Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers

Abstract

A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax(®) (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18-50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA+0.5mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA+0.25mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA+0.5mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA+0.25mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Subject Disposition Through Day 84. A total of 237 subjects were screened within 28 days of enrollment in the study. Subjects who met the entry criteria (N=105) were randomized to 1 of 6 study groups at a ratio of 6:6:6:6:6:5: BioThrax, AV7909 Formulation 1, AV7909 Formulation 2, AV7909 Formulation 3, AV7909 Formulation 4, or saline placebo. All randomized subjects received at least 1 injection of investigational product and were included in the safety population. One hundred subjects completed the study.

Figure 2

Injection Site Reactions Recorded by Subjects on Diary Cards After the First Injection. A web-enabled subject diary was to be completed by each subject for 7 days after the injection. Data were solicited on the following injection site reactions: redness, swelling, tenderness, injection site pain, injection site itching, and arm motion limitation. Each bar shows the total percentage of subjects with injection site reactions on the study day and the percentage of subjects with reactions of each severity grade (mild, moderate, severe) as applicable. Data are shown by the most severe grade if a subject had multiple events with different grades.

Figure 2

Injection Site Reactions Recorded by Subjects on Diary Cards After the First Injection. A web-enabled subject diary was to be completed by each subject for 7 days after the injection. Data were solicited on the following injection site reactions: redness, swelling, tenderness, injection site pain, injection site itching, and arm motion limitation. Each bar shows the total percentage of subjects with injection site reactions on the study day and the percentage of subjects with reactions of each severity grade (mild, moderate, severe) as applicable. Data are shown by the most severe grade if a subject had multiple events with different grades.

Figure 3

Anthrax Toxin Neutralizing Antibody Titers. Blood samples for measurement of toxin neutralizing antibody titers (TNA NF50) were collected on Days 0 (pre-injection), 7, 14 (pre- injection), 21, 28, 35, 42, 56, 70, and 84. Geometric mean and 95% CIs are shown for each study day. TNA = toxin neutralizing antibody; NF50 = 50% neutralization factor