Targeted CAR-T therapy for autoimmune diseases

Clinical Study on Targeted CD19/BCMA CAR-T Therapy for Autoimmune Diseases

This study is testing a new CAR-T cell therapy to see if it can help people with autoimmune diseases like lupus, scleroderma, and multiple sclerosis feel better.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Nanjing Bioheng Biotech Co., Ltd. (industry)
• Locations: 1 site (Lianyungang, Jiangus)
• Trial ID: NCT06775912 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and effectiveness of RD06-05, a targeted CAR-T cell therapy, in patients with various autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and multiple sclerosis (MS). The study is designed to assess pharmacokinetics, pharmacodynamics, and tolerability of the treatment. Participants will receive CAR-T cell injections and will be monitored for their response and any adverse effects. The trial aims to provide insights into a novel therapeutic approach for managing these challenging conditions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with active autoimmune diseases such as SLE, SSc, IIM, NMOSD, or MS.

Not a fit: Patients with significant organ dysfunction or those outside the specified age range 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 autoimmune diseases.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, their application in autoimmune diseases is still novel and largely untested.

Eligibility criteria

Inclusion Criteria:

1. The subjects voluntarily participated in the study and signed the informed consent form.
2. Age ≥18 years old and ≤70 years old, both sexes.
3. Organ function and laboratory tests:

   1. Liver function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN), total bilirubin (TBIL) ≤2×ULN (except Gilbert's 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: international normalized ratio (INR) ≤ 1.5×ULN, or prothrombin time (PT) ≤ 1.5×ULN.
   5. Oxygen saturation (SpO2) ≥92% at rest in room air.
   6. Left ventricular ejection fraction (LVEF) ≥50% on echocardiography.
4. Negative serum or urine pregnancy test results in female subjects of childbearing potential at screening.
5. Women of childbearing potential must agree to use a highly effective method of contraception for at least 28 days before initiation of elution and up to 12 months after RD06-04 reinfusion. Men of childbearing potential had to agree to the use of an effective barrier method of contraception from the initiation of lymphoidectomy until 12 months after reinfusion of RD06-04 and had to refrain from donating semen or sperm throughout the trial.

SLE Patient Inclusion Criteria:

1. A definitive diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria.
2. Positive antinuclear antibodies (ANA) at screening, and/or positive anti-double-stranded DNA (anti-dsDNA) antibodies, and/or positive anti-Smith antibodies.
3. A SLEDAI-2K score \>6 at screening, and a 'clinical' SLEDAI-2K score ≥4.

SSc Patient Inclusion Criteria:

1. Diagnosed with SSc according to the 2013 ACR/EULAR classification criteria.
2. Diagnosed with diffuse cutaneous SSc at screening, with a disease duration ≤6 years.

AAV Patient Inclusion Criteria:

1. Meeting the diagnostic criteria for ANCA-associated vasculitis established by the 2022 ACR/EULAR, including Microscopic Polyangiitis (MPA), Granulomatosis with Polyangiitis (GPA), and Eosinophilic Granulomatosis with Polyangiitis (EGPA).
2. Positive testing for ANCA-associated antibodies 3 months before screening or at screening (specifically, positive anti-myeloperoxidase antibodies, MPO-ANCA, or positive anti-proteinase 3 antibodies, PR3-ANCA).

IIM Patients Inclusion Criteria:

1. Diagnosed with IIM according to the 2017 ACR/EULAR classification criteria (including probable or definite diagnosis, i.e., probability ≥55%), including subtypes such as Dermatomyositis (DM), Anti-Synthetase Syndrome (ASS), and Immune-Mediated Necrotizing Myopathy (IMNM).
2. Patients in the active phase, defined as those with at least 2 of the following six core set measures being abnormal: decreased muscle strength (MMT-8 \<142), Physician Global Assessment (PhGA, 10cm VAS) ≥2cm, Patient Global Assessment (PtGA, 10cm VAS) ≥2cm, Extramuscular Disease Activity Total Score (assessed using the MDAAT scoring tool) ≥2cm, Health Assessment Questionnaire (HAQ) ≥0.25, and Creatine Kinase (CK) muscle enzyme levels ≥1.5×ULN

Sjögren's Syndrome (SS) Patient Inclusion Criteria:

1. Diagnosed with primary Sjögren's Syndrome according to the 2016 ACR/EULAR classification criteria.
2. Positive for anti-SSA/Ro antibodies detected 3 months before screening or at screening.
3. A score of ≥5 on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) at screening.

Exclusion Criteria:

1. SLE Patients: Those with uncontrolled lupus crisis within the 8 weeks prior to screening, including rapidly progressive lupus nephritis, severe neuropsychiatric lupus, severe hemolytic anemia, severe immune thrombocytopenia, agranulocytosis, severe cardiac damage, severe lupus pneumonia, severe lupus hepatitis, and severe vasculitis, as assessed by the investigator as unsuitable to participate in this study.
2. IIM Patients: Presence of severe rhabdomyolysis or CK levels ≥120×ULN at screening.
3. Patients with severe asthma or Chronic Obstructive Pulmonary Disease (COPD) are eligible. Patients with mild or moderate asthma or COPD who are receiving stable treatment can also be enrolled.
4. There has been an active infection requiring systemic treatment within 2 weeks prior to the urethral irrigation, such as infectious pneumonia, tuberculosis, etc.
5. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive for hepatitis C virus (HCV) antibody with detectable HCV RNA in peripheral blood; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis antibody.
6. Pregnant or breastfeeding women.
7. Any condition that, in the investigator's opinion, may affect study participation, pose a safety risk to the patient, or potentially confound the interpretation of study results.

Where this trial is running

Lianyungang, Jiangus

• The First People's Hospital of Lianyungang — Lianyungang, Jiangus, China (RECRUITING)

Study contacts

• Study coordinator: Xiao Shi

Conditions: SLE, Systemic Sclerosis, IIM, NMOSD, MS, MG, ANCA Associated Vasculitis