JH013 Injection in Patients With Primary Sjögren's Syndrome

Primary Sjögren's Syndrome (pSS)

This is a multicenter, open-label, single-arm Phase I study consisting of two parts: Part A, a single-dose dose-escalation phase, and Part B, a multiple-dose dose-escalation phase. The study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and clinical efficacy of JH013 Injection in patients with primary Sjögren's syndrome (pSS). Part A: Six dose levels are planned: 15, 45, 90, 150, 225, and 315 mg. A 3+3 dose-escalation design will be used, with 3 participants initially enrolled at each dose level to receive a single subcutaneous injection into the abdominal wall. If no dose-limiting toxicity (DLT) occurs, escalation may proceed. If 1 of 3 participants experiences a DLT, 3 additional participants may be enrolled at the same dose. If ≥2 of 6 participants experience a DLT, escalation will be stopped or a lower dose may be explored. DLTs are defined as Grade ≥3 cytokine release syndrome (CRS), or Grade ≥3 infection, hypersensitivity reaction, or other study-drug-related adverse event that does not recover within 1 week of treatment, according to Common Terminology Criteria for Adverse Events（CTCAE） Version 6.0. Additional participants may be enrolled if PK/PD results suggest a potentially therapeutic dose or if additional data are considered necessary. One participant will initially be enrolled at each dose level and observed for 72 hours before further participants are enrolled. Up to 36 participants are planned. Dose escalation will proceed only after acceptable safety and tolerability for at least 21 days after the preceding dose are confirmed by the investigator and sponsor. Part B: Three ascending dose levels will be selected based on the Phase I healthy participant study and Part A results. A 3+3 design will be used, with 3 participants initially enrolled at each dose level. JH013 will be administered subcutaneously into the abdominal wall once every 4 weeks for a total of 6 doses. The same DLT definitions and escalation rules as Part A will apply. Up to 18 participants are planned. Escalation will proceed only after acceptable safety and tolerability of the preceding dose are confirmed within 2 weeks after the second dose. If predefined dose-escalation termination criteria are met, an intermediate or lower dose may be explored to further determine the maximum tolerated dose. If the highest planned dose is reached without meeting the termination criteria, a higher dose may be considered. If any study-drug-related serious adverse event (SAE) occurs, study activities will be suspended and the investigator and sponsor will jointly assess the event and its impact on further study conduct. All participants will receive recommended premedication with intravenous methylprednisolone 250 mg 1-2 hours before the first dose, or an equivalent glucocorticoid. The regimen may be adjusted based on the participant's clinical condition. Vital signs and laboratory parameters, including Interleukin-6（IL-6）, Interleukin-10（IL-10）, and Tumor Necrosis Factor-alpha（TNF-α,） will be monitored for early identification of CRS. CRS will be assessed and managed according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS grading criteria, with treatment ranging from symptomatic management and close monitoring for Grade 1 to intensive care and life-supportive treatment for Grade 4, with corticosteroids and tocilizumab used as clinically indicated. Participants will undergo screening within 21 days before the first dose. In Part A, participants will be admitted on Day -1, receive baseline PK/PD sampling before dosing, and remain at the study center until Day 3 for PK/PD sampling and safety assessment. Follow-up assessments of PK, PD, immunogenicity, efficacy, and safety will continue through Day 169. Participants with inadequate recovery of Cluster of Differentiation 19 positive （CD19+） B-cell counts after Day 85 may continue follow-up every 3 months for up to 6 months. In Part B, participants will receive 6 doses at 4-week intervals. They will remain at the study center through Day 3 after the first and final doses for PK/PD sampling and safety assessment; other dosing visits may be conducted on an outpatient basis or with 1-2 days of inpatient observation based on safety findings. After treatment completion, participants will undergo follow-up for 24 weeks to monitor CD19+ B-cell recovery, safety, PK/PD, immunogenicity, and clinical efficacy.

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