, Chronic
Conditions
Keywords
Kidney Transplantation, Transplantation, Homologous, HLA Antigens, Autoantibodies, Immunoglobulins, Intravenous, Living Donors, Dose-Response Relationship, Immunologic
Brief 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.
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.
Interventions
BIOLOGICALImmune Globulin Intravenous (Human), 10%
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Monitoring of crossmatch conversion rate after one infusion of IGIV | — |
Secondary
| Measure | Time frame |
|---|---|
| safety endpoints, including incidence rates of infection, adverse events, and hospitalizations | — |
| subject survival | — |
| Graft survival and function | — |
| average percentage panel reactive antibodies (PRA) reduction | — |
| donor-specific unresponsiveness and allo-responsiveness in ESRD patients | — |
Countries
United States
Outcome results
None listed