PMID- 29952004
OWN - NLM
STAT- MEDLINE
DCOM- 20191015
LR  - 20231213
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 105
IP  - 1
DP  - 2019 Jan
TI  - Randomized Phase I Healthy Volunteer Study of UTTR1147A (IL-22Fc): A Potential 
      Therapy for Epithelial Injury.
PG  - 177-189
LID - 10.1002/cpt.1164 [doi]
AB  - Most treatments for epithelial injury target hematopoietic mechanisms, possibly 
      causing immunosuppression. Interleukin (IL)-22 promotes tissue regeneration, 
      acting directly on epithelial cells. UTTR1147A, a human IL-22Fc (immunoglobulin G 
      (IgG)4) fusion protein, activates IL-22 signaling. This phase I 
      placebo-controlled trial of single, ascending, i.v. (1-120 mug/kg) and s.c 
      (3-120 mug/kg) doses of UTTR1147A analyzed its effects on safety, tolerability, 
      pharmacokinetics, and pharmacodynamic biomarkers in healthy volunteers. Most 
      adverse events (AEs) were mild or moderate. The maximum tolerated i.v. dose in 
      healthy volunteers was 90 mug/kg. Predominant AEs were dose-dependent reversible 
      skin effects consistent with IL-22 pharmacology. UTTR1147A exposure increased 
      approximately dose-proportionally, with a half-life of ~1 week. IL-22 biomarkers 
      (regenerating islet protein 3A (REG3A), serum amyloid A (SAA), and C-reactive 
      protein (CRP)) increased dose-dependently. Neither inflammatory symptoms and 
      signs nor cytokines increased with CRP elevations. UTTR1147A demonstrated 
      acceptable safety, pharmacokinetics, and IL-22R engagement, supporting further 
      clinical development.
CI  - (c) 2018 The American Society for Clinical Pharmacology and Therapeutics.
FAU - Rothenberg, Michael E
AU  - Rothenberg ME
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Wang, Yehong
AU  - Wang Y
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Lekkerkerker, Annemarie
AU  - Lekkerkerker A
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Danilenko, Dimitry M
AU  - Danilenko DM
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Maciuca, Romeo
AU  - Maciuca R
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Erickson, Rich
AU  - Erickson R
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Herman, Ann
AU  - Herman A
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Stefanich, Eric
AU  - Stefanich E
AD  - Genentech, Inc., South San Francisco, California,, USA.
FAU - Lu, Timothy T
AU  - Lu TT
AD  - Genentech, Inc., South San Francisco, California,, USA.
LA  - eng
SI  - EudraCT/2014-002252-10
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180812
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukins)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/*drug effects/metabolism/pathology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunoglobulin G/*administration & dosage/metabolism
MH  - Interleukins/*administration & dosage/metabolism
MH  - Male
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/*administration & dosage/metabolism
MH  - Single-Blind Method
MH  - Young Adult
MH  - Interleukin-22
EDAT- 2018/06/29 06:00
MHDA- 2019/10/16 06:00
CRDT- 2018/06/29 06:00
PHST- 2018/05/08 00:00 [received]
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/06/29 06:00 [pubmed]
PHST- 2019/10/16 06:00 [medline]
PHST- 2018/06/29 06:00 [entrez]
AID - 10.1002/cpt.1164 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2019 Jan;105(1):177-189. doi: 10.1002/cpt.1164. Epub 2018 
      Aug 12.