A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren’s Syndrome With Moderate-to-severe Systemic Disease Activity.

Protocol HZN-DAZ-301 is a Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of dazodalibep in participants with SS with moderate-to-severe systemic disease activity. The study design is provided in Section 1.2 (Figure 1). The study will enroll SS participants with moderate-to-severe systemic disease activity defined by ESSDAI score ? 5. Individuals will undergo a screening period of up to 28 days followed by randomization and treatment through the Week 44 visit. Approximately 510 participants will be randomized (1:1:1) to dazodalibep Dose 1, dazodalibep Dose 2, or placebo as follows: ? Dazodalibep Dose 1: 1500 mg intravenously (IV) at Weeks 0, 2, and 4 then once every 4 weeks [Q4W]) for a total of 13 total doses (n = 170) ? Dazodalibep Dose 2: 3000 mg IV at Weeks 0, 4, and 12 then once every 12 weeks [Q12W]) for a total of 13 doses: 5 doses of dazodalibep; 8 doses of placebo (n = 170) ? Placebo for a total of 13 doses (n = 170) Study participants, Investigators, and Sponsor will be blinded to each participant’s treatment assignment. Randomization will be stratified by screening ESSDAI score of < 14 or ? 14, geographic region (North America and Europe versus Japan versus Rest of World), and coexisting rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (yes versus no). The study plans to enroll at least 25% participants with high disease activity (ESSDAI score ? 14). Participants will not be replaced after randomization. Participants will receive randomized treatment (dazodalibep or placebo) through Week 44. The primary endpoint visit will be at Week 48. At the Week 44 visit, eligible participants may provide written informed consent to screen for an open-label extension (OLE) study (HZNP-DAZ-304) for receipt of open-label dosing with dazodalibep. Participants ineligible for or not wishing to enroll in the OLE extension will have a final study visit at Week 56 to complete 12 weeks of safety follow-up after the last dose of investigational product (IP). In this case, the expected full duration of each individual’s participation in this study, including screening but not the OLE, is up to 420 days. Eligible participants interested in participating in the OLE will complete participation in this Phase 3 study at the Week 48 visit, after completion of all visit assessments. These Week 48 visit values will serve as baseline (Day 1) for the OLE study; Dose 1 of open-label dazodalibep will be administered at or at approximately the Week 48 visit, their final visit in this Phase 3 study. All participants must be followed to per-protocol completion of study (Week 48 visit for those who enroll in and are dosed in the OLE study and the Week 56 visit for those not dosed in the OLE study), whether or not they have discontinued treatment, or had an adverse event (AE), or for any other reason except withdrawal from study participation or loss to follow-up. Participants who refuse to participate in some aspects of the study should, unless consent for all participation is withdrawn, participate in those aspects for which they continue to consent. All participants, including those who enroll in the OLE, will remain blinded to their treatment assignment until the Phase 3 study is complete. The primary objective of this study is to evaluate the effect of dazodalibep on systemic manifestations of SS in participants with moderate-to-severe systemic disease activity. This will be assessed by evaluating the change from baseline in ESSDAI score at Week 48.