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Clinical Trial
. 2021 Mar;10(3):307-316.
doi: 10.1002/cpdd.887. Epub 2020 Dec 22.

Safety, Tolerability, and Pharmacokinetics of PF-06823859, an Anti-Interferon β Monoclonal Antibody: A Randomized, Phase I, Single- and Multiple-Ascending-Dose Study

Srividya Neelakantan  1 , Barry Oemar  1 , Kristen Johnson  2 , Natalie Rath  3 , Mikhail Salganik  1 , Gabe Berman  4 , Kathleen Pelletier  5 , Lori Cox  3 , Karen Page  1 , Dean Messing  1 , Sanela Tarabar  6
Affiliations
Clinical Trial

Safety, Tolerability, and Pharmacokinetics of PF-06823859, an Anti-Interferon β Monoclonal Antibody: A Randomized, Phase I, Single- and Multiple-Ascending-Dose Study

Srividya Neelakantan et al. Clin Pharmacol Drug Dev. 2021 Mar.

Abstract

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 β 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 β levels, such as dermatomyositis or systemic lupus erythematosus.

Keywords: PF-06823859; anti-interferon β monoclonal antibody; autoimmune disorders; pharmacokinetics; phase I; safety.

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References

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