Anthrax-rPA: Safety, Tolerability, Immunogenicity
The primary objective is to determine the tolerability and safety, from days 0 to 210, of escalating doses of rPA either with or without Alhydrogel (an adjuvant; used to increase the action of the principle drug) given in a two-dose, intramuscular regimen to health adults. The secondary objective is to evaluate antibody responses to rPA, from days 0 to 210, following one of four escalating doses of vaccine given with and without Alhydrogel given in a two-dose series to healthy adults, and to compare immune responses following rPA with those following BioThrax (tm) given by either the intramuscular or SQ route. The tertiary objective is to describe the antibody kinetics following vaccination. This information will be used to determine the most probable optimal dose of rPA and/or Alhydrogel that is safe, well tolerated, and maximally immunogenic for use in future phase II trials.
Biological: Recombinant Protective Antigen, Anthrax Vaccine Adsorbed
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Prevention
|Official Title:||A Phase I, Dose-Escalating Study to Assess the Safety, Tolerability, and Immunogenicity of Recombinant Anthrax Protective Antigen Vaccine (rPA) Administered in Two Intramuscular Doses to Healthy Adults|
|Study Start Date:||July 2003|
|Estimated Study Completion Date:||August 2005|
This Phase I, Dose-Escalating clinical study is designed to examine the immunologic response to rPA in the presence and absence of Alhydrogel at the 2 lowest dose levels. The study will investigate whether use of an aluminum-based adjuvant results in an increase in the magnitude or the duration of the antibody response, thus providing information on the necessity of aluminum-based adjuvants in formulations used in the phase II clinical trials. The rationale for the use of BioThrax by two administration routes in this trial is to allow for preliminary comparisons of the immune response following the currently available vaccine to the response following the new recombinant product. Approximately 80 outpatient community volunteers from the Baltimore-Washington area aged 18-40 years will be recruited on the basis of good health, expressed interest in the study, and availability for follow-up as determined at a preliminary interview. Each eligible subject will be enrolled in 1 of 4 study groups, each with three arms, for 7 months. The subjects' randomly assigned and double-masked to Arms A and B will have a 30 day screening period in which they will receive two doses of IM rPA or IM rPA+Alhydrogel or IM BioThrax one month apart, with follow up days on 1, 2, 7, 14, 28, 29, 30, 35, 42, 120, and 210. The subjects randomly assigned, but unmasked, to arms 1-C or 2-C will receive 3 doses of SQ BioThrax at 14 day intervals with follow up on days 1, 2, 7, 14, 15, 16, 21, 28, 29, 30, 35, 42, 120 and 210. The information gathered from the study objectives will be used to determine the most probable optimal doses of rPA +/- Alhydrogel that are safe, well tolerated, and maximally immunogenic for use in future phase II trials.
|United States, Maryland|
|University of Maryland School of Medicine|
|Baltimore, Maryland, United States, 21201|