Pharmacokinetics, Safety, and Tolerability of Single‐Dose Dazukibart in Healthy Adults in China and Japan: Results From 2 Randomized, Double‐Blind, Phase 1 Studies
Dazukibart is a humanized monoclonal antibody selectively targeting interferon-β. The pharmacokinetics (PK), safety, tolerability, and immunogenicity of dazukibart were evaluated in 2 double-blind, randomized, placebo-controlled, single-dose, Phase 1 studies in healthy adults in China (Study 1: N = 18; dazukibart 900 mg = 15; placebo = 3) and Japan (Study 2: N = 12; Cohort 1: dazukibart 300 mg = 5, placebo = 1; and Cohort 2: dazukibart 900 mg = 5, placebo = 1). PK parameters were assessed after dosing in Study 1 and Study 2, and no significant differences were observed between PK findings among participants in both studies. A biphasic decline in dazukibart serum concentrations was observed in both studies. Exposures increased dose proportionally in Study 2. Body weight, but not race, was identified as an independent covariate of exposure using population PK modeling (including data from a Phase 1 US study [NCT02766621]). No deaths/discontinuations or serious/severe adverse events were observed, mostly mild adverse events were reported. No participants in Study 1 were antidrug antibody positive; 20.0% in Study 2 were positive for treatment-induced antidrug antibodies and neutralizing antibodies. PK parameters and immunogenicity rates were consistent with the US study, and no new safety signals were identified.
Authors
- Kenji Takazawa (ORCID: https://orcid.org/0000-0002-6840-9086)
- Shui‐yi Hu (ORCID: https://orcid.org/0000-0003-2036-0866)
- Naihan Chen (ORCID: https://orcid.org/0000-0002-7145-0776)
- Myron Chu (ORCID: https://orcid.org/0000-0001-5763-5603)
- Junichi Tabira
- John P. Prybylski (ORCID: https://orcid.org/0000-0001-5802-0539)
- Hiroki Yoshimatsu
- Yamato Sano (ORCID: https://orcid.org/0000-0002-5512-2190)
- Xin Luo (ORCID: https://orcid.org/0000-0002-1348-5305)
- Haiyan Li (ORCID: https://orcid.org/0000-0002-8286-2813)
- Xiaohong Wang (ORCID: https://orcid.org/0000-0001-8628-243X)
Institutions
- Pfizer (United States) (US)
- Peking University (CN)
- Peking University Third Hospital (CN)
- Pfizer (China) (CN)
- Pfizer (Japan) (JP)
Publication Details
- Journal
- Clinical Pharmacology in Drug Development
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1002/cpdd.1522
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pfizer