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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Kidney Failure, Chronic

Intervention / Treatment
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* Biological: Immune Globulin Intravenous (Human), 10%


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitoring of crossmatch conversion rate after one infusion of IGIV |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, Transplantation, Homologous, HLA Antigens, Autoantibodies, Immunoglobulins, Intravenous, Living Donors, Dose-Response Relationship, Immunologic