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

NCT ID: NCT06400537

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-20
• Study Completion Date: 2026-12-31

Brief Summary

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).

Detailed Description

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

A-319

Intervention Type: BIOLOGICAL

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

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.

Group Type: EXPERIMENTAL

A-319

Intervention Type: BIOLOGICAL

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

Interventions

A-319

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Age 18-60 years old, regardless of gender;

2. 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;

3. Active/refractory systemic lupus erythematosus;

4. 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);

5. Receive the standardized and stable treatment for at least 30 days before the first administration of the study drug;

6. Female participants tested negative for pregnancy, and participants agreed to use effective contraception throughout the trial;

7. Have the ability to understand the nature of the research and voluntarily sign an informed consent form;

8. Participants can communicate well with the researchers and complete all visits according to the requirements of the plan.

Exclusion Criteria

1. Severe kidney disease;

2. 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;

3. Abnormities of main organ function at screening;

4. 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;

5. Active mycobacterium tuberculosis infection;

6. 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).;

7. History of human immunodeficiency virus infection, or positive antibodies at screening;

8. Positive syphilis spirochete antibody at screening (except false positive caused by SLE);

9. 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;

10. 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;

11. Participants diagonosed with malignant tumors within 5 years before screening;

12. History of important organ transplantation or hematopoietic stem cells/or bone marrow transplantation;

13. 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;

14. 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;

15. Received targeted drugs (rituximab, JAK inhibitors, etc.) at a specific time period before the first administration of the study drug;

16. Received intravenous immunoglobulin, prednisone ≥100mg/d or equivalent glucocorticoid therapy within 4 weeks before the first administration of the study drug, or plasma replacement;

17. Received IL-2, thalidomide, rethidone and traditional Chinese medicine within 4 weeks before the first administration of the study drug;

18. Known allergies to monoclonal antibody drugs, or allergies to A-319 excipients;

19. Participants with depression or suicidal thoughts;

20. 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;

21. Any reason that the researchers believe will hinder the subject's participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ITabMed Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Qiubai Li

Director, Head of Department of Rheumatology and Immunology, Principal Investigator, Professor, Wuhan Union Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qiubai Li, Professor

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Wuhan Union Hospital

Wuhan, Hubei, China

Site Status: RECRUITING

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Qiubai Li, Professor

Role: CONTACT

qiubaili@hust.edu.cn

85726808 ext. 027

Di Wu

Role: CONTACT

373181302@qq.com

18790696175 ext. 86

Facility Contacts

Qiubai Li, Professor

Role: primary

qiubaili@hust.edu.cn

85726808 ext. 027

Chunli Mei, PhD

Role: backup

85726808 ext. 027

Liyun Zhang, Professor

Role: primary

1315710223@qq.com

Other Identifiers

UHCT240243

Identifier Type: -

Identifier Source: org_study_id