Clinical trial NCT06503237: Safety and Efficacy of SWK002 in Patients With D2T-Rheumatoid Arthritis
Official title: Safety and Efficacy of SWK002 in Patients With D2T-Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rheumatoid Arthritis
Lead sponsor: The First Affiliated Hospital of University of Science and Technology of China
Sponsor class: OTHER
First posted: 2024-07-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 \&gt;3.2 or CDAI \&gt;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 \&gt; 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 \&gt;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\&#39;s syndrome), including but not limited to juvenile chronic arthritis, Crohn\&#39;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.

Primary outcomes:
measure: Safety Outcome
timeFrame: up to 2 years
Secondary outcomes:
measure: The persistence, accumulation, and migration of Anti-CD19 CART cells
timeFrame: Day-1, 1, 3, 5, 7, 9, 11, 14, 21, 28 and Month 2, 3, 6, 9, 12
measure: Erythrocyte Sedimentation Rate
timeFrame: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
measure: American College of Rheumatology (ACR) criteria 20, 50, 70 response rate
timeFrame: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
measure: Swollen and tender joint count
timeFrame: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
measure: Visual Analogue Scale
timeFrame: Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Siweikang Therapeutic Co.Ltd
state: Hunan
Study officials:
References: