Abstract: SA-PO0681
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARGX-121 in Healthy Adult Participants: Results from the Phase 1 First-in-Human Study
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - Other
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
- Dosne, Anne-Gaelle, argenx, Ghent, Belgium
- Meizlik, Paige, argenx, Ghent, Belgium
- Ordonez, Jhonny, argenx, Ghent, Belgium
- Leng, Xinghong, argenx, Ghent, Belgium
- De Cauwer, Lode, argenx, Ghent, Belgium
- Van Coillie, Samya, argenx, Ghent, Belgium
- Voet, Sofie, argenx, Ghent, Belgium
- Bolca, Selin, argenx, Ghent, Belgium
- Silence, Karen, argenx, Ghent, Belgium
Background
ARGX-121, a one-armed monoclonal immunoglobulin (Ig) G1 antibody that targets IgA, is engineered to diminish effector functions and increase binding affinity to the neonatal Fc receptor (FcRn). Through pH-dependent IgA binding and enhanced FcRn binding, ARGX-121 actively removes IgA from circulation. In addition, ARGX-121 can also block the interaction of IgA with its main Fc receptor (FcαRI; CD89). Targeting IgA with ARGX-121 through this dual mechanism of action could provide therapeutic opportunities in IgA-mediated diseases. This first-in-human (FIH) study was designed to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single and multiple ascending doses (SAD and MAD, respectively) of ARGX-121 in healthy adults.
Methods
This phase 1, FIH, randomized, double-blind, placebo-controlled study was conducted at a single site in the Netherlands. Eligible healthy adults were randomized 3:1 to receive ARGX-121 (intravenously or subcutaneously ± comixed with recombinant human hyaluronidase PH20) or placebo in 9 SAD and 5 MAD cohorts (each n=8). Treatment administration occurred on Day 1 for the SAD cohorts and on Days 1, 8, 15, and 22 for the MAD cohorts, with a follow-up period of 63 days after the last administration. The primary endpoint was to assess safety and tolerability of ARGX-121. Secondary endpoints included PK, PD, and immunogenicity parameters.
Results
Potent total IgA reduction was observed, with total IgA levels decreased by ≥85% within a week or less and sustained for multiple weeks with single doses of ARGX-121. ARGX-121 was well tolerated in healthy adult participants, with no serious or grade ≥3 adverse events reported. No adverse events led to study discontinuation. Additional PK, PD, immunogenicity, and safety parameters will be presented.
Conclusion
These FIH results support further clinical development of ARGX-121 in IgA-mediated diseases.
Funding
- Commercial Support – argenx