A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants
© 2024 AstraZeneca and The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology..
Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged 18-45 years with a body mass index 19-24 kg/m2 were enrolled. In total, 36 participants across 2 cohorts of 18 participants were randomized 2:1 to receive a single subcutaneous dose of tozorakimab (300 mg [2 mL] or 600 mg [4 mL]) or matching placebo (2 or 4 mL). Tozorakimab showed dose-dependent serum PK concentrations with an approximate monophasic distribution in serum over time and a maximum observed peak concentration of 20.1 and 33.7 μg/mL in the 300- and 600-mg cohorts, respectively. No treatment-emergent anti-drug antibodies for tozorakimab were observed in any of the participants. There were no clinically relevant trends in the occurrence of TEAEs across the treatment groups. There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Clinical pharmacology in drug development - (2024) vom: 25. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yunfei [VerfasserIn] |
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Date Revised 25.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/cpdd.1391 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370130537 |
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| 245 | 1 | 2 | |a A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants |
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| 520 | |a Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab. Safety outcomes included treatment-emergent adverse events (TEAEs) and clinical laboratory, electrocardiogram, and vital sign parameters. Healthy, non-smoking, male, and female Chinese participants aged 18-45 years with a body mass index 19-24 kg/m2 were enrolled. In total, 36 participants across 2 cohorts of 18 participants were randomized 2:1 to receive a single subcutaneous dose of tozorakimab (300 mg [2 mL] or 600 mg [4 mL]) or matching placebo (2 or 4 mL). Tozorakimab showed dose-dependent serum PK concentrations with an approximate monophasic distribution in serum over time and a maximum observed peak concentration of 20.1 and 33.7 μg/mL in the 300- and 600-mg cohorts, respectively. No treatment-emergent anti-drug antibodies for tozorakimab were observed in any of the participants. There were no clinically relevant trends in the occurrence of TEAEs across the treatment groups. There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study | ||
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| 700 | 1 | |a Pandya, Hitesh |e verfasserin |4 aut | |
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| 700 | 1 | |a Reid, Fred |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez, Eulalia |e verfasserin |4 aut | |
| 700 | 1 | |a Sadiq, Muhammad Waqas |e verfasserin |4 aut | |
| 700 | 1 | |a Moate, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Alejhandra |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiao-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Kell, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Junjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Guanlin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Xiaoyun |e verfasserin |4 aut | |
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