Clinical Study on the Targeted CD19 Universal CAR-T Cell Injection (RD06-04) for the Treatment of IIM and AAV

Официальное название

Clinical Study on the Safety, Efficacy, and Pharmacokinetics of a Universal CD19-Targeted CAR-T Cell Injection (RD06-04) in the Treatment of Patients With Refractory Inflammatory Myopathy and ANCA-Associated Vasculitis

Обзор

This is an open-label, investigator-initiated clinical trial (IIT) designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of RD06-04 in patients with refractory IIM and AAV. The study plans to enroll a total of 12 participants, with 6 cases each for IIM and AAV. Enrollment for both diseases will proceed in parallel. The dose will be 6×10\^6 CAR+T cells/kg (±30%), and patients will receive a single infusion of RD06-04.

Вмешательства

• Препарат RD06-04 Cell Injection Infusion
  CAR T-cell therapy administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Первичные конечные точки

• Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI) [Срок оценки: Up to 2 years]

Вторичные конечные точки (9)

• The proportion of patients with kidney involvement achieving complete kidney remission (CRR) [Срок оценки: At weeks 12, and months 6, 12, 18, and 24 following CAR-T infusion.]
• The change in UPCR from baseline in patients with kidney involvement. [Срок оценки: At weeks 2, 4, 8, 12, and at months 6, 9, 12, 18, and 24 following CAR-T infusion.]
• The change in eGFR (estimated glomerular filtration rate) from baseline in patients with kidney involvement. [Срок оценки: At weeks 2, 4, 8, 12, and at months 6, 9, 12, 18, and 24 following CAR-T infusion.]
• The change in BVAS score from baseline in AAV patients [Срок оценки: At 6, 12, 18, and 24 months following CAR-T infusion.]
• IIM patients were assessed for major clinical remission (Total Improvement Score, TIS) according to the 2016 ACR /EULAR criteria for myocarditis remission. [Срок оценки: At 6, 12, 18, and 24 months following CAR-T infusion.]
• The change in FACIT-Fatigue from baseline. [Срок оценки: At 6, 12, 18, and 24 months following CAR-T infusion.]
• Assessment of the peak amplification level (Cmax), area under the concentration-time curve (AUC0-28), and persistence profile of RD06-04. [Срок оценки: Up to 2 years]
• The change in HAQ-DI from baseline. [Срок оценки: At 6, 12, 18, and 24 months following CAR-T infusion.]
• Assessment of the incidence and titer levels of anti-RD06-04 specific anti-drug antibodies (ADA). [Срок оценки: Up to 2 years]

Критерии участия

General Inclusion Criteria:

• The subject voluntarily participates in this trial and has signed the informed consent form.
• Age ≥18 years and ≤70 years, regardless of gender.
• Organ Function and Laboratory Tests:

• Liver Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN), total bilirubin (TBIL) ≤2×ULN (except for Gilbert syndrome).
• Renal Function: Creatinine ≤1.5×ULN or creatinine clearance ≥40 ml/min.
• Blood Routine: Neutrophil count ≥1×10\^9/L, hemoglobin ≥60 g/L, platelet count ≥50×10\^9/L, lymphocyte count >0.3×10\^9/L.
• Coagulation Function: International normalized ratio (INR) ≤1.5×ULN, or prothrombin time (PT) ≤1.5×ULN.
• Oxygen saturation (SpO2) ≥92% at rest while breathing room air.
• Echocardiography shows left ventricular ejection fraction (LVEF) ≥50%.
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test result during screening.
• Females of childbearing potential must agree to use highly effective contraception from at least 28 days before the start of lymphodepletion until 12 months after the infusion of RD06-04. Males of reproductive potential must agree to use an effective barrier method of contraception from the start of lymphodepletion until 12 months after the infusion of RD06-04 and must not donate semen or sperm during the entire trial period.

For IIM participants:

1\. Diagnosed with IIM (including probable or definite diagnosis, i.e., a probability of ≥55%) according to the 2017 ACR/EULAR classification criteria. Currently, the ENMC considers that the subtypes of IIM mainly include dermatomyositis (DM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM).

For AAV participants:

1\. Meets the diagnostic criteria for ANCA-associated vasculitis as established by the 2022 ACR/EULAR, including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA).

Критерии исключения

• As determined by the investigator, the primary diagnosis is a rheumatic autoimmune disease other than the disease under study, which the investigator believes may confound the efficacy evaluation of the study disease.
• Clinically significant central nervous system disease or pathological changes not caused by the non-study disease within 12 months prior to screening.
• History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation (such as kidney, lung, heart, liver) or plans for such transplantation in the future.
• For IIM patients: Presence of severe rhabdomyolysis or CK levels ≥120×ULN at screening.
• History of, or current significant cardiovascular dysfunction.
• History of malignancy within 5 years prior to signing the ICF.
• Pregnant or breastfeeding women.
• History of recurrent infections requiring hospitalization and intravenous antibiotics (e.g., three or more episodes of the same type of infection within the past year).
• 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.
• History of drug or alcohol abuse within 1 year prior to screening.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University People's Hospital — Пекин

Идентификаторы

NCT: NCT06986018 · BHCT-RD06-04-08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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