SAFETY, TOLERANCE, EFFICACY, AND BIOLOGICAL HALF-LIFE OF 10% GAMMAGARD-SD

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Purpose: This is a randomized, double-blind study comparing the safety and patient acceptability of 10% Gammagard-SD to a licensed IGIV product, 10%Gamimune-N. Background: Intravenous gammaglobulin (IGIV) preparations have been tested in the US since 1975 and ten have been licensed since 1981, seven of which are currently available. The efficacy of IGIV in preventing infections in patients with primary disorders of humoral immunity is well accepted, though it has never been subjected to a controlled double-blind study. A study comparing IGIV to placebo would be considered unethical, though it is possible to compare new products to those that have been licensed for use. In the past several years efforts have focused on developing products with increased safety, especially with regard to the risk of transmitting viral infections such as Hepatitis C. This study proposes to compare the safety and efficacy of a newly licensed 10% solvent/detergent IGIV preparation, Gammagard-SD to a licensed preparation, 10% Gamimune-N. Gammagard-SD is a sterile, preservative-free, lyophilized preparation of unmodified human polyvalent immunoglobulins manufactured by Baxter Healthcard Corporation, Hyland division.. It is prepared from ISG made from a pool of at least 1000 donors. Donors are tested for HIV, HBsAg, Hepatitis C antibody, and increased levels of ALT before being accepted into the pool. The ISG is prepared by the same Cohn fractionation process used for all of the currently licensed products. The Cohn fraction III supernatant is subjected to a viral inactivation step consisting of treatment with solvent (0.3% tri-n-butyl phosphate) and two detergents, oxtoxynol 9 (Triton X-100) and polysorbate 80 (Tween 80) using a process similar to that developed in the New York Blood Center and currently used for one other licensed IGIV preparation and other blood products. After addition of the solvent and detergents the solution is treated to remove all but trace amounts of the additives. The final lyophilized product, when reconstituted to 5% IgG, contains 0.3 gm/dl human albumin, 0.15 M NaCl, 0.11 M dextrose, 0.3 M glycine, 0.2 g/dl polyethylene glycol, and residual levels of IgM and IgA. Gammagard-SD has one of the lowest IgA levels of any product. Methods: This is a randomized, double-blind study comparing the safety and patient acceptability of 10% Gammagard-SD to a licensed IGIV product, 10%Gamimune.-N. It is a multicenter phase IV study intended to enroll approximately 30 adults and children in three centers. All patients will have well characterized disorders of humoral immunity and require gammaglobulin infusions for infection prophylaxis. All patients will have received at least six infusions of IGIV and are known to tolerate the currently available preparations. IgA deficient patients who are at risk for making anti-IgA antibodies and pregnant patients will be excluded. If they meet the entry requirements they will be entered to receive a minimum of six infusions of each of the products at the dose and frequency given during the three months preceding the study. The gammaglobulin will be put in IV bags by the pharmacy so that neither the patient nor the investigators will know which preparation is used. The IGIV will be infused at an initial rate of 1 cc/kg/hr and the rate increased to a maximum of 4.8 cc/kg/hr at 15 minute intervals unless adverse reactions occur.