Clinical Study of A-319 in the Treatment of Active/Refractory Systemic Lupus Erythematosus

Официальное название

Clinical Study of Recombinant CD19xCD3 Double Antibody (A-319) in the Treatment of Active/Refractory Systemic Lupus Erythematosus

Обзор

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).

Подробное описание

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.

Вмешательства

• Биопрепарат A-319
  A-319 will be dosed according to the assigned group.

Первичные конечные точки

• Safety and tolerability [Срок оценки: Within 1 year since A-319 infusion]

Вторичные конечные точки (4)

• Pharmacokinetics of A-319 [Срок оценки: Within 1 month since A-319 infusion]
• Pharmacodynamics of A-319 [Срок оценки: Within 1 month since A-319 infusion]
• Pharmacodynamics of A-319 [Срок оценки: Within 1 month since A-319 infusion]
• Numbers of Participants with positive antidrug antibodies in peripheral blood [Срок оценки: Day 28 and month 3 since A-319 infusion]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Wuhan Union Hospital — Ухань
• Shanxi Bethune Hospital — Taiyuan

Идентификаторы

NCT: NCT06400537 · UHCT240243

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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