A Phase I Study Evaluating the Safety, Pharmacokinetics, and Clinical Response of a Human IL-12 p40 Antibody in Subjects with Plaque Psoriasis
Autor: | Bart Frederick, Daniel E. Everitt, Mary Ann Mascelli, Yaowei Zhu, Charles Pendley, Alice B. Gottlieb, Martin A. Graham, Kevin D. Cooper, Nancy Aria, Thomas S. McCormick, Eiko Toichi, Catharine L. Kauffman |
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Rok vydání: | 2004 |
Předmět: |
Adult
Male medicine.medical_specialty anti-IL-12p40 Dermatology Severity of Illness Index Biochemistry Gastroenterology Pharmacokinetics Psoriasis Area and Severity Index Internal medicine Psoriasis Severity of illness medicine Humans Adverse effect Molecular Biology Body surface area interleukin-23 Interleukin-12 Subunit p40 business.industry PASI Immunoglobulins Intravenous Cell Biology Middle Aged medicine.disease Interleukin-12 Clinical trial Protein Subunits Treatment Outcome Immunology Toxicity Female business |
Zdroj: | Journal of Investigative Dermatology. 123:1037-1044 |
ISSN: | 0022-202X |
Popis: | The potential therapeutic activity of a human monoclonal antibody to the human interleukin-12 p40 subunit (anti-IL-12p40) has been established both in vitro and in vivo, warranting a first-in-human investigation in psoriasis. This phase I, first-in-human, non-randomized, open-label study evaluated the short-term safety, pharmacokinetics, and clinical response of single, ascending, intravenous (IV) doses of anti-IL-12p40 in subjects with moderate-to-severe psoriasis vulgaris. Eighteen subjects with at least 3% body surface area involvement were enrolled in four dose groups (0.1, 0.3, 1.0, and 5.0 mg per kg). Safety, pharmacokinetics, and clinical response (e.g., Psoriasis Area and Severity Index (PASI)) were monitored at baseline and at specific time points over a 16-wk follow-up period. Anti-IL-12p40 was generally well tolerated. No related serious adverse events or infusion reactions were reported, and most adverse events were mild. IV anti-IL-12p40 yielded linear pharmacokinetics, with a mean terminal half-life of approximately 24 d. Dose-dependent associations with both the rate and extent of clinical response were observed across the four dose groups. Twelve of 18 subjects (67%) achieved at least a 75% improvement in PASI between 8 and 16 wk after study agent administration. Significant and sustained concentration-dependent improvements in psoriatic lesions were observed in most subjects. |
Databáze: | OpenAIRE |
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