PMID- 30581980
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220330
IS  - 2352-8737 (Electronic)
IS  - 2352-8737 (Linking)
VI  - 4
DP  - 2018
TI  - A randomized, single ascending dose study of intravenous BIIB092 in healthy 
      participants.
PG  - 746-755
LID - 10.1016/j.trci.2018.10.007 [doi]
AB  - INTRODUCTION: Extracellular tau is hypothesized to mediate the onset and 
      progression of tauopathies, including Alzheimer's disease, progressive 
      supranuclear palsy, and a subset of frontotemporal lobar degenerations. A 
      putative strategy for treating these disorders is to reduce extracellular tau 
      levels using tau-directed immunotherapy. The results of the first-in-human study 
      of BIIB092 (formerly BMS-986168/IPN007), a humanized monoclonal antibody that 
      binds to N-terminal tau, are reported here. This randomized, double-blind, single 
      ascending dose study evaluated the safety, tolerability, pharmacokinetics, 
      pharmacodynamics, and immunogenicity profile of BIIB092 after a single 
      intravenous infusion in healthy participants. METHODS: Sixty-five participants 
      were randomized to receive a single intravenous infusion of placebo or BIIB092 at 
      doses of 21, 70, 210, 700, 2100, or 4200 mg (or 700 or 2100 mg for Japanese 
      participants). Serial blood and cerebrospinal fluid samples were obtained for 
      assessment of pharmacokinetic parameters and unbound N-terminal tau suppression. 
      RESULTS: There were no deaths, serious adverse events (AEs), severe AEs, or 
      discontinuations due to an AE. The majority of AEs were mild. Serum BIIB092 
      concentrations increased in a dose-proportional manner and suppressed unbound 
      cerebrospinal fluid N-terminal tau by 67%-97% at 28 days after dose, with doses 
      of >/=210 mg producing persistent unbound N-terminal tau suppression over 12 weeks. 
      Levels of cerebrospinal fluid N-terminal tau suppression were similar for 
      Japanese and non-Japanese participants. DISCUSSION: BIIB092 was generally safe 
      and well tolerated after a single dose of up to 4200 mg, and up to 2100 mg in 
      Japanese participants. BIIB092 exhibited a dose-dependent increase in the extent 
      and duration of unbound N-terminal tau suppression.
FAU - Qureshi, Irfan A
AU  - Qureshi IA
AD  - Bristol-Myers Squibb, Lawrenceville, NJ, USA.
FAU - Tirucherai, Giridhar
AU  - Tirucherai G
AD  - Bristol-Myers Squibb, Lawrenceville, NJ, USA.
FAU - Ahlijanian, Michael K
AU  - Ahlijanian MK
AD  - Bristol-Myers Squibb, Lawrenceville, NJ, USA.
FAU - Kolaitis, Gerry
AU  - Kolaitis G
AD  - Bristol-Myers Squibb, Lawrenceville, NJ, USA.
FAU - Bechtold, Clifford
AU  - Bechtold C
AD  - Bristol-Myers Squibb, Lawrenceville, NJ, USA.
FAU - Grundman, Michael
AU  - Grundman M
AD  - Global R&D Partners, LLC, San Diego, CA, USA.
AD  - University of California San Diego, San Diego, CA, USA.
LA  - eng
PT  - Journal Article
DEP - 20181217
PL  - United States
TA  - Alzheimers Dement (N Y)
JT  - Alzheimer's & dementia (New York, N. Y.)
JID - 101650118
PMC - PMC6298197
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Phase 1
OT  - Progressive supranuclear palsy
OT  - Tau
OT  - Tauopathy
EDAT- 2018/12/26 06:00
MHDA- 2018/12/26 06:01
PMCR- 2018/12/17
CRDT- 2018/12/25 06:00
PHST- 2018/12/25 06:00 [entrez]
PHST- 2018/12/26 06:00 [pubmed]
PHST- 2018/12/26 06:01 [medline]
PHST- 2018/12/17 00:00 [pmc-release]
AID - S2352-8737(18)30069-6 [pii]
AID - 10.1016/j.trci.2018.10.007 [doi]
PST - epublish
SO  - Alzheimers Dement (N Y). 2018 Dec 17;4:746-755. doi: 10.1016/j.trci.2018.10.007. 
      eCollection 2018.