PMID- 24613523
OWN - NLM
STAT- MEDLINE
DCOM- 20140910
LR  - 20140402
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 32
IP  - 19
DP  - 2014 Apr 17
TI  - Phase 3 trial evaluating the immunogenicity and safety of a three-dose BioThrax(R) 
      regimen for post-exposure prophylaxis in healthy adults.
PG  - 2217-24
LID - S0264-410X(14)00136-4 [pii]
LID - 10.1016/j.vaccine.2014.01.073 [doi]
AB  - BACKGROUND: This study was conducted to support licensure of a post-exposure 
      prophylaxis indication for BioThrax((R)) (anthrax vaccine adsorbed) concurrent with 
      antimicrobials for individuals exposed to aerosolized anthrax spores. METHODS: 
      The immunogenicity and safety of a three-dose regimen (0, 2, and 4 weeks) of 
      BioThrax administered subcutaneously (SC) were evaluated in 200 healthy adults 
      18-65 years of age. Toxin-neutralizing antibody (TNA) was expressed as 50% 
      neutralization factor (NF50) at predetermined time points through Day 100. Safety 
      was assessed by physical examinations, vital signs, solicited local and systemic 
      reactions using web-enabled subject diaries, in-clinic solicited reactions, and 
      unsolicited adverse events (AEs). RESULTS: The prospectively defined success 
      criteria for the primary and secondary endpoints were met. This required the 
      lower bound of the 95% confidence interval (CI) for the proportion of subjects 
      with a TNA NF50 value to be greater than 40% at Day 63 (primary), Day 70 
      (secondary) and Days 63-100 (secondary). At Day 63, 71% of subjects achieved a 
      TNA NF50 threshold value >/= 0.56, with a lower bound of the 95% CI >/= 40% (64%). 
      The percentage of subjects achieving a TNA NF50 threshold value >/= 0.56 at Day 70 
      was 58% (95% CI: 50%, 65%), and the mean value on Days 63-100 (inclusive) was 53% 
      (95% CI: 41%, 55%). The threshold TNA NF50 value of 0.56 was developed from 
      previous rabbit challenge and human immunogenicity studies. No related serious 
      AEs occurred during the study, and no subjects withdrew from the study because of 
      an AE. Tenderness and pain at the injection site were recorded most often in 
      subject diaries following vaccination. CONCLUSIONS: BioThrax, administered as 
      three SC doses at 0, 2, and 4 weeks, was well tolerated. The prospectively 
      defined success criteria for TNA levels on Days 63, 70, and 63-100 were achieved.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Hopkins, Robert J
AU  - Hopkins RJ
AD  - Clinical Development, Emergent BioSolutions, Gaithersburg, MD, USA. Electronic 
      address: HopkinsR@ebsi.com.
FAU - Howard, Cris
AU  - Howard C
AD  - Clinical Development, Emergent BioSolutions, Gaithersburg, MD, USA.
FAU - Hunter-Stitt, Ericka
AU  - Hunter-Stitt E
AD  - Clinical Development, Emergent BioSolutions, Gaithersburg, MD, USA.
FAU - Kaptur, Paulina E
AU  - Kaptur PE
AD  - Corporate Clinical and Medical Affairs, Emergent BioSolutions, Gaithersburg, MD, 
      USA.
FAU - Pleune, Brett
AU  - Pleune B
AD  - Regulatory Affairs, Emergent BioSolutions, Gaithersburg, MD, USA. Electronic 
      address: PleuneB@ebsi.com.
FAU - Muse, Derek
AU  - Muse D
AD  - Jean Brown Research, Salt Lake City, UT, USA.
FAU - Sheldon, Eric
AU  - Sheldon E
AD  - Miami Research Associates, South Miami, FL, USA.
FAU - Davis, Matthew
AU  - Davis M
AD  - Rochester Clinical Research Inc., Rochester, NY, USA.
FAU - Strout, Cynthia
AU  - Strout C
AD  - Coastal Carolina Research Center, Mount Pleasant, SC, USA.
FAU - Vert-Wong, Katya
AU  - Vert-Wong K
AD  - Emergent BioSolutions, Gaithersburg, MD, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20140306
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Anthrax Vaccines)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Biothrax)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anthrax/*prevention & control
MH  - Anthrax Vaccines/administration & dosage/adverse effects/immunology/*therapeutic 
      use
MH  - Antibodies, Bacterial/blood
MH  - Antibodies, Neutralizing/blood
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunization, Secondary
MH  - Male
MH  - Middle Aged
MH  - *Post-Exposure Prophylaxis
MH  - Young Adult
OTO - NOTNLM
OT  - Anthrax
OT  - BioThrax((R))
OT  - Clinical trial
OT  - Immunogenicity
OT  - Post-exposure prophylaxis
OT  - Vaccine
EDAT- 2014/03/13 06:00
MHDA- 2014/09/11 06:00
CRDT- 2014/03/12 06:00
PHST- 2013/11/20 00:00 [received]
PHST- 2014/01/23 00:00 [revised]
PHST- 2014/01/28 00:00 [accepted]
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/09/11 06:00 [medline]
AID - S0264-410X(14)00136-4 [pii]
AID - 10.1016/j.vaccine.2014.01.073 [doi]
PST - ppublish
SO  - Vaccine. 2014 Apr 17;32(19):2217-24. doi: 10.1016/j.vaccine.2014.01.073. Epub 
      2014 Mar 6.