PMID- 32667286
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20211006
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 25
IP  - 3
DP  - 2020
TI  - Safety, pharmacokinetics and pharmacodynamics of selgantolimod, an oral Toll-like 
      receptor 8 agonist: a Phase Ia study in healthy subjects.
PG  - 171-180
LID - 10.3851/IMP3363 [doi]
AB  - BACKGROUND: Selgantolimod is a novel oral, selective Toll-like receptor 8 (TLR8) 
      agonist in development for the treatment of chronic hepatitis B (CHB). TLR8 is an 
      endosomal innate immune receptor and a target for treatment of viral infections. 
      This first-in-human study investigated the safety, tolerability, pharmacokinetics 
      (PK) and pharmacodynamics (PD) of selgantolimod in healthy volunteers. METHODS: 
      Of 71 subjects enrolled, 59 received a single dose of selgantolimod (0.5, 1.5, 3 
      or 5 mg) or placebo, and 12 were evaluated for food effect. Safety, PK and PD 
      activity by induction of cytokines, chemokines and acute phase proteins were 
      assessed. PK/PD analyses were conducted. RESULTS: Single doses of 0.5-5 mg were 
      generally safe. No serious adverse events (AEs) or AEs leading to discontinuation 
      were reported, and most were Grade 1 in severity. Selgantolimod displayed rapid 
      absorption and dose-proportional PK and PD activity. Food had minimal effect on 
      PK but resulted in diminished PD activity. In PK/PD analyses, near-saturation of 
      induction for most evaluated biomarkers occurred at the 5-mg dose. CONCLUSIONS: 
      Single doses of up to 5 mg selgantolimod were safe and induced dose-dependent PD 
      responses. These data support evaluation of selgantolimod in combination with 
      other agents in future clinical studies of CHB. Australian New Zealand Clinical 
      Trials Registration: ACTRN12616001646437.
FAU - Reyes, Maribel
AU  - Reyes M
AD  - Clinical Pharmacology, Gilead Sciences, Foster City, CA, USA.
FAU - Lutz, Justin D
AU  - Lutz JD
AD  - Clinical Pharmacology, Gilead Sciences, Foster City, CA, USA.
FAU - Lau, Audrey H
AU  - Lau AH
AD  - Clinical Research, Gilead Sciences, Foster City, CA, USA.
FAU - Gaggar, Anuj
AU  - Gaggar A
AD  - Clinical Research, Gilead Sciences, Foster City, CA, USA.
FAU - Grant, Ethan P
AU  - Grant EP
AD  - Biology, Gilead Sciences, Foster City, CA, USA.
FAU - Joshi, Adarsh
AU  - Joshi A
AD  - Biostatistics, Gilead Sciences, Foster City, CA, USA.
FAU - Mackman, Richard L
AU  - Mackman RL
AD  - Medicinal Chemistry, Gilead Sciences, Foster City, CA, USA.
FAU - Ling, John
AU  - Ling J
AD  - Bioanalytical Chemistry, Gilead Sciences, Foster City, CA, USA.
FAU - Tan, Susanna K
AU  - Tan SK
AD  - Clinical Research, Gilead Sciences, Foster City, CA, USA.
FAU - Ayithan, Natarajan
AU  - Ayithan N
AD  - Institute of Human Virology, University of Maryland, Baltimore, MD, USA.
FAU - Daffis, Stephane
AU  - Daffis S
AD  - Biology, Gilead Sciences, Foster City, CA, USA.
FAU - Woo, Jacky
AU  - Woo J
AD  - Biology, Gilead Sciences, Foster City, CA, USA.
FAU - Wu, Peiwen
AU  - Wu P
AD  - Biostatistics, Gilead Sciences, Foster City, CA, USA.
FAU - Lam, Tina
AU  - Lam T
AD  - Clinical Operations, Gilead Sciences, Foster City, CA, USA.
FAU - Fletcher, Simon P
AU  - Fletcher SP
AD  - Biology, Gilead Sciences, Foster City, CA, USA.
FAU - Kottilil, Shyamasundaran
AU  - Kottilil S
AD  - Institute of Human Virology, University of Maryland, Baltimore, MD, USA.
FAU - Poonia, Bhawna
AU  - Poonia B
AD  - Institute of Human Virology, University of Maryland, Baltimore, MD, USA.
FAU - Gane, Edward J
AU  - Gane EJ
AD  - Auckland Clinical Studies, Auckland, New Zealand.
FAU - Mathias, Anita
AU  - Mathias A
AD  - Clinical Pharmacology, Gilead Sciences, Foster City, CA, USA.
FAU - German, Polina
AU  - German P
AD  - Clinical Pharmacology, Gilead Sciences, Foster City, CA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Antiviral Agents)
RN  - 0 (Chemokines)
RN  - 0 (Hexanols)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Pyrimidines)
RN  - 0 (TLR8 protein, human)
RN  - 0 (Toll-Like Receptor 8)
RN  - 187348-17-0 (Interleukin-12)
RN  - RM4GJT3SMQ (selgantolimod)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Antiviral Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Chemokines/blood
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hepatitis B, Chronic/drug therapy
MH  - Hexanols/administration & dosage/adverse effects/pharmacokinetics/*pharmacology
MH  - Humans
MH  - Interleukin 1 Receptor Antagonist Protein/blood
MH  - Interleukin-12/blood
MH  - Male
MH  - Pyrimidines/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Toll-Like Receptor 8/*agonists
MH  - Young Adult
EDAT- 2020/07/16 06:00
MHDA- 2021/10/07 06:00
CRDT- 2020/07/16 06:00
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2020/07/16 06:00 [entrez]
AID - 10.3851/IMP3363 [doi]
PST - ppublish
SO  - Antivir Ther. 2020;25(3):171-180. doi: 10.3851/IMP3363.