PMID- 21906811
OWN - NLM
STAT- MEDLINE
DCOM- 20120213
LR  - 20191210
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 33
IP  - 9
DP  - 2011 Sep
TI  - Monoclonal antibody TB-403: a first-in-human, Phase I, double-blind, dose 
      escalation study directed against placental growth factor in healthy male 
      subjects.
PG  - 1142-9
LID - 10.1016/j.clinthera.2011.08.007 [doi]
AB  - BACKGROUND: TB-403 (RO5323441) is a humanized monoclonal antibody directed 
      against placental growth factor (PlGF). Preclinical studies have demonstrated 
      that targeting PlGF can result in significant inhibition of tumor growth and 
      metastasis. OBJECTIVES: The purpose of this study was to assess the safety 
      profile, tolerability, and pharmacokinetics of TB-403, developed for the 
      treatment of solid tumors. METHODS: Healthy male subjects were exposed to a 
      single intravenous infusion of TB-403 or placebo. Blood samples for hematology, 
      clinical chemistry, coagulation factors, and urinalysis were collected; vital 
      signs and ECGs were recorded; and serial blood samples were drawn for 
      pharmacokinetic and immunogenicity measurements and circulating levels of 
      pharmacodynamics markers PlGF and (VEGF) vascular endothelial growth factor. 
      Sixteen subjects received either placebo or TB-403 at doses ranging from 0.3 to 
      5.0 mg/kg. RESULTS: Mild (grade 1 or 2) nasopharyngitis, headache, neck pain, and 
      joint pain were the most frequently reported adverse events (AEs). There were no 
      serious AEs in the study, and none of the AEs led to withdrawal. None of the 
      safety laboratory assessments was considered clinically significant, and none was 
      reported as an AE. There were no apparent differences in terms of safety profiles 
      among the 3 dose levels of active treatment compared with placebo. Clearance, 
      volume of distribution, and terminal t((1/2)) (mean values) for TB-403 in all 3 
      cohorts were in the range of 4.2 to 4.9 (mL/d/kg), 56 to 79 (mL/kg), and 8 to 13 
      (days), respectively. CONCLUSION: The highest dose of TB-403 (5.0 mg/kg) was well 
      tolerated in this study of a single intravenous infusion to healthy males. This 
      result allowed a higher starting dose level in a subsequent Phase I study in 
      cancer patients, the patient population for which this antibody is developed.
CI  - Copyright (c) 2011 Elsevier HS Journals, Inc. All rights reserved.
FAU - Martinsson-Niskanen, Titti
AU  - Martinsson-Niskanen T
AD  - BioInvent International AB, Lund, Sweden. titti.martinsson.niskanen@bioinvent.com
FAU - Riisbro, Rikke
AU  - Riisbro R
FAU - Larsson, Leonard
AU  - Larsson L
FAU - Winstedt, Lena
AU  - Winstedt L
FAU - Stenberg, Yvonne
AU  - Stenberg Y
FAU - Pakola, Steve
AU  - Pakola S
FAU - Stassen, Jean-Marie
AU  - Stassen JM
FAU - Glazer, Steven
AU  - Glazer S
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110908
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (PGF protein, human)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 144589-93-5 (Placenta Growth Factor)
RN  - 46MVG4H2LF (TB-403)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal/administration & dosage/*adverse 
      effects/immunology/*pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/administration & dosage/*adverse 
      effects/immunology/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Placenta Growth Factor
MH  - Pregnancy Proteins/*antagonists & inhibitors/blood
MH  - Protein Binding
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors/blood
MH  - Young Adult
EDAT- 2011/09/13 06:00
MHDA- 2012/02/14 06:00
CRDT- 2011/09/13 06:00
PHST- 2011/06/01 00:00 [received]
PHST- 2011/08/10 00:00 [revised]
PHST- 2011/08/10 00:00 [accepted]
PHST- 2011/09/13 06:00 [entrez]
PHST- 2011/09/13 06:00 [pubmed]
PHST- 2012/02/14 06:00 [medline]
AID - S0149-2918(11)00545-5 [pii]
AID - 10.1016/j.clinthera.2011.08.007 [doi]
PST - ppublish
SO  - Clin Ther. 2011 Sep;33(9):1142-9. doi: 10.1016/j.clinthera.2011.08.007. Epub 2011 
      Sep 8.