Safety and Efficacy of SWK002 in Patients with D2T-Rheumatoid Arthritis

This is an open label, single-site, dose-escalation study in up to 18 participants with refractory rheumatoid arthritis. This study aims to evaluate the safety and efficacy of the treatment with Anti-CD19 CART.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Anti-CD19 CART cells will be given IV at split doses.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhu Chen Professor of medicine, M.D.; Phone Number: 860551-62283843; Email: doczchen@gmail.com
• Study Contact Backup: Name: Zhu Chen Professor, M.D.; Phone Number: 860551-62283843; Email: doczchen@gmail.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410119
      • Recruiting
      • Hunan Siweikang Therapeutic Co.Ltd
      • Contact: Zhu Chen Professor, M.D.; Phone Number: 800-555-5555; Email: doczchen@ustc.edu.cn
      • Contact: Zhu Chen Professor
      • Contact: Xingbing Wang Professor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. no gender restriction and age of 18 years and above at the time of signing the informed consent form.
2. written informed consent approved by the Ethics Committee must be signed in person by all subjects or guardians prior to the commencement of any screening procedure.
3. adult refractory patients who meet the 2010 ACR / EULAR RA diagnostic criteria, with refractory defined as (1) failure of treatment with csDMARDs (2) experiencing failure of treatment with ≥2 bDMARDs/tsDMARDs with different mechanisms of action (3) meeting one of the following criteria: 1) DAS28-ESR >3.2 or CDAI >10 2) inability to hormone Hormone cannot be reduced to less than 7.5mg/day (3) Number of swollen joints and/or painful joints ≥3.
4. Stable treatment with 1 or 2 cs DMARD ( s ) prior to enrollment as follows: (1) at least 12 weeks of methotrexate and at least 4 weeks of administration at a dose of 7.5-25 mg/week (2) at least 4 weeks of stable hydroxychloroquine dose of ≤400 mg/d (3) at least 4 weeks of stable oral salicylsulphadiazepine 1-3 g/d (4) at least 4 weeks of stable oral leflunomide 10-20 mg/day Methylphenidate 10-20 mg/d.
5. no active or latent tuberculosis.
6. Adequate organ function: (1) blood creatinine ≤1.5 times the upper limit of normal, or glomerular filtration rate (eGFR) ≥60m/min/1.73m2 as estimated by the MDRD formula (2) and ALT ≤ 5 times the upper limit of normal for the corresponding age and total bilirubin ≤ 2.0 mg/dl (3) and ≤ 1 grade of dyspnea and oxygen saturation > 91% in room air.
7. hemodynamically stable with a left ventricular ejection fraction (LVEF) ≥45% as determined by echocardiography or multichannel radionuclide angiography (MUGA).
8. female subjects of childbearing potential and all male subjects must agree to use a highly effective method of contraception until at least 12 months after SWK002 infusion and until two consecutive PCR assays show no more CAR-T cells in the body.

Exclusion Criteria:

1. malignant tumors.
2. subjects with current or history of CNS disorders such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
3. previous subjects who have undergone allogeneic hematopoietic stem cell transplantation (HSCT).
4. subjects who have received chemotherapy other than pretreatment chemotherapy within 2 weeks prior to infusion.
5. subjects who have received other investigational drug therapy within 30 days prior to signing the informed consent.
6. active hepatitis B (defined as hepatitis B surface antigen positivity or hepatitis B core antibody positivity combined with a hepatitis B virus DNA test value >1000 copies/ml) or hepatitis C (HCV RNA positivity) subjects.
7. HIV antibody positive or syphilis spirochete antibody positive subjects.
8. subjects with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g., positive blood cultures ≤ 72 hours prior to infusion).
9. subjects who have lost or donated more than 400 mL of blood within 2 months prior to screening or have received a blood transfusion.
10. any history of definite drug or food allergy, especially to drugs related to the therapeutic agents (e.g., fludarabine, cyclophosphamide) or product components (e.g., DMSO) used in this trial.
11. any systemic cytotoxic or systemic immunosuppressive agent within 6 months prior to screening or during the study period, or any localized cytotoxic or localized immunosuppressive agent within 30 days or 5 half-lives (whichever is longer) prior to screening or during the study period.
12. pregnancy (as determined by blood pregnancy test) or lactation.
13. prevalence of systemic inflammatory diseases other than RA (except secondary Sjogren's syndrome), including but not limited to juvenile chronic arthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis, systemic lupus erythematosus, ankylosing spondylitis, reactive arthropathy, systemic vasculitis, or gout.
14. the existence of unstable angina pectoris and/or myocardial infarction in the 6 months prior to signing the informed consent.
15. other conditions that, in the opinion of the investigator, should not be enrolled in this clinical study, such as poor compliance.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-CD19 CART; Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of Anti-CD19 CART will be infused on day 0.	Drug: Anti-CD19 CART cells will be given IV at split doses.; Split intravenous infusion of Anti-CD19 CART cells of (Dose escalating infusion of 1 - 6 x10^6 CART cells/kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcome	All adverse events (AEs) will be listed and summarized. Summaries of laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the All Treated analysis set.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The persistence, accumulation, and migration of Anti-CD19 CART cells	Assessing the trafficking of Anti-CD19 CART cells in the peripheral blood at the time of each infusion as well as at each time of follow-up by Quantitative Real-time Polymerase Chain Reaction or flow cytometry. Peripheral blood will be collected prior to the initial infusion and will be set as baseline.	Day-1, 1, 3, 5, 7, 9, 11, 14, 21, 28 and Month 2, 3, 6, 9, 12
Erythrocyte Sedimentation Rate	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
American College of Rheumatology (ACR) criteria 20, 50, 70 response rate	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
Swollen and tender joint count	To evaluate RA disease activity	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
Visual Analogue Scale	The visual analogue scale is used to assess pain. The basic method is to use a swimming scale about 10cm long, marked with 10 scales on one side, and the two ends are "0" and "10" respectively, 0 points represent no pain, and 10 points represent the most unbearable pain.	Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: July 7, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: SWKCART23071101

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