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

Systemic Lupus Erythematosus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06400537
• Other study ID #: UHCT240243
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: May 2026

Study information

• Verified date: May 2024
• Source: Wuhan Union Hospital, China
• Contact: Qiubai Li, Professor
• Phone: 85726808
• Email: qiubaili[@]hust.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 and follow-up visits of up to 1 years after enrollment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: May 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 antibody positive at screening;

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 4 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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Biological:
• A-319
A-319 will be infused intravenously.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China	ITabMed Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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
Other	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
Other	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
Primary	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	Pharmacokinetics of A-319	Concentration of A-319 in peripheral blood will be evaluated	Within 1 month since A-319 infusion
Secondary	Pharmacodynamics of A-319	Pharmacodynamics will be assessed by levels of cytokines (IL-6, IL-8, IL-10, IFN-?, TNF-a) in peripheral blood	Within 1 month since A-319 infusion
Secondary	Pharmacodynamics of A-319	Pharmacodynamics will be assessed by levels of lymphocyte subsets in peripheral blood	Within 1 month since A-319 infusion
Secondary	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