Clinical trial NCT06400537: Clinical Study of A-319 in the Treatment of Active/Refractory Systemic Lupus Erythematosus
Official title: Clinical Study of Recombinant CD19xCD3 Double Antibody (A-319) in the Treatment of Active/Refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: systemic lupus erythematosus
A-319
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: ITabMed Co., Ltd.
First posted: 2024-05-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Safety and tolerability
timeFrame: Within 1 year since A-319 infusion
Secondary outcomes:
measure: Pharmacokinetics of A-319
timeFrame: Within 1 month since A-319 infusion
measure: Pharmacodynamics of A-319
timeFrame: Within 1 month since A-319 infusion
measure: Pharmacodynamics of A-319
timeFrame: Within 1 month since A-319 infusion
measure: Numbers of Participants with positive antidrug antibodies in peripheral blood
timeFrame: Day 28 and month 3 since A-319 infusion
Other outcomes:
measure: Changes in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) from baseline
timeFrame: 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)
measure: Changes in the Physician Global Assessment (PGA) score from baseline
timeFrame: 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)
measure: Changes in the BILAG-2004 score from baseline
timeFrame: 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)
measure: Changes in immunological indexes from baseline
timeFrame: 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)
measure: Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline
timeFrame: 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)
measure: Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline
timeFrame: 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)
measure: Changes in levels of complement C3 in peripheral blood from baseline
timeFrame: 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)
measure: Changes in levels of complement C4 in peripheral blood from baseline
timeFrame: 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)
measure: The therapeutic effect of A-319 on impaired organs in active/refractory SLE patients
timeFrame: Within 1 year since A-319 infusion
measure: The clearance effect of A319 on CD19+B cells in active/refractory SLE patients
timeFrame: Within 28 days since A-319 infusion
measure: The effect of A-319 on gene expression in peripheral blood lymphocytes of active/refractory SLE
timeFrame: Day 28 and month 3 since A-319 infusion
Locations:
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
Study officials:
affiliation: Wuhan Union Hospital, China
name: Qiubai Li, Professor
role: PRINCIPAL_INVESTIGATOR
References: