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Anti‐IL21 receptor monoclonal antibody (ATR‐107): Safety, pharmacokinetics, and pharmacodynamic evaluation in healthy volunteers: A phase I, first‐in‐human study
Author(s) -
Hua Fei,
Comer Gail M.,
Stockert Lori,
Jin Bo,
Nowak John,
PleasicWilliams Susan,
Wunderlich David,
Cheng John,
Beebe Jean S.
Publication year - 2014
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.158
Subject(s) - pharmacokinetics , pharmacology , tolerability , pharmacodynamics , medicine , bioavailability , adverse effect , toxicity , monoclonal antibody , immunogenicity , antibody , placebo , immunology , pathology , alternative medicine
Safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ATR‐107, a fully human monoclonal anti‐IL‐21 receptor (IL‐21R) antibody, administered as ascending single doses, subcutaneously or intravenously, was evaluated in a placebo‐controlled, double‐blind trial in healthy subjects. The dose levels were 3–300 mg by SC and 30–120 mg by IV. The most important adverse events were hypersensitivity reactions occurring in three out of six subjects in 300 mg SC cohort and considered as dose limiting toxicity. More than 75% of the subjects who received ATR‐107 developed anti‐drug antibodies (ADAs), which had no discernible impact on PK or safety. The PK of ATR‐107 appeared to be dose ‐proportional. T1/2 was shorter than typical therapeutic antibodies. Bioavailability of ATR‐107 was about 30%. IL‐21R occupancy was measured in circulating B cells in the 60 and 120 mg IV cohort. The data indicated that single dose of ATR‐107 was able to maximally occupy IL‐21Rs through at least Day 42. Further escalation in the FIH study was halted partially due to the high rates of ADA formation. In conclusion, ATR‐107 had a prolonged PD effect measured by IL‐21R occupancy; was highly immunogenic after single dose administration and had PK properties with rapid clearance and low bioavailability.