title: A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis.
abstract: 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.
authors.affiliation: Division of Dermatology, Georgetown University, Washington, District of Columbia, USA.
authors.forename: Catharine L
authors.initials: CL
authors.lastname: Kauffman
authors.forename: Nancy
authors.initials: N
authors.lastname: Aria
authors.forename: Eiko
authors.initials: E
authors.lastname: Toichi
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McCormick
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cooper
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Everitt
authors.forename: Bart
authors.initials: B
authors.lastname: Frederick
authors.forename: Yaowei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Martin A
authors.initials: MA
authors.lastname: Graham
authors.forename: Charles E
authors.initials: CE
authors.lastname: Pendley
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Mascelli
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D018664:Interleukin-12 / Q000276:immunology*; D053762:Interleukin-12 Subunit p40; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology* / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12