Clinical Study of (A-319) in the Treatment of Active Rheumatoid Arthritis

Clinical Study of Recombinant Anti-CD19m-CD3 Antibody Injection (A-319) in the Treatment of Active Rheumatoid Arthritis

The primary objective of the study was to evaluate the safety and tolerability of A-319 in patients with active rheumatoid arthritis.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Biological: A-319

Detailed Description

Active rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis as its primary clinical manifestation. A-319 is a recombinant CD19xCD3 bispecific antibody that activates T cells in vivo and targets and kills pathogenic B cells. A-319 is currently in clinical trials for B-cell hematologic malignancies. Preclinical results in animal models of systemic lupus erythematosus (SLE) and RA have also demonstrated that A-319 can alleviate or eliminate autoimmune disease-related symptoms and progression by depleting pathogenic B cells in individuals with autoimmune diseases. This investigator-initiated trial (IIT) evaluated the safety, tolerability, pharmacokinetic profile, biological markers, and preliminary efficacy of A-319 in the treatment of patients with rheumatoid arthritis (RA) who have refractory responses to at least two different therapies with different mechanisms of action.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Qiubai Li Professor, 85726808; Phone Number: 027 Ext; Email: qiubaili@hust.edu.cn

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-70 years (inclusive), gender unrestricted.
2. Meet the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, with a diagnosis of rheumatoid arthritis for at least 24 weeks.
3. Patients with rheumatoid arthritis who have previously responded inadequately to at least one csDMARD and who have not responded to 12 weeks of combined treatment with at least one bDMARD or/and tsDMARD with a different mechanism of action in addition to their original csDMARD, such as those with insignificant improvement in swollen/tender joints, physical condition, or disease activity.
4. Experiencing at least one of the following clinical manifestations suggestive of moderate to severe RA disease activity:

1) C-reactive protein-based 28-joint disease activity index (DAS28-CRP) >3.2 or clinical disease activity index (CDAI) >10; 2) Clinical manifestations and/or symptoms suggestive of disease activity, including acute inflammatory markers (ESR, CRP) and imaging findings, and joint-related or other symptoms. 5. At the screening and baseline visits, patients must have ≥ 6 tender joints (TJCs) per 68 units and ≥ 4 swollen joints (SJCs) per 66 units.

6. If the patient is taking oral glucocorticoids, the dose of prednisone or its equivalent must be ≤ 7.5 mg/day and maintained stable for at least 2 weeks before the first dose.

7. Patients must have voluntarily signed the informed consent form, communicated well with the investigator, and completed all visits as required by the protocol.

Exclusion Criteria:

Subjects with other autoimmune diseases that the investigator considers would not potentially benefit from A-319 treatment; or conditions that interfere with the assessment of joint swelling and pain. 2. Use of abatacept, infliximab, adalimumab, or tocilizumab within 6 weeks prior to the first treatment with the study drug; use of etanercept, anakinra, immune globulin, or blood products within 4 weeks prior to the first treatment with the study drug; or use of a JAK inhibitor (e.g., tofacitinib, baricitinib, or upadacitinib), mycophenolate mofetil, cyclosporine, or iguratimod within 2 weeks prior to the first treatment with the study drug.

3. Use of B-cell depleting therapy, such as rituximab, within 3 months prior to the first treatment with the study drug; cell counts must have returned to acceptable levels or baseline.

4. Subjects with any periprosthetic joint infection. 5. Patients with immunodeficiency (defined as immunoglobulin G ≤ 5g/L). 6. History of demyelinating diseases, including, but not limited to, multiple sclerosis, Guillain-Barré syndrome, and neuromyelitis optica (Devic's disease). 7. Laboratory values: Hemoglobin level < 9.0 g/dL, absolute white blood cell (WBC) count < 3.0 × 109/L (< 3000/mm3), or absolute neutrophil count < 1.2 × 109/L (< 1200/mm3), or absolute lymphocyte count < 0.8 × 109/L (< 800/mm3); thrombocytopenia, defined as a platelet count < 100 × 109/L (< 100,000/mm3); age-appropriate estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2, proteinuria ≥ 3+; total bilirubin (T-bili), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) exceeding 1.5 times the upper limit of normal (ULN). 8. Receipt of live or live attenuated vaccines within 30 days prior to first medication use.

9. Active hepatitis during the screening period, or positive hepatitis B virus surface antigen (HBsAg), or positive hepatitis B virus core antibody (HBcAb) plus hepatitis B virus (HBV) deoxyribonucleic acid (DNA), or positive hepatitis C virus (HCV) antibody plus HCV RNA; history of human immunodeficiency virus (HIV) infection, or positive HIV antibody during the screening period; or positive Treponema pallidum antibody during the screening period.

10. Chronic active infection or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks prior to screening, or superficial skin infection requiring treatment within 1 week prior to screening (Note: Patients can be rescreened after the infection is resolved). 11. Major surgical procedure (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures within 4 weeks prior to the first dose of study drug, or plans for major surgery during the study.

12. A history of a major clinical illness (such as circulatory system disorders, endocrine system disorders, nervous system diseases, respiratory system diseases, hematologic diseases, immune system diseases, psychiatric disorders, and metabolic instability) that the investigator believes will pose a risk to the patient's safety, or that may affect safety or efficacy analysis if the disease/symptom worsens during the study. For example: Cardiovascular disease: history of acute myocardial infarction, unstable angina, or severe arrhythmias (multi-source frequent premature ventricular contractions, ventricular tachycardia, or ventricular fibrillation) within 6 months prior to screening; New York Heart Association (NYHA) class III-IV.

