PMID- 33352008
OWN - NLM
STAT- MEDLINE
DCOM- 20211221
LR  - 20211221
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 10
IP  - 3
DP  - 2021 Mar
TI  - Safety, Tolerability, and Pharmacokinetics of PF-06823859, an Anti-Interferon beta 
      Monoclonal Antibody: A Randomized, Phase I, Single- and Multiple-Ascending-Dose 
      Study.
PG  - 307-316
LID - 10.1002/cpdd.887 [doi]
AB  - This double-blind, randomized, placebo-controlled, dose-ascending, first-in-human 
      study (NCT02766621) assessed the safety, tolerability, and pharmacokinetics (PK) 
      of PF-06823859, an anti-interferon beta monoclonal antibody. Healthy subjects were 
      randomized to single ascending doses (SADs) of intravenous PF-06823859 30, 100, 
      300, 900, or 2000 mg or placebo; to multiple ascending doses (MADs) of 
      subcutaneous PF-06823859 100 or 300 mg or placebo (once every 2 weeks for a total 
      of 3 doses); or to MAD of intravenous PF-06823859 600 mg or placebo (once every 3 
      weeks or once every 4 weeks for a total of 2 doses). The incidence, severity, and 
      causal relationship of adverse events (AEs) were assessed, along with 
      immunogenicity and PK. In total, 62 subjects were randomized to treatment (SAD, 
      n = 35; MAD, n = 27). There were 76 treatment-emergent all-causality AEs in the 
      SAD (PF-06823859: n = 25; placebo: n = 4) and MAD (PF-06823859: n = 40; placebo: 
      n = 7) cohorts. In the SAD cohorts, all treatment-emergent all-causality AEs were 
      mild in severity; 4 AEs of moderate severity were identified in the MAD cohorts. 
      No dose-limiting AEs, serious AEs, treatment-related discontinuations, dose 
      reductions, or deaths occurred. PF-06823859 exposure increased 
      dose-proportionally, with half-life values ranging between 23 and 35 days. The 
      estimated subcutaneous bioavailability was 43% to 44%. Immunogenicity incidence 
      rates were low (antidrug antibodies, 12.5%; neutralizing antibodies, 2.1%). No 
      immunogenically related clinical responses of concern were observed. In 
      conclusion, PF-06823859 demonstrated an acceptable safety, tolerability, and PK 
      profile that supports clinical development for treating disorders associated with 
      increased interferon beta levels, such as dermatomyositis or systemic lupus 
      erythematosus.
CI  - (c) 2020, The American College of Clinical Pharmacology.
FAU - Neelakantan, Srividya
AU  - Neelakantan S
AD  - Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
FAU - Oemar, Barry
AU  - Oemar B
AD  - Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
FAU - Johnson, Kristen
AU  - Johnson K
AD  - Center for Therapeutic Innovation, Pfizer Inc, New York, New York, USA.
FAU - Rath, Natalie
AU  - Rath N
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Salganik, Mikhail
AU  - Salganik M
AD  - Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
FAU - Berman, Gabe
AU  - Berman G
AD  - Pfizer Inc, San Diego, California, USA.
FAU - Pelletier, Kathleen
AU  - Pelletier K
AD  - Pfizer Inc, Groton, Connecticut, USA.
FAU - Cox, Lori
AU  - Cox L
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Page, Karen
AU  - Page K
AD  - Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
FAU - Messing, Dean
AU  - Messing D
AD  - Worldwide Research and Development, Pfizer Inc, Cambridge, Massachusetts, USA.
FAU - Tarabar, Sanela
AU  - Tarabar S
AD  - Pfizer Clinical Research Unit, New Haven, Connecticut, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02766621
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20201222
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Placebos)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Administration, Intravenous
MH  - Adult
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects/*pharmacokinetics
MH  - Antibodies, Neutralizing/drug effects
MH  - Autoimmune Diseases/*drug therapy/immunology
MH  - Biological Availability
MH  - Case-Control Studies
MH  - Double-Blind Method
MH  - Drug Tolerance
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Immunity/*drug effects
MH  - Injections, Subcutaneous
MH  - Interferon-beta/*antagonists & inhibitors/blood/metabolism
MH  - Male
MH  - Middle Aged
MH  - Pharmacokinetics
MH  - Placebos/administration & dosage
MH  - Safety
OTO - NOTNLM
OT  - PF-06823859
OT  - anti-interferon beta monoclonal antibody
OT  - autoimmune disorders
OT  - pharmacokinetics
OT  - phase I
OT  - safety
EDAT- 2020/12/23 06:00
MHDA- 2021/12/22 06:00
CRDT- 2020/12/22 17:15
PHST- 2020/03/12 00:00 [received]
PHST- 2020/10/12 00:00 [accepted]
PHST- 2020/12/23 06:00 [pubmed]
PHST- 2021/12/22 06:00 [medline]
PHST- 2020/12/22 17:15 [entrez]
AID - 10.1002/cpdd.887 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2021 Mar;10(3):307-316. doi: 10.1002/cpdd.887. Epub 2020 
      Dec 22.