title: Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and safety of ixekizumab following subcutaneous administration using a prefilled syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis (UNCOVER-A).
abstract: BACKGROUND
  The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis patients when administered via prefilled syringe (PFS).
  
  
  OBJECTIVE
  To evaluate the effect of two drug delivery devices on the pharmacokinetics (PK) of ixekizumab as well as efficacy and safety with both devices.
  
  
  METHODS
  In the first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis patients were randomized to ixekizumab delivery via PFS or autoinjector device. Randomization was stratified by weight (<80 kg, 80-100 kg, >100 kg), injection assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160-mg initial dose at week 0, patients received subcutaneous 80-mg ixekizumab as a single injection every 2 weeks for 12 weeks. Blood samples were collected following the initial 160-mg dose on days 2, 4, 7, 10 and 14 for PK analysis. Primary PK parameters were maximum concentration (Cmax) and area under the curve (AUC0-tlast) where tlastis the time of last sample (14 days ± 24 h). Efficacy was assessed by percent improvement on the Psoriasis Area and Severity Index (PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory data were used to evaluate safety.
  
  
  RESULTS
  Of 204 randomized patients, 192 were included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector showed similar geometric mean Cmax(90% CI) [15.0 μg/mL (13.9-16.1) vs. 14.8 μg/mL (13.8-15.9)] and geometric mean AUC0-tlast(90% CI) [157 μg × day/mL (147-168) vs. 154 μg × day/mL (144-165)]. When comparing Cmaxand AUC0-tlastof the autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean percent PASI improvement (via modified baseline observation carried forward) was similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety results that were consistent with the known safety profile of ixekizumab.
  
  
  CONCLUSIONS
  The PK, efficacy and safety of ixekizumab administered subcutaneously by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191 https://clinicaltrials.gov/ct2/show/NCT01777191.
authors: Department of Dermatology, University of Utah, Salt Lake City, UT, USA.
authors: K
authors: K
authors: Callis Duffin
authors: Psoriasis Treatment Center of Central New Jersey, Windsor, NJ, USA.
authors: J
authors: J
authors: Bagel
authors: Altman Dermatology Associates, Arlington Heights, IL, USA.
authors: M
authors: M
authors: Bukhalo
authors: Lilly-NUS Centre for Clinical Pharmacology, Singapore City, Singapore.
authors: I J
authors: IJ
authors: Mercado Clement
authors: Lilly-NUS Centre for Clinical Pharmacology, Singapore City, Singapore.
authors: S L
authors: SL
authors: Choi
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: F
authors: F
authors: Zhao
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: A
authors: A
authors: Gill
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: B
authors: B
authors: Pangallo
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: C
authors: C
authors: Shuler
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: L
authors: L
authors: Mallbris
authors: Eli Lilly and Company, Windlesham, UK.
authors: K
authors: K
authors: Jackson
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C549079:ixekizumab