1455: Sonelokimab in Patients With Active Psoriatic Arthritis Who Are Naive to Biologic DMARDs: Phase 2 ARGO Analysis and Phase 3 IZAR-1 Study Design

Background/Purpose: Sonelokimab (SLK), a novel Nanobody that binds to both IL-17A and IL-17F with similarly high affinity, is designed to target difficult-to-reach sites of inflammation due to its small size and albumin-binding domain. ARGO was a Phase 2 trial of SLK in active PsA, which met its primary endpoint of ACR50 vs. placebo at Week (W) 12 for SLK 60mg and 120mg (with induction [WI]). Here, we report W24 data in the ARGO trial from a subset of patients naive to bDMARDs (prior biologic use was a stratification factor). We also describe the design of the Phase 3 IZAR-1 trial, which will further evaluate SLK 60mg WI and SLK 60mg with no induction (NI) in this patient population.

Methods: ARGO (NCT05640245) was a 24-week, global, randomized, placebo-controlled, double-blind trial of adults with active PsA (TJC68 ≥3 and SJC66 ≥3). Three SLK doses were assessed: 60mg NI (Q4W), SLK 60mg WI, and SLK 120mg WI (induction doses at W0, 2, 4, and 6; Q4W from W8). In this exploratory analysis, we assessed outcomes at W24 in patients without prior bDMARD exposure treated with SLK 60mg with or without induction (IZAR-1 doses).

Results: Of the 207 patients enrolled in ARGO (Table), 171 patients (82.6%) were naive to bDMARDs. SLK 60mg resulted in clinical responses at W24 in patients naive to bDMARDs (SLK 60mg WI, n=34; SLK 60mg NI, n=33), including ACR50 (SLK 60mg WI: 61.8%; SLK 60mg NI: 63.6%), the higher threshold of ACR70 (SLK 60mg WI: 41.2%; SLK 60mg NI: 45.5%), and the composite endpoint of minimal disease activity ([MDA]; SLK 60mg WI: 58.8%; SLK 60mg NI: 48.5%). For patients naive to bDMARDs with skin involvement (SLK 60mg WI, n=22; SLK 60mg NI, n=28), treatment with SLK resulted in notable PASI 90 (SLK 60mg WI: 81.8%; SLK 60mg NI: 67.9%) and PASI 100 responses (SLK 60mg WI: 68.2%; SLK 60mg NI: 57.1%). SLK was well tolerated, with a safety profile consistent with IL-17 inhibition. Based on these findings, we have designed a 52-week, global, randomized, double-blind, PBO‑controlled, Phase 3 trial in this patient population (IZAR-1; NCT06641076; Figure). An estimated 960 patients will be randomized 1:1:1 to receive SLK 60mg Q4W WI, SLK 60mg Q4W NI, or PBO (SLK 60mg WI from W16). Given the results from ARGO, this sample size should provide sufficient power to demonstrate a statistically significant difference for each SLK arm vs. PBO on the primary outcome of ACR50 at W16. Eligible participants will have a confirmed diagnosis of PsA (CASPAR criteria), active disease (TJC68 ≥3; SJC66 ≥3), currently active or dermatologist-confirmed historical psoriasis, inadequate response to ≥1 conventional DMARD, and ≥1 erosion on hands-and-feet X-ray or hs-CRP > the ULN. Key secondary outcomes (all vs. PBO at W16) include ACR20, PASI 90, and MDA; the PROs HAQ-DI and SF-36 Physical Component Summary; and radiographic progression (vdH-mTSS).

Conclusion: The Phase 2 ARGO study demonstrated high levels of clinical response with SLK, including in patients with active PsA naive to bDMARDs. The randomized Phase 3 IZAR-1 study will further assess outcomes with SLK in patients naive to bDMARDs and is actively recruiting, including at sites across the USA.