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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: A-319

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn
• Study Contact Backup: Name: Di Wu; Phone Number: 86 18790696175; Email: 373181302@qq.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Wuhan Union Hospital
      • Contact: Qiubai Li, professor; Phone Number: 027 85726808; Email: qiubaili@hust.edu.cn
      • Contact: Chunli Mei, PhD; Phone Number: 027 85726808
  • Shanxi
    • Taiyuan, Shanxi, China, 030032
      • Recruiting
      • Shanxi Bethune Hospital
      • Contact: Liyun Zhang, Professor; Email: 1315710223@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: A-319; A-319 will be dosed according to the assigned group.
Experimental: 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.	Biological: A-319; A-319 will be dosed according to the assigned group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs)	Within 1 year since A-319 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of A-319	Concentration of A-319 in peripheral blood will be evaluated	Within 1 month since A-319 infusion
Pharmacodynamics of A-319	Pharmacodynamics will be assessed by levels of cytokines (IL-6, IL-8, IL-10, IFN-γ, TNF-α) in peripheral blood	Within 1 month since A-319 infusion
Pharmacodynamics of A-319	Pharmacodynamics will be assessed by levels of lymphocyte subsets in peripheral blood	Within 1 month since A-319 infusion
Numbers of Participants with positive antidrug antibodies in peripheral blood	To evaluate immunogenicity of A-319	Day 28 and month 3 since A-319 infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) from baseline	Range [0, 105]，higher score represents worse disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in the Physician Global Assessment (PGA) score from baseline	Range [0, 3]，higher score represents worse disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in the BILAG-2004 score from baseline	Range [0, 72]，higher score represents worse disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in immunological indexes from baseline	Serum IgA, IgG, IgE and IgM will be evaluated	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline	To evaluate SLE disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline	To evaluate SLE disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in levels of complement C3 in peripheral blood from baseline	To evaluate SLE disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
Changes in levels of complement C4 in peripheral blood from baseline	To evaluate SLE disease activity	Within 1 year since A-319 infusion (day 15, day 28, month 2, month 3, month 4, month 5, month 6, month 9, month 12)
The therapeutic effect of A-319 on impaired organs in active/refractory SLE patients	Pathological samples of impaired organs will be analyzed	Within 1 year since A-319 infusion
The clearance effect of A319 on CD19+B cells in active/refractory SLE patients	To evaluate SLE disease activity	Within 28 days since A-319 infusion
The effect of A-319 on gene expression in peripheral blood lymphocytes of active/refractory SLE	To investigate the mechanism of action of A-319 in SLE	Day 28 and month 3 since A-319 infusion

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Collaborators: ITabMed Co., Ltd.
• Investigators: Principal Investigator: Qiubai Li, Professor, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; A-319
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: UHCT240243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No