Efficacy and safety of efgartigimod PH20 SC for Sjögren’s disease-associated dryness: study protocol for an investigator-initiated, multicenter, phase 2, randomized, double-blind, placebo-controlled trial (OASIS study)

Background: Sjögren's disease (SjD) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration and progressive destruction of the lacrimal and salivary glands, leading to ocular and oral dryness as hallmark symptoms. Despite low systemic activity, these sicca symptoms significantly impair the quality of life, particularly in patients with severe dryness. Currently, no disease-modifying therapy is approved for SjD. Efgartigimod PH20, the neonatal Fc receptor (FcRn) blocker, has shown promising efficacy and safety in patients with moderate-to-severe systemic SjD. However, its efficacy for dryness in patients with SjD remains unknown. Methods/design: This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, investigator-initiated trial conducted in Japan. Approximately 45 adult patients with SjD and moderate-to-severe dryness will be randomized in a 1:1:1 ratio to receive subcutaneous efgartigimod PH20 at 1,000 mg weekly (QW), 1,000 mg every other week (Q2W), or placebo for 24 weeks. The primary endpoint is the change in EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI)-dryness score from baseline to week 24. Key secondary endpoints include changes in ESSPRI-total, ESSPRI-fatigue, Diary of Sjögren's Symptoms Assessment (DiSSA) scores, and the proportion of responders in ESSPRI and Sjögren's Tool for Assessing Response (STAR) assessments. After the blinded period, all participants will be offered an open-label extension treatment to assess long-term safety and efficacy. Discussion: This trial specifically targets patients with SjD who have prominent sicca symptoms. By using FcRn blockade to reduce pathogenic IgG autoantibodies, this study aims to explore the potential of efgartigimod PH20 as a novel therapeutic approach for dryness-predominant SjD. The findings are expected to provide future treatment strategies to address the major unmet need regarding dryness-related burden in this patient population. Clinical trial registration: Japan Registry of Clinical Trials (jRCT2071250042); registered on 08 July 2025, https://jrct.mhlw.go.jp/en-latest-detail/jRCT2071250042.