PMID- 24913160
OWN - NLM
STAT- MEDLINE
DCOM- 20150909
LR  - 20211021
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 58
IP  - 9
DP  - 2014 Sep
TI  - Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal 
      antibodies against botulinum toxin A.
PG  - 5047-53
LID - 10.1128/AAC.02830-14 [doi]
AB  - Botulinum neurotoxin A is a category A bioterrorism agent. Current antitoxin 
      therapies are scarce and produce adverse reactions. XOMA 3AB consists of 3 IgG1 
      monoclonal antibodies (MAbs), each with a distinct human or humanized variable 
      region, which bind to distinct epitopes on botulinum neurotoxin serotype A. This 
      first-in-human study evaluated the safety and pharmacokinetics (PK) of escalating 
      doses of XOMA 3AB administered intravenously (i.v.) to healthy adults. In this 
      double-blind placebo-controlled dose escalation study, 3 cohorts of 8 healthy 
      subjects received a single intravenous dose of XOMA 3AB or placebo at a 3:1 
      ratio. Follow-up examinations included physical examinations, hematology and 
      chemistry blood tests, electrocardiograms, and pharmacokinetics. Pharmacokinetic 
      parameters were estimated using noncompartmental methods. There were no infusion 
      discontinuations or hypersensitivity reactions. Two or more subjects experienced 
      headache, hyperglycemia, or anemia; none was dose related. All adverse events 
      (AEs) were mild to moderate except for an episode of exercise-induced elevation 
      of a subject's creatine phosphokinase (CPK) level, unrelated to XOMA 3AB. 
      Concentration-time plots demonstrated a peak in MAb concentrations 1 to 2 h after 
      completion of the infusion, after which the levels declined in a biexponential 
      decay pattern for all analytes. For each MAb, the maximum concentration of drug 
      in serum (Cmax) and the area under the concentration-time curve from 0 to 
      infinity (AUCinf) increased as the dose increased. Clearance of the humanized 
      mouse MAb was more rapid than that of the two fully human MAbs, particularly at 
      the lowest dose. None of the MAbs was immunogenic. At the doses administered, 
      XOMA 3AB was well tolerated. These safety findings support further investigation 
      of XOMA 3AB as a potential agent for botulism treatment and postexposure 
      prophylaxis. (This study has been registered at ClinicalTrials.gov under 
      registration no. NCT01357213.).
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Nayak, S U
AU  - Nayak SU
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Griffiss, J M
AU  - Griffiss JM
AD  - Clinical RM, Inc., Hinckley, Ohio, USA.
FAU - McKenzie, R
AU  - McKenzie R
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Fuchs, E J
AU  - Fuchs EJ
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Jurao, R A
AU  - Jurao RA
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - An, A T
AU  - An AT
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Ahene, A
AU  - Ahene A
AD  - XOMA Corporation, Berkeley, California, USA.
FAU - Tomic, M
AU  - Tomic M
AD  - XOMA Corporation, Berkeley, California, USA.
FAU - Hendrix, C W
AU  - Hendrix CW
AD  - Johns Hopkins University, Baltimore, Maryland, USA.
FAU - Zenilman, J M
AU  - Zenilman JM
AD  - Johns Hopkins University, Baltimore, Maryland, USA jzenilma@jhmi.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT01357213
GR  - HHSN272200800026C/AI/NIAID NIH HHS/United States
GR  - UL1 TR000424/TR/NCATS NIH HHS/United States
GR  - UL1 TR 000424-06/TR/NCATS NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20140609
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antibodies, Monoclonal)
RN  - EC 3.4.24.69 (Botulinum Toxins, Type A)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antibodies, Monoclonal/*adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Botulinum Toxins, Type A/*antagonists & inhibitors
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Young Adult
PMC - PMC4135817
EDAT- 2014/06/11 06:00
MHDA- 2015/09/10 06:00
PMCR- 2015/03/01
CRDT- 2014/06/11 06:00
PHST- 2014/06/11 06:00 [entrez]
PHST- 2014/06/11 06:00 [pubmed]
PHST- 2015/09/10 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - AAC.02830-14 [pii]
AID - 02830-14 [pii]
AID - 10.1128/AAC.02830-14 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2014 Sep;58(9):5047-53. doi: 10.1128/AAC.02830-14. 
      Epub 2014 Jun 9.