title: First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  The objective of this paper is to investigate the safety, pharmacokinetics (PK) and immunogenicity of CDP7657, a PEGylated anti-CD40L antibody fragment, in healthy individuals and patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  This randomized, double-blind, single-dose, dose-escalation phase I study consisted of two parts. In part 1, 28 healthy individuals received CDP7657 IV (0.004-5 mg/kg) or placebo. In part 2, 17 patients with SLE received CDP7657 IV (5-60 mg/kg) or placebo. The CDP7657:placebo ratio was 3:1.
  
  
  RESULTS
  Adverse events (AEs) were reported by 76% of healthy individuals and 100% of patients with SLE treated with CDP7657; most were mild or moderate in intensity. Two healthy individuals reported serious AEs (SAEs), one of which was considered treatment related (infusion-related reaction; 5 mg/kg cohort). One patient with SLE (60 mg/kg cohort) experienced three SAEs, one of which was considered treatment related (herpes zoster infection). No thromboembolic events were reported. CPD7657 exposure increased in a dose-proportional manner. Low anti-CDP7657 antibody titres were detected in the majority of CDP7657-treated participants with no apparent impact on the PK of CDP7657.
  
  
  CONCLUSIONS
  Single doses of CDP7657 showed predictable PK in healthy individuals and patients with SLE and were well tolerated, with no safety signals of concern. These findings support further investigation of CDP7657 as a therapy for SLE.
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: A
authors.initials: A
authors.lastname: Tocoian
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: P
authors.initials: P
authors.lastname: Buchan
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: H
authors.initials: H
authors.lastname: Kirby
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: J
authors.initials: J
authors.lastname: Soranson
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: M
authors.initials: M
authors.lastname: Zamacona
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: R
authors.initials: R
authors.lastname: Walley
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mitchell
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: E
authors.initials: E
authors.lastname: Esfandiari
authors.affiliation: Charité Research Organisation GmbH, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wagner
authors.affiliation: UCB Pharma, Slough, UK Ruth.Oliver@ucb.com.
authors.forename: R
authors.initials: R
authors.lastname: Oliver
mesh_terms: D000328:Adult; D023201:CD40 Ligand / Q000037:antagonists & inhibitors* / Q000276:immunology; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000009:adverse effects*; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; C000607972:dapirolizumab pegol; D023201:CD40 Ligand; D011092:Polyethylene Glycols
keywords: CDP7657; anti-CD40L; lupus; systemic lupus erythematosus