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NCT07818694

PHASE1

JH013 Injection in Patients With Primary Sjögren's Syndrome

Sponsor: Biotech Pharmaceutical Co., Ltd.

View on ClinicalTrials.gov

Summary

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.

Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of JH013 Injection in Patients With Primary Sjögren's Syndrome

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-09-30

Completion Date

2028-12-28

Last Updated

2026-09-14

Healthy Volunteers

Conditions

Primary Sjögren's Syndrome (pSS)

Interventions

BIOLOGICAL

JH013 injection

Anti-B-cell Activating Factor Receptor（Anti-BAFFR） Monoclonal Antibody

Inclusion Criteria: * Patients with primary Sjögren's syndrome (pSS) who meet the 2016 ACR/EULAR classification criteria for primary Sjögren's syndrome; 18 to 65 years of age (inclusive) for Part A and 18 to 75 years of age (inclusive) for Part B; * EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥6 during the Screening Period; * EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ≥5 during the Screening Period; * Elevated serological markers during the Screening Period, defined as an antinuclear antibody (ANA) titer ≥1:160 and positive rheumatoid factor (RF), or positive anti-SSA antibody (with or without anti-SSB antibody); * Stimulated whole salivary flow rate ≥0.05 mL/min or unstimulated whole salivary flow rate ≥0.01 mL/min during the Screening Period; * Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours prior to dosing. Postmenopausal women (defined as amenorrhea for at least 12 months) and women with a known history of hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation are considered not to be of childbearing potential and are not required to undergo a pregnancy test; * Participants must understand and comply with the study procedures, voluntarily participate in the study, and provide written informed consent. Exclusion Criteria: * Secondary Sjögren's syndrome, defined as Sjögren's syndrome overlapping with another autoimmune disease or systemic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, or idiopathic inflammatory myopathy); * Use of another investigational medicinal product within 5 half-lives or 30 days prior to Screening, whichever is longer, or within a period during which the expected pharmacodynamic effect has not returned to baseline, whichever is longer; or for a longer period if required for the investigational medicinal product; * Use of B-cell-depleting therapies within 24 weeks prior to Screening (e.g., VAY736, rituximab, other anti-CD20 monoclonal antibodies, anti-CD22 monoclonal antibodies, or anti-CD52 monoclonal antibodies), or B-cell counts have not recovered to the lower limit of normal or baseline following prior B-cell-depleting therapy, whichever is lower; * Receipt of any of the following prior treatments before Screening: 1. Within 24 weeks: iscalimab (anti-CD40 monoclonal antibody), belimumab (anti-BAFF monoclonal antibody), telitacicept, abatacept (CTLA4-Fc-Ig), anti-tumor necrosis factor-alpha (TNF-α) biologics, intravenous or subcutaneous immunoglobulin (IVIG/SCIG), or plasma exchange; 2. Within 12 weeks: intravenous or oral cyclophosphamide, mycophenolate mofetil (MMF), intravenous or oral cyclosporine A, or any other immunomodulatory/immunosuppressive medication (e.g., JAK inhibitors or other kinase inhibitors); * Prednisone dose \>10 mg/day, or any adjustment to the prednisone dose within 2 weeks prior to Screening; * Currently receiving azathioprine, or use of azathioprine within 3 months prior to Screening. Patients who have been receiving a stable dose of hydroxychloroquine or methotrexate for ≥3 months prior to Screening and who will maintain the same dose throughout the study may be eligible; * Use of traditional Chinese medicines (TCM) or proprietary Chinese medicines for the treatment of primary Sjögren's syndrome within 4 weeks prior to Screening, including Tripterygium wilfordii polyglycosides and total glucosides of paeony; * Use of sialagogues within 7 days prior to Screening, such as anethole trithione or pilocarpine; * Severe systemic involvement of Sjögren's syndrome, as assessed by the Investigator, including but not limited to: 1. Severe vasculitis involving the kidneys, gastrointestinal system, heart, lungs, or central nervous system (excluding cutaneous vasculitis); 2. Active central or peripheral nervous system involvement requiring high-dose glucocorticoid therapy; 3. Severe renal involvement, such as estimated glomerular filtration rate (eGFR) \<60 mL/min, serum creatinine \>2 mg/dL, or urinary protein \>3 g/day; 4. Severe pulmonary involvement, such as dyspnea at rest, or pulmonary function test results showing forced vital capacity (FVC) \<60% or diffusing capacity of the lung for carbon monoxide (DLCO) \<40%; 5. Myositis requiring high-dose glucocorticoid therapy; 6. Lymphoma; * Abnormal laboratory parameters: 1. Hematology: hemoglobin \<8.0 g/dL, white blood cell (WBC) count \<2.0 × 10⁹/L, platelet count \<75 × 10⁹/L, or absolute neutrophil count (ANC) \<1.0 × 10⁹/L; 2. Clinical chemistry: total bilirubin \>1.5 × ULN, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 × ULN; * Active viral, bacterial, or other infection requiring systemic treatment, or a clinically significant history of recurrent infections; * Known hypersensitivity to any component of JH013 or its excipients, including histidine, dilute hydrochloric acid, arginine hydrochloride, or sucrose; * History of organ, hematopoietic stem cell, or bone marrow transplantation; * Requirement for regular use of medications known to cause dry mouth or dry eyes, including but not limited to beta-blockers, antihistamines, pseudoephedrine, selective antidepressants, anticholinergic agents, sedatives, antipsychotics, antiparkinsonian medications, and diuretics; * Use of topical ophthalmic prescription medications, excluding artificial tears, gels, and lubricants, with no stable dose for at least 90 days prior to Screening, or any anticipated change in the treatment regimen during the study; * Receipt of a live or live-attenuated vaccine within 30 days prior to Screening; * History of malignancy in any organ system within the past 5 years, whether treated or untreated and regardless of evidence of local recurrence or metastasis, except for locally treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or Sjögren's syndrome-associated lymphoma; * History of sarcoidosis; * Any condition considered by the Investigator to be unsuitable for participation in the study, including surgery, medical conditions (e.g., inadequately controlled hypertension, heart failure, or diabetes), psychiatric disorders, or other conditions; * Positive test results for human immunodeficiency virus (HIV) antibodies; positive hepatitis B virus (HBV) surface antigen (HBsAg), or positive HBV core antibody (anti-HBc) with positive HBV DNA; positive hepatitis C virus (HCV) antibody; or positive syphilis serology; * History of tuberculosis (TB) or a positive interferon-gamma release assay (IGRA) at Screening. An IGRA result obtained within 3 months prior to Screening is acceptable; * Known history of poor medication adherence, or inability or unwillingness to complete the study questionnaires; * Pregnancy or breastfeeding; planned pregnancy; or women of childbearing potential or sexually active men who are unwilling to use reliable contraception during the study and for 3 months after the last dose of study drug, or who intend to donate sperm during the same period.