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

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