PMID- 32268000
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20221207
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 13
IP  - 5
DP  - 2020 Sep
TI  - A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 Agonist 
      (RO7020531) in Chinese Healthy Volunteers.
PG  - 985-993
LID - 10.1111/cts.12791 [doi]
AB  - Toll-like receptor 7 (TLR7) agonists modulate broad spectrum immune activity and 
      are evaluated in the treatment of human diseases, including cancer and chronic 
      viral infection. RO7020531, an oral prodrug of a TLR7 agonist, is in clinical 
      development as part of a curative regimen against chronic hepatitis B. We report 
      the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of 
      RO7020531 in healthy Chinese volunteers following single and multiple ascending 
      doses (SAD and MAD). PK and PD samples were evaluated from four SAD cohorts and 3 
      MAD cohorts with 10 subjects each (8 active and 2 placebo). Safety and 
      tolerability were monitored throughout the study. A total of 155 adverse events 
      (AEs) were reported in 49 subjects. Fifty-one AEs in 18 subjects were assessed as 
      treatment-related. Most of the AEs were mild; nine subjects experienced moderate 
      AEs; there were no severe AEs. In two 150 mg MAD cohorts given every other day 
      (q.o.d.), 7 of 20 subjects experienced pyrexia and were discontinued due to 
      transient asymptomatic lymphopenia, which resolved 24-48 hours postdose. The PK 
      of the active metabolite, RO7011785, increased linearly with dose from 40 mg to 
      170 mg. There was no PK accumulation following q.o.d. dosing. The PK profile is 
      consistent with observations in white subjects in the global first-in-human 
      study. SADs and MADs of RO7020531 resulted in dose-dependent increases in TLR7 
      response markers at 100 mg or above. Flu-like symptoms were associated with 
      higher interferon-alpha levels. RO7020531 was safe and acceptably tolerated in 
      healthy Chinese volunteers with a multiple 150 mg q.o.d. dose regimen.
CI  - (c) 2020 Roche R&D China Ltd. Clinical and Translational Science published by Wiley 
      Periodicals Inc. on behalf of the American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Luk, Andrea
AU  - Luk A
AD  - Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Hong Kong 
      SAR, China.
FAU - Jiang, Qiudi
AU  - Jiang Q
AD  - Roche Innovation Center Shanghai, Shanghai, China.
FAU - Glavini, Katerina
AU  - Glavini K
AUID- ORCID: 0000-0001-6789-8781
AD  - Roche Innovation Center Basel, Basel, Switzerland.
FAU - Triyatni, Miriam
AU  - Triyatni M
AD  - Roche Innovation Center Basel, Basel, Switzerland.
FAU - Zhao, Na
AU  - Zhao N
AD  - Roche Pharma Development Shanghai, Shanghai, China.
FAU - Racek, Tomas
AU  - Racek T
AD  - Roche Innovation Center Basel, Basel, Switzerland.
FAU - Zhu, Yonghong
AU  - Zhu Y
AD  - Roche Innovation Center Shanghai, Shanghai, China.
FAU - Grippo, Joseph F
AU  - Grippo JF
AD  - Roche Innovation Center New York, New York, New York, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200514
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Antiviral Agents)
RN  - 0 (TLR7 protein, human)
RN  - 0 (Toll-Like Receptor 7)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Antiviral Agents/administration & dosage/*adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/etiology
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Hepatitis B, Chronic/drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Toll-Like Receptor 7/*agonists
MH  - Young Adult
PMC - PMC7485962
COIS- A.L. has no conflicts of interest regarding the contents of this article to 
      disclose; Q.J., K.G., M.T., N.Z., T.R., Y.Z., and J.F.G. are employees of F. 
      Hoffmann-La Roche and have no additional competing interests for this work.
EDAT- 2020/04/09 06:00
MHDA- 2021/08/24 06:00
PMCR- 2020/09/01
CRDT- 2020/04/09 06:00
PHST- 2020/01/03 00:00 [received]
PHST- 2020/03/08 00:00 [accepted]
PHST- 2020/04/09 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2020/04/09 06:00 [entrez]
PHST- 2020/09/01 00:00 [pmc-release]
AID - CTS12791 [pii]
AID - 10.1111/cts.12791 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2020 Sep;13(5):985-993. doi: 10.1111/cts.12791. Epub 2020 May 
      14.