CAR-T cell therapy for patients with systemic lupus erythematosus

A Safety, Efficacy, and Pharmacokinetics Study of Anti-CD19 CAR-T Cell Therapy in Participants With Moderate to Severe Active Systemic Lupus Erythematosus

This study is testing a new CAR-T cell therapy to see if it can help people with moderate to severe systemic lupus erythematosus feel better.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Wuhan Union Hospital, China (Academic / other)
• Drugs / interventions: chemotherapy, Prednisone
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06310811 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of RD06-04, a CAR-T cell therapy, in patients with moderate to severe active systemic lupus erythematosus (SLE). The study uses a dose escalation approach, enrolling patients in two dose levels to assess safety and treatment response. A total of 12 patients will be treated, with the possibility of expanding the cohort based on initial safety findings. The trial aims to provide insights into the pharmacokinetics and pharmacodynamics of the therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a confirmed diagnosis of systemic lupus erythematosus who have not responded adequately to standard treatments.

Not a fit: Patients who have not been treated with glucocorticoids and immunosuppressants or those with mild SLE may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a new treatment option for patients suffering from severe systemic lupus erythematosus.

How similar studies have performed: While CAR-T cell therapies have shown promise in other conditions, this specific application for systemic lupus erythematosus is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* 1.The subjects voluntarily participated in the experiment and signed the informed consent.

  2. Age ≥18 years old and ≤70 years old, regardless of gender. 3. Diagnosis of SLE according to the European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria 2019 or the 2012 International Clinical Collaboration Group on Systemic Erythraeus (SLICC) criteria.

  4. Prior to screening, patients must have been treated with glucocorticoids combined with immunosuppressants and/or biologics for at least 2 months, and the dose is stable for \>2 weeks, and the disease is still active (i.e., previous treatment with glucocorticoids + immunosuppressants or glucocorticoids + immunosuppressants + biologics, and any of the above drugs are not eligible for single drug use). Oral corticosteroids must meet the following requirements: 1) Prednisone (or equivalent) ≥7.5mg/ day; 2) There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants and/or biologics.

  5. Screening is positive for antinuclear antibody (ANA), and/or anti-DS-DNA antibody, and/or anti-Smith antibody.

  6. The SLEDAI-2K score in the screening period was \>6, and the "clinical" SLEDAI-2K score was ≥4.

Note: "Clinical" SLEDAI-2K is a score in the SLEDAI-2K score that does not include results attributable to any urine or laboratory tests (including immunological indicators) :

7. The BILAG2004 score meets at least one of the following conditions:

a) ≥1 organ system BILAG2004 Class A disease b) ≥2 organ systems BILAG2004 Class B disease 8. Physician General assessment (PGA) score ≥1.0 (0-3 on visual analogue scale VAS) during screening.

9. Organ function and laboratory tests:

1. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST≤3× upper normal limit (ULN), total bilirubin (TBIL) ≤2×ULN (except Gilbert syndrome).
2. Renal function: creatinine ≤1.5×ULN or creatinine clearance ≥40 ml/min.
3. Blood routine: neutrophil count ≥1×109/L, hemoglobin ≥60g/L, platelet count ≥20×109/L, lymphocyte count \>0.3×109/L.
4. Coagulation function: International standardized ratio (INR) ≤ 1.5×ULN, or prothrombin time (PT) ≤ 1.5×ULN.
5. Blood oxygen saturation (SpO2) at rest in indoor air ≥92%.
6. Echocardiography showed left ventricular ejection fraction (LVEF) ≥50%. 10. The serum or urine pregnancy test results of fertile female subjects at the time of screening were negative.

   11. Fertile women must consent to the use of highly effective contraceptive methods for contraception from at least 28 days before the start of the infusion until 12 months after the RD06-04 reinfusion. Fertile men must consent to the use of an effective barrier method of contraception from the start of DTP until 12 months after RD06-04 reinfusion, and should not donate semen or sperm throughout the trial period.

   Exclusion Criteria:
   * 1. Combined with other autoimmune diseases, systemic treatment is required. 2. The presence of uncontrolled lupus crises within 8 weeks prior to screening, including acute lupus nephritis, severe neuropsychiatric lupus, severe hemolytic anemia, severe immune thrombocytopenia, agranulophilia, severe heart damage, severe lupus pneumonia, severe lupus hepatitis, and severe vasculitis, was assessed by the investigators as not suitable for participation in this study.

     3. Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, cerebral organ syndrome, or psychosis.

     4. Have a history of allogeneic bone marrow or stem cell transplantation or solid organ transplantation (such as kidney, lung, heart, liver) or plan to undergo such transplantation in the future.

     5. Clinically significant cardiovascular dysfunction in the 12 months prior to screening, including but not limited to: Class III or IV heart failure as defined by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, or any ventricular arrhythmias.

     6. A history of malignant neoplasm within 5 years prior to signing the ICF, with the exception of sufficiently treated or surgically resected non-melanoma skin cancer or carcinoma in situ (e.g. cervical, bladder, breast) with no residual disease.

     7. Pregnant or lactating women. 8. A history of recurrent infections requiring hospitalization and intravenous antibiotics (e.g., 3 or more infections of the same type in the past year).

     9. There are active infections, such as infectious pneumonia and tuberculosis, that need systematic treatment within 2 weeks before the treatment.

     10. Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA test positive; Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive.

     11. Have received live attenuated vaccine within 4 weeks prior to treatment or plan to receive live attenuated vaccine during the course of the study.

     12. Receiving high doses of corticosteroids (prednisone ≥60 mg/ day or equivalent) within 4 weeks prior to drenching, or failing to taper prednisone to ≤10 mg/ day 5 days prior to drenching.

     13. As indicated in Table 3, tapering or elution of background therapy is not possible prior to eluvial chemotherapy.

     14. Were receiving renal replacement therapy in the 3 months prior to screening or expected to require renal replacement therapy during the study period.

     15. History of drug or alcohol abuse within 1 year prior to screening. 16. History or evidence of suicidal thoughts in the 6 months prior to screening, or any suicidal behavior in the 12 months prior to screening, is considered by the investigator to be a significant risk of suicide.

     17. Use of other study drugs within 4 weeks or 5 half-lives (whichever is older) prior to screening.

     18. A history of hypersensitivity or life-threatening reactions to any ingredient or preparation of an investigational drug or investigational treatment, including chemotherapy. For more information about the ingredients of the investigational drug, see the Investigator's Manual (IB).

     19. Any situation that the investigator believes may affect study participation, pose a safety risk to patients, or may confuse the interpretation of study results.

Where this trial is running

Wuhan, Hubei

• Wuhan Union — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Heng Mei, Chief physician

Conditions Safety; Effective; CD19 CART, SLE