title: A phase 1 study investigating DX-2930 in healthy subjects.
abstract: BACKGROUND
  DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein under investigation for long-term prophylaxis of hereditary angioedema.
  
  
  OBJECTIVE
  To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of DX-2930 in healthy subjects.
  
  
  METHODS
  A single-center, double-blinded study was performed in 32 healthy subjects randomized 3:1 to receive a single subcutaneous administration of DX-2930 or placebo within 1 of 4 sequential, ascending dose cohorts (n = 8 each): 0.1, 0.3, 1.0, or 3.0 mg/kg.
  
  
  RESULTS
  No dose-limiting toxicity was observed. Headache was the most commonly reported treatment emergent adverse event (AE), occurring at a rate of 25% in the DX-2930- and placebo-treated groups; none were severe and all resolved. There were no serious AEs, discontinuations owing to an AE, or deaths. Two subjects had a severe AE reported as related to treatment by the blinded investigator; the 2 AEs were asymptomatic creatinine phosphokinase elevations of 902 U/L in 1 subject receiving 0.1 mg/kg DX-2930 and 1,967 U/L in 1 subject receiving placebo. For the 0.1-, 0.3-, 1.0-, and 3.0-mg/kg dose groups, respectively, mean maximum plasma concentrations were 0.6, 1.4, 5.6, and 14.5 μg/mL and mean elimination half-lives were 20.6, 16.8, 17.6, and 21.2 days. Exploratory biomarker assays, involving ex vivo activation of the kallikrein pathway, showed dose- and time-dependent inhibition of plasma kallikrein, with evidence of sustained bioactivity consistent with the pharmacokinetics profile.
  
  
  CONCLUSIONS
  A single administration of DX-2930 in healthy subjects up to doses of 3.0 mg/kg was well tolerated without dose-limiting toxicity. Pharmacokinetic and pharmacodynamic data provide evidence for a long-acting biological effect relevant to long-term prophylaxis for hereditary angioedema with C1-inhibitor deficiency.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01923207.
authors: Dyax Corp, Burlington, Massachusetts. Electronic address: ychyung@dyax.com.
authors: Yung
authors: Y
authors: Chyung
authors: Vince & Associates Clinical Research, Overland Park, Kansas.
authors: Bradley
authors: B
authors: Vince
authors: Dyax Corp, Burlington, Massachusetts.
authors: Ryan
authors: R
authors: Iarrobino
authors: Dyax Corp, Burlington, Massachusetts.
authors: Dan
authors: D
authors: Sexton
authors: Dyax Corp, Burlington, Massachusetts.
authors: Jon
authors: J
authors: Kenniston
authors: Dyax Corp, Burlington, Massachusetts.
authors: Ryan
authors: R
authors: Faucette
authors: Dyax Corp, Burlington, Massachusetts.
authors: Chris
authors: C
authors: TenHoor
authors: Dyax Corp, Burlington, Massachusetts.
authors: Leslie E
authors: LE
authors: Stolz
authors: Dyax Corp, Burlington, Massachusetts.
authors: Chris
authors: C
authors: Stevens
authors: Dyax Corp, Burlington, Massachusetts.
authors: Joseph
authors: J
authors: Biedenkapp
authors: Dyax Corp, Burlington, Massachusetts.
authors: Burt
authors: B
authors: Adelman
mesh_terms: D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000596550:lanadelumab; D007610:Kallikreins