A statistical demonstration of a serious infection rate of less than 1 per person-year is adequate to provide substantial evidence of efficacy in clinical trials of investigational human immune globulin intravenous (IGIV) products, CBER says.
Sponsors of IGIV products may be able to run pivotal clinical trials using various types of designs, CBER says in a new guidance, which finalizes a draft released in November 2005.
IGIV products are used as replacement therapy for primary humoral immunodeficiency. They are prepared from large pools of plasma collected from numerous individual healthy donors, so they contain antibodies against many infectious agents.
At an FDA Blood Products Advisory Committee meeting in 1999, the agency suggested a pivotal trial design using a prospective, randomized, double-blind, parallel, positive-control, noninferiority study in 80 subjects with a documented history of primary humoral immunodeficiency in which the safety and efficacy of the test product would be compared with that of a U.S.-licensed IGIV product. Sponsors were advised to evaluate efficacy by comparing the serious infection rate in each group over a year’s time.
Since then, CBER has determined that other approaches may work. For example, it suggested alternative clinical trial design proposals involving testing in fewer subjects in an open-label, single-arm trial compared with a statistically modeled historical control might be sufficient to provide evidence of safety and efficacy.
The guidance can be accessed at www.fda.gov/cber/gdlns/igivimmuno.htm.