Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.
Adolescent
Adult
Aged
Antibodies, Monoclonal, Humanized
/ adverse effects
Autoimmune Diseases
/ drug therapy
Double-Blind Method
Female
Half-Life
Healthy Volunteers
Humans
Infusions, Intravenous
Interleukin-7 Receptor alpha Subunit
/ antagonists & inhibitors
Male
Middle Aged
Placebos
/ administration & dosage
T-Lymphocytes
/ drug effects
Young Adult
drug safety
immunology
monoclonal antibodies
pharmacodynamics
pharmacokinetics
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
12
01
2018
revised:
23
05
2018
accepted:
20
06
2018
pubmed:
31
8
2018
medline:
4
3
2020
entrez:
31
8
2018
Statut:
ppublish
Résumé
Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody. A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg GSK2618960 was well tolerated; there were no serious or significant adverse events. The observed half-life was 5 (±1) days (2.0 mg kg GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance.
Identifiants
pubmed: 30161291
doi: 10.1111/bcp.13748
pmc: PMC6339973
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
GSK2618960
0
IL7R protein, human
0
Interleukin-7 Receptor alpha Subunit
0
Placebos
0
Banques de données
ClinicalTrials.gov
['NCT02293161']
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
304-315Informations de copyright
© 2018 GlaxoSmithKline. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Arthritis Rheum. 2010 Apr;62(4):969-77
pubmed: 20131250
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12668-73
pubmed: 22733744
Cytometry B Clin Cytom. 2016 Mar;90(2):191-8
pubmed: 25914284
J Immunol. 1995 May 15;154(10):5093-102
pubmed: 7730615
Arthritis Rheum. 2010 Sep;62(9):2716-25
pubmed: 20499386
Arthritis Rheum. 2008 Nov;58(11):3430-5
pubmed: 18975340
J Immunol. 2012 Feb 15;188(4):1874-83
pubmed: 22262655
Semin Immunol. 2012 Jun;24(3):209-17
pubmed: 22551764
J Rheumatol. 1995 Aug;22(8):1581-5
pubmed: 7473488
Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1761-70
pubmed: 23610432
N Engl J Med. 2014 May 29;370(22):2102-10
pubmed: 24846652
Arthritis Rheum. 2013 Aug;65(8):2132-42
pubmed: 23666710
Br J Clin Pharmacol. 2019 Feb;85(2):304-315
pubmed: 30161291
J Exp Med. 1991 Apr 1;173(4):923-30
pubmed: 2007858
Rheumatology (Oxford). 2015 Nov;54(11):1941-3
pubmed: 26272073
Ann Rheum Dis. 2003 Feb;62(2):113-9
pubmed: 12525379
Nucleic Acids Res. 2018 Jan 4;46(D1):D1091-D1106
pubmed: 29149325
Br J Pharmacol. 2017 Dec;174 Suppl 1:S160-S194
pubmed: 29055033
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8732-7
pubmed: 11447288
Immunity. 2007 May;26(5):643-54
pubmed: 17521585
Sci Transl Med. 2011 Jul 27;3(93):93ra68
pubmed: 21795588
J Immunol. 1996 Feb 15;156(4):1333-8
pubmed: 8568231
Nat Rev Drug Discov. 2003 Jan;2(1):52-62
pubmed: 12509759
Ann Rheum Dis. 2012 Jun;71(6):1027-33
pubmed: 22312161
Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10961-6
pubmed: 20534450
Int Arch Allergy Immunol. 2014;163(3):185-92
pubmed: 24525665
AAPS J. 2012 Jun;14(2):296-302
pubmed: 22407289
Nat Immunol. 2000 Nov;1(5):426-32
pubmed: 11062503
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12674-9
pubmed: 22733769
N Engl J Med. 2007 Aug 30;357(9):851-62
pubmed: 17660530
J Exp Med. 2011 Aug 29;208(9):1875-87
pubmed: 21825017
Rheumatology (Oxford). 2012 Jun;51(6):996-1005
pubmed: 22302060
Nat Genet. 1998 Dec;20(4):394-7
pubmed: 9843216
PLoS One. 2014 Apr 16;9(4):e94756
pubmed: 24740301
J Clin Pharmacol. 2013 Feb;53(2):151-9
pubmed: 23436260
Clin Immunol Immunopathol. 1997 Apr;83(1):41-4
pubmed: 9073534
J Exp Med. 2006 Jul 10;203(7):1701-11
pubmed: 16818678
Nat Genet. 2007 Jul;39(7):857-64
pubmed: 17554260
Br J Pharmacol. 2017 Dec;174 Suppl 1:S225-S271
pubmed: 29055036
J Inflamm (Lond). 2012 Oct 12;9(1):39
pubmed: 23057802
Ann N Y Acad Sci. 2010 Jan;1183:13-24
pubmed: 20146705
J Autoimmun. 2013 Sep;45:40-8
pubmed: 23831438
Arthritis Rheum. 2005 Jun;52(6):1700-10
pubmed: 15934068