Clinical Study of Recombinant CD19xCD3 Double Antibody (A-319) in the Treatment of Active/Refractory Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Safety and tolerability
研究概览
简要总结
The purpose of the study is to explore the safety and efficacy of recombinant CD19xCD3 double antibody (A-319) in active/refractory systemic lupus erythematosus (SLE).
详细描述
The pathogenic B cells of patients with SLE can produce a large amount of autoantibodies, which will form immune complexes and thereby inducing continuously expanding tissue damage and systemic inflammation. A-319 is a kind of recombinant CD19xCD3 double antibody, it can activate internal T cells to target and kill pathogenic B cells. Clinical trials of A-319 are currently underway in hematological maliganancies concerning B cell abnormality. Preclinical studies have shown the efficacy of A-319 in SLE. The aim of this study is to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and preliminary efficacy of A-319 in active/refractory SLE. Patients with active/refractory SLE will be invited to participate in the study, to receive A-319 intravenous infusion or subcutaneous injection and follow-up visits of up to 1 years after enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-60 years old, regardless of gender;
- •Participants diagnosed with SLE according to the American College of Rheumatology (ACR) 1997 revised criteria for SLE at least 24 weeks prior to signing the informed consent form;
- •Active/refractory systemic lupus erythematosus;
- •Positive test results for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) immunofluorescence assay at a titer of ≥1:80; anti-dsDNA; or anti-Smith (anti-Sm);
- •Receive the standardized and stable treatment for at least 30 days before the first administration of the study drug;
- •Female participants tested negative for pregnancy, and participants agreed to use effective contraception throughout the trial;
- •Have the ability to understand the nature of the research and voluntarily sign an informed consent form;
- •Participants can communicate well with the researchers and complete all visits according to the requirements of the plan.
排除标准
- •Severe kidney disease;
- •Participants who have central nervous system diseases caused by SLE or non-SLE disease within 8 weeks before the first administration of the study drug;
- •Abnormities of main organ function at screening;
- •Medical history that the researchers believe will pose risk to the safety of the participants, or will affect the safety or effectiveness analysis of the study drug;
- •Active mycobacterium tuberculosis infection;
- •Active hepatitis, or hepatitis B virus surface antigen positive, or hepatitis B virus core antibody positive and hepatitis B virus deoxyribonucleic acid positive, ,or hepatitis C virus (HCV) antibody positive with detectable HCV ribonucleic acid (RNA).;
- •History of human immunodeficiency virus infection, or positive antibodies at screening;
- •Positive syphilis spirochete antibody at screening (except false positive caused by SLE);
- •Participants with chronic active infection or acute infection need systemic anti-infection treatment within 2 weeks before screening, or have superficial skin infection requiring treatment within 1 week before screening;
- •Have undergone major surgery or unhealed wounds, ulcers or fractures within 4 weeks before the first administration of the study drug, or plan to perform major surgery during the study period;
- •Participants diagonosed with malignant tumors within 5 years before screening;
- •History of important organ transplantation or hematopoietic stem cells/or bone marrow transplantation;
- •Have been vaccinated or plan to receive live vaccine or live attenuated vaccine during the research period within 4 weeks before the first administration of the study drug;
- •Participated in any clinical trial within 4 weeks before the first administration of the study drug or within 5 half-lives of the study drug of the clinical trial;
- •Received targeted drugs (rituximab, JAK inhibitors, etc.) at a specific time period before the first administration of the study drug;
- •Received intravenous immunoglobulin, prednisone ≥100mg/d or equivalent glucocorticoid therapy within 4 weeks before the first administration of the study drug, or plasma replacement;
- •Received IL-2, thalidomide, rethidone and traditional Chinese medicine within 4 weeks before the first administration of the study drug;
- •Known allergies to monoclonal antibody drugs, or allergies to A-319 excipients;
- •Participants with depression or suicidal thoughts;
- •Women who are pregnant or breastfeeding, or women who plan to be pregnant or breastfeeding during the study period; or men whose sexual partners plan to become pregnant during the study period;
- •Any reason that the researchers believe will hinder the subject's participation in the study.
研究组 & 干预措施
A-319 intravenous intervention
A-319 will be preset with 3 escalation dose levels by intravenous infusion: dose A, dose B, dose C, total course of treatment: 4 weeks. Anticipated enrollment: 9-18 participants.
干预措施: A-319 (Biological)
A-319 subcutaneous intervention
A-319 will be administered via subcutaneous injection at five preset escalating dose levels: Dose A, Dose B, Dose C, Dose D, and Dose E. The total treatment duration is 4 weeks. Each dose group is planned to enroll 3+N (N=0-12) participants, with a total anticipated enrollment of 16-32 study participants.
干预措施: A-319 (Biological)
结局指标
主要结局
Safety and tolerability
时间窗: Within 1 year since A-319 infusion
Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs)
次要结局
- Pharmacokinetics of A-319(Within 1 month since A-319 infusion)
- Numbers of Participants with positive antidrug antibodies in peripheral blood(Day 28 and month 3 since A-319 infusion)
- Pharmacodynamics of A-319(Within 1 month since A-319 infusion)
研究者
Qiubai Li
Director, Head of Department of Rheumatology and Immunology, Principal Investigator, Professor, Wuhan Union Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology