Systemic Lupus Erythematosus
Conditions
Keywords
systemic lupus erythematosus, A-319
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.
Interventions
BIOLOGICALA-319
A-319 will be dosed according to the assigned group.
Sponsors
ITabMed Co., Ltd.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | Within 1 year since A-319 infusion | Safety and tolerability will be assessed by incidence and severity of adverse events (AEs) and serious AEs (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of A-319 | Within 1 month since A-319 infusion | Concentration of A-319 in peripheral blood will be evaluated |
| Pharmacodynamics of A-319 | Within 1 month since A-319 infusion | Pharmacodynamics will be assessed by levels of cytokines (IL-6, IL-8, IL-10, IFN-γ, TNF-α) in peripheral blood |
| Numbers of Participants with positive antidrug antibodies in peripheral blood | Day 28 and month 3 since A-319 infusion | To evaluate immunogenicity of A-319 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline | 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) | To evaluate SLE disease activity |
| Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline | 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) | To evaluate SLE disease activity |
| Changes in levels of complement C3 in peripheral blood from baseline | 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) | To evaluate SLE disease activity |
| Changes in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) from baseline | 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) | Range \[0, 105\]，higher score represents worse disease activity |
| The therapeutic effect of A-319 on impaired organs in active/refractory SLE patients | Within 1 year since A-319 infusion | Pathological samples of impaired organs will be analyzed |
| The clearance effect of A319 on CD19+B cells in active/refractory SLE patients | Within 28 days since A-319 infusion | To evaluate SLE disease activity |
| The effect of A-319 on gene expression in peripheral blood lymphocytes of active/refractory SLE | Day 28 and month 3 since A-319 infusion | To investigate the mechanism of action of A-319 in SLE |
| Changes in levels of complement C4 in peripheral blood from baseline | 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) | To evaluate SLE disease activity |
| Changes in the Physician Global Assessment (PGA) score from baseline | 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) | Range \[0, 3\]，higher score represents worse disease activity |
| Changes in the BILAG-2004 score from baseline | 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) | Range \[0, 72\]，higher score represents worse disease activity |
| Changes in immunological indexes from baseline | 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) | Serum IgA, IgG, IgE and IgM will be evaluated |
Countries
China
Contacts
Primary ContactQiubai Li, Professor
Backup ContactDi Wu
Outcome results
None listed