PMID- 27545119
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20191210
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 6
IP  - 3
DP  - 2017 May
TI  - A Randomized Phase 1 Study to Assess the Safety and Pharmacokinetics of the 
      Subcutaneously Injected Anti-LIGHT Antibody, SAR252067.
PG  - 292-301
LID - 10.1002/cpdd.295 [doi]
AB  - LIGHT, a member of the tumor necrosis factor superfamily, is potentially involved 
      in mucosal inflammation associated with inflammatory bowel disease. The safety 
      and pharmacokinetics of the fully human monoclonal anti-LIGHT antibody, 
      SAR252067, was evaluated in healthy volunteers in a phase 1 study as a potential 
      treatment for diseases related to LIGHT-mediated mucosal inflammation. This 
      double-blind, randomized, placebo-controlled, sequential ascending single-dose, 
      single-center, 16-week study randomized 48 subjects to a single subcutaneous dose 
      of SAR252067 (40, 120, 300, 600, 900, or 1200 mg) or placebo. Safety assessments 
      included adverse events (AEs), injection-site reactions, and antidrug antibody 
      (ADA) titer. Pharmacokinetic end points were serum parameters of SAR252067 
      (C(max) , AUC(0-infinity) , t(max) , t(1/2z) ). Serum-soluble LIGHT concentrations were 
      also determined. Safety analyses included all 48 participants; pharmacokinetic 
      analyses included 36 subjects who received SAR252067. No serious AEs were 
      reported, and no dose-effect relationship was apparent. Injection-site reactions 
      were minimal. ADAs were not clinically relevant. SAR252067 exposure increased in 
      a near-dose-proportional manner, median t(max) ranged from 5.0 to 8.5 days, and 
      t(1/2z) ranged from 18.0 to 27.0 days. Serum-soluble LIGHT significantly 
      increased after SAR252067 administration with the 40-mg dose only. SAR252067 had 
      a good safety profile, was well tolerated in healthy humans, and displayed a 
      predictable pharmacokinetic profile.
CI  - (c) 2016, The American College of Clinical Pharmacology.
FAU - Zhang, Meng
AU  - Zhang M
AD  - Sanofi, Bridgewater, NJ, USA.
FAU - Perrin, Laurent
AU  - Perrin L
AD  - Biostatistics Department, Sanofi-Aventis Recherche Developpement, Montpellier, 
      France.
FAU - Pardo, Patricia
AU  - Pardo P
AD  - QPS Miami Research Associates, Miami, FL, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160928
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (SAR252067)
RN  - 0 (TNFSF14 protein, human)
RN  - 0 (Tumor Necrosis Factor Ligand Superfamily Member 14)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*administration & dosage/*pharmacokinetics
MH  - Antibodies, Monoclonal, Humanized
MH  - Area Under Curve
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Tumor Necrosis Factor Ligand Superfamily Member 14/*immunology
OTO - NOTNLM
OT  - LIGHT
OT  - SAR252067
OT  - inflammatory bowel disease
OT  - monoclonal antibody
OT  - pharmacokinetics
EDAT- 2016/08/23 06:00
MHDA- 2018/02/24 06:00
CRDT- 2016/08/23 06:00
PHST- 2016/03/22 00:00 [received]
PHST- 2016/08/17 00:00 [accepted]
PHST- 2016/08/23 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2016/08/23 06:00 [entrez]
AID - 10.1002/cpdd.295 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2017 May;6(3):292-301. doi: 10.1002/cpdd.295. Epub 2016 
      Sep 28.