13. Possible active Mycobacterium tuberculosis infection, defined as: positive sputum smear/sputum culture within 3 months prior to screening/during the screening period, or chest X-ray (anteroposterior and lateral)/lung CT indicating active tuberculosis infection (tuberculosis testing will be performed according to the site's protocol if ethically required).

14. Subjects with a malignancy within 5 years prior to screening (excluding completely cured in situ cervical cancer, non-metastatic squamous cell carcinoma or basal cell carcinoma of the skin, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma).

15. History of major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/or bone marrow transplant).

16. Participation in any clinical trial within 4 weeks prior to the first dose of study drug or within 5 half-lives of the study drug in the clinical trial (whichever is longer, unless otherwise specified).

17. Patients undergoing acute or consolidation medication for depression and experiencing suicidal thoughts within 6 months. 18. Women who are pregnant or breastfeeding, or who plan to become pregnant or breastfeed during the study; or men whose partners plan to become pregnant during the study.

19. Any reason that the researcher deems would prevent the subject from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A-319 subcutaneous intervention; A-319 will be administered subcutaneously in two ascending dose levels: Dose A and Dose B, with a total treatment course of 4 weeks. Expected enrollment: Dose A, B: 3+N; Total: 12-18 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)	Time frame: Within 1 year after subcutaneous injection of A-319

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of A-319	Blood samples were collected from the sampling points according to the plan, and the concentration of A-319 in the patients' serum was measured and the pharmacokinetic parameters were calculated	Within 1 month after subcutaneous injection of A-319
Numbers of Participants with positive antidrug antibodies in peripheral blood	To evaluate immunogenicity of A-319	Before dosing on day 1, before dosing on day 15, on days 28-29, and at weeks 8, 16, and 24
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 after subcutaneous injection of A-319
Pharmacodynamics of A-319	Pharmacodynamics will be assessed by levels of lymphocyte subsets in peripheral blood	Within 1 month after subcutaneous injection of A-319

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
68 swollen joints and 66 tender joints assessed	68 swollen joints and 66 tender joints were assessed by independent joint assessors and reviewed by safety assessors.	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Physician's Global Assessment of Disease (PhGADA-VAS)	The PhGADA_VAS is a component of the ACR evaluation and is used to assess treatment efficacy. The PhGADA_VAS uses a visual analog scale (0-100 mm, with 0 indicating no disease activity and 100 indicating very severe disease activity) to assess a patient's current disease activity.	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Disease activity score based on C-reactive protein (DAS28-CRP)	The DAS28-CRP score includes the following: swollen joints, tender joints, CRP, PhGADA_VAS	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Disease activity score based on erythrocyte sedimentation rate (DAS28-ESR)	The DAS28-ESR score includes the following: swollen joints, tender joints, ESR, PhGADA_VAS swelling degree, and pain degree.	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
American College of Rheumatology criteria 20, 50, and 70 (ACR20, ACR50, ACR70)	ACR20 is defined as an improvement of at least 20% in the ACR score. ACR50 and ACR70 are defined as improvements of at least 50% and 70% in the ACR score. That is, an improvement of at least 20%, 50%, and 70%	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Patient Global Assessment of Disease (PhGA-VAS)	PhGA_VAS is a component of the ACR evaluation and is used to assess efficacy.The PhGA_VAS assesses the patient's overall assessment of their current illness using a visual analog scale (0-100 mm, with 0 indicating very good and 100 indicating very poor). It asks the patient how they feel about their current illness.	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Patient's global assessment of joint pain (VAS)	The patient's global assessment of joint pain (VAS) is a component of the ACR evaluation and is also used to assess efficacy. PhGADA_VA has only a single question, which asks patients, "How severe is the joint pain caused by rheumatoid arthritis?" The assessment is done using a visual analog scale (0-100 mm, with 0 indicating no pain and 100 indicating the worst pain).	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Health Assessment Questionnaire-Disability Index (HAQ-DI)	The Health Assessment Questionnaire-Disability Index (HAQ-DI) is a component of the ACR evaluation and is also used to assess treatment efficacy. The HAQ-DI is a patient questionnaire assessing RA-related disability (physical function assessment). It consists of 20 questions across eight dimensions. Scaled on a 0-3 scale, 0 = no difficulty, 1 = some difficulty, 2 = very difficult, and 3 = unable to complete.	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Simple Disease Activity Index (SDAI)	The Simple Disease Activity Index (SDAI) is a tool for assessing disease activity that integrates physical examination, acute reaction substances, patient reports, and physician assessments. It includes the following: swollen joints (0-28), tender joints (0-28), CRP (0.1-10 mg/dL), PaGA (0-100 mm), and PhGADA (0-100 mm).	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)
Clinical Disease Activity Index (CDAI)	The Clinical Disease Activity Index (CDAI) is similar to the SDAI. This scale does not include laboratory tests and can be assessed immediately. The CDAI includes the following: swollen joints (0-28), tender joints (0-28), PaGA (0-100 mm), and PhGADA (0-100 mm).	A-319 within 1 year after subcutaneous injection (Day 15, Day 28, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12)

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Collaborators: ITabMed Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: August 19, 2025
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis (RA); A-319
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: UHCT250824

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