Guselkumab pharmacokinetics and immunogenicity in pediatric psoriasis: Phase 3 PROTOSTAR study

Summary: Abstract Body: PROTOSTAR evaluated guselkumab (GUS), a selective IL-23p19 subunit inhibitor, in pediatric study participants (pts; ≥6-<18y) with moderate-to-severe plaque psoriasis (PsO; ClinicalTrials.gov: NCT03451851). GUS pharmacokinetics (PK) and immunogenicity were assessed to determine whether PK exposure achieved with pediatric weight-based (WB) dosing was comparable with that established for the approved adult dose regimen. In prior studies, mean steady-state (SS) trough serum GUS concentration in adult PsO pts was approximately 1.2μg/mL. In Part 1 (Weeks [W]0-16), pts were randomized to GUS, placebo, or an open-label etanercept reference arm. At W16 (primary endpoint), Part 1 pts entered GUS withdrawal/retreatment, GUS continuation, or crossover to GUS study periods (W16-52). Part 2 evaluated continuous, open-label GUS treatment in a single arm of pts ≥12y (W0-52). Pts received a WB GUS dose of 1.3mg/kg for pts <70 kg or 100mg for pts ≥70 kg. PK and immunogenicity endpoints (Parts 1&2) included serum GUS concentrations through W16 and W44, and proportions of pts with antibodies (Ab) to GUS, neutralizing Ab (NAb), and Ab titers. In Parts 1&2, 41 and 28 pts received GUS, respectively. In Part 1, mean serum GUS concentrations at W16 were slightly lower in pts aged ≥6-<12y (2.83μg/mL) vs ≥12-<18y (3.61μg/mL); however, ranges largely overlapped. Similar W16 concentrations were observed for the <70 kg and ≥70 kg groups (3.53 and 3.19μg/mL, respectively). In Parts 1&2, SS trough serum GUS concentrations were achieved by W20 and maintained through W44. In Part 2, W20 mean SS trough serum GUS concentrations were 1.50 and 1.54μg/mL for the <70 kg and ≥70 kg groups, respectively. Among 114 GUS-treated pts with available samples through W44, 21 (18.4%) tested positive for Ab to GUS; none had NAb. Ab titers were generally low (80.0% had titers ≤1:160). The development and titers of Ab to GUS did not impact GUS PK or clinical response. The observed PK for GUS in pediatric PsO pts receiving WB dosing was generally comparable with PK in adults with PsO. Vikash Sinha¹, Herta Crauwels¹, Obinna Obianom¹, Bart van Hartingsveldt¹, Meg Jett¹, Jingzhi Jiang¹, An Vermeulen¹ 1. Johnson and Johnson, Spring House, PA, United States. Clinical Research: Interventional Research