safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α results of a phase i randomized, placebo-controlled trialpateclizumab安全、药物动力学和生物活动,一种新型单克隆抗体针对淋巴毒素α相的结果我随机、安慰剂对照试验.pdfVIP

Emu et al. Arthritis Research Therapy 2012, 14:R6 /content/14/1/R6 RESEARCH ARTICLE Open Access Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin a: results of a phase I randomized, placebo-controlled trial 1 1 1 1 2 1 Brinda Emu , Diana Luca , Carolyn Offutt , Jane L Grogan , Bernadette Rojkovich , Marna B Williams , 1 1 3 1* Meina T Tang , Jim Xiao , June H Lee and John C Davis Abstract Introduction: Pateclizumab (MLTA3698A) is a humanized mAb against lymphotoxin a (LTa), a transiently expressed cytokine on activated B and T cells (Th1, Th17), which are implicated in rheumatoid arthritis (RA) pathogenesis. This study was conducted to assess the safety, tolerability, NOTE: For clarity and per AMA/S-W Style, please restore the use of Oxford/serial commas (ie: David likes vanilla, strawberry, and chocolate ice cream) throughout. and biologic activity of single and multiple doses of intravenous (IV) or subcutaneous (SC) pateclizumab in RA patients. Methods: The single ascending dose (SAD) phase in patients with stable RA consisted of six cohorts (4:1 active: placebo at 0.3 mg/kg IV, 1.0 mg/kg IV, 1.0 mg/kg SC, 3.0 mg/kg IV, 3.0 mg/kg SC, and 5.0 mg/kg IV; n = 5/cohort). In the multiple ascending dose (MAD) phase, patients with prespecified RA disease activity received three doses of pateclizumab or placebo (4:1) every 2 weeks (1.0 mg/kg SC, n = 10; 3.0 mg/kg SC, n = 20; or 5.0 mg/kg IV, n = 5). Safety and tolerability were assessed throughout, and clinical activity was determined after three doses (Week 6). Results: We observed no serious adverse events (AEs) or dose-l