title: Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  IL-23 is associated with plaque psoriasis susceptibility and pathogenesis. BI 655066 is a fully human IgG1 mAb specific for the IL-23 p19 subunit.
  
  
  OBJECTIVE
  This first-in-human proof-of-concept study evaluated the clinical and biological effects of BI 655066 in patients with moderate-to-severe plaque psoriasis.
  
  
  METHODS
  We performed a single-rising-dose, multicenter, randomized, double-blind, placebo-controlled, within-dose cohort phase I trial. Patients received 0.01, 0.05, 0.25, 1, 3, or 5 mg/kg BI 655066 intravenously, 0.25 or 1 mg/kg BI 655066 subcutaneously, or matched placebo. The primary objective was safety evaluation.
  
  
  RESULTS
  Thirty-nine patients received single-dose BI 655066 intravenously (n = 18) or subcutaneously (n = 13) or placebo (n = 8). Adverse events were reported with similar frequency in the BI 655066 and placebo groups. Four serious adverse events (not considered treatment related) were reported among BI 655066-treated patients. BI 655066 was associated with clinical improvement from week 2 and maintained for up to 66 weeks after treatment. At week 12, 75%, 90%, and 100% decreases in the Psoriasis Area and Severity Index were achieved by 87%, 58%, and 16% of BI 655066-treated patients (any dose), respectively, versus none receiving placebo. BI 655066 treatment resulted in reduced expression of lesional skin genes associated with IL-23/IL-17 signaling pathways and normalization of psoriatic lesion gene expression profiles to a profile approaching that of nonlesional skin. Significant correlation between treatment-associated molecular changes and psoriasis area and severity index improvement was observed (r = 0.73, P = 2 × 10(-6)).
  
  
  CONCLUSIONS
  BI 655066 was well tolerated and associated with rapid, substantial, and durable clinical improvement in patients with moderate-to-severe psoriasis, supporting a central role for IL-23 in psoriasis pathogenesis.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address: James.Krueger@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: UPMC Department of Dermatology, Pittsburgh, Pa.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Ferris
authors.affiliation: Baylor Research Institute, Dallas, Tex.
authors.forename: Alan
authors.initials: A
authors.lastname: Menter
authors.affiliation: Charité Research Organization, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wagner
authors.affiliation: Progressive Medical Research, Port Orange, Fla.
authors.forename: Alexander
authors.initials: A
authors.lastname: White
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Sudha
authors.initials: S
authors.lastname: Visvanathan
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Bojan
authors.initials: B
authors.lastname: Lalovic
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslanyan
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Elaine E L
authors.initials: EE
authors.lastname: Wang
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: David
authors.initials: D
authors.lastname: Hall
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Alan
authors.initials: A
authors.lastname: Solinger
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Padula
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Conn.
authors.forename: Paul
authors.initials: P
authors.lastname: Scholl
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011565:Psoriasis / Q000276:immunology / Q000628:therapy*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D020381:Interleukin-17; D053759:Interleukin-23; D010919:Placebos; C000601773:risankizumab
keywords: IL-23A; biomarkers; mAb; pharmacokinetics; psoriasis; randomized; single dose