CD19 CAR-T in the Treatment of Relapsed/Refractory Autoimmune Diseases

Recruiting now · Early Phase 1

Conditions studied: Autoimmune Diseases

In brief

Autoimmune diseases such as systemic lupus erythematosus (SLE), diffuse cutaneous systemic sclerosis (dcSSc), antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV), idiopathic inflammatory myopathy (IIM), and Sjogren's syndrome (SS) have complex etiologies and are prone to cause systemic multiple organ damage. Because patients need lifelong medication due to repeated disease recurrence, and the current treatment of the above autoimmune diseases has limited efficacy and greater side effects, so that patients bear an excessive burden of disease, therefore, there is an urgent need to explore safer and more effective treatment. Several autologous CAR-T products targeting CD19 have been marketed for the treatment of B-cell hematological malignancies. Depletion of B cells to suppress abnormal immune responses is also currently one of the popular strategies for the treatment of antibody-mediated autoimmune diseases, and many clinical studies of CAR-T against autoimmune diseases are still ongoing. Therefore, a dose escalation trial is planned to evaluate the safety, tolerability, and preliminary efficacy of autologous CD19 CAR-T in patients with relapsed/refractory autoimmune diseases.

Key facts

Study ID

NCT06680388

Run by

Institute of Hematology & Blood Diseases Hospital, China

People needed

15

Starts

2024-11-15

Expected to finish

2027-12-31

Last updated by the study team

2025-12-24

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 1、aged 18 to 65 years (including 18 and 65 years), male or female;
• 2、Special criteria for different indications:
• 2.1 Subjects with relapsed/refractory moderate to severe SLE must meet the following criteria:
• 1) diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE;
• 2) positive antinuclear antibody (ANA) (titer ≥ 1:80), and/or positive anti-dsDNA -antibody, and/or positive anti-Sm antibody at screening;
• 3) moderate to severe activity is defined as: SLEDAI-2000 ≥ 8 points at screening; if there is a score of low complement and/or anti-dsDNA antibody, the score for clinical symptoms of SLEDAI-2000 (except low complement and/or anti-ds-DNA antibody) needs to be ≥ 6 points;
• 4) stable standard treatment regimen for at least 6 months in the history of SLE before screening, and the disease remains active for at least 2 months before screening. Standard treatment regimen refers to stable use of any of the following drugs (alone or in combination): glucocorticoids (≤ 20 mg/day prednisone or equivalent), antimalarials (hydroxychloroquine ≤ 400 mg/day, chloroquine ≤ 500 mg/day), non-steroidal anti-inflammatory drugs (NSAIDs), biologics (rituximab, belimumab, tatacept) and other immunosuppressive agents or immunomodulators, including mycophenolate mofetil (≤ 2 g/day), azathioprine (≤ 2 mg/kg/day), methotrexate (≤ 20 mg/week);
• 2.2 Subjects with relapsed/refractory dcSSc were required to meet the following criteria:
• 1) diagnosis of SSc according to the 2013 EULAR/ACR classification criteria for systemic sclerosis (SSc);
• 2) diffuse cutaneous manifestations according to the 1988 LeRoy et al criteria, ie, extensive skin fibrosis with proximal elbow and/or knee skin involvement;
• 3) interstitial lung disease (ILD) at screening, and 45% predicted ≤ forced vital capacity (FVC) ≤ 70% predicted, or 40% predicted ≤ diffusing capacity for carbon monoxide (DLCO) ≤ 70% predicted;
• 4) relapse/refractory was defined as failure to respond to prior conventional therapy or relapse after disease remission. Conventional therapy was defined as the use of corticosteroids, cyclophosphamide, and at least 1 immunosuppressive/modifying agent for ≥ 6 months, including azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, rituximab, belimumab, and taitacept;
• 5) activity was defined as having at least 1 of the following: evidence of skin progression at screening, ie, an increase in mRSS score of ≥ 10% within the past 6 months; evidence of any of the following ILD activities at screening: newly diagnosed ILD within the past 6 months; decline in FVC of 10%, or decline in FVC of 5% with DLCO of 15% within the past 6 months in subjects with preexisting ILD.
• 2.3 Subjects with/refractory AAV must meet the following criteria:
• 1) a clinical diagnosis of granulomatous vasculitis (GPA) and microscopic polyangiitis (MPA) as defined by the 2012 Chapel Hill Consensus Conference (CHCC);
• 2) at least one major item or at least three other items in Birmingham Vasculitis Activity Score (BVAS) version 3;
• 3) positive antiproteinase-3 (PR3-ANCA) antibody or antimyeloperoxidase (MPO-ANCA) antibody at screening;
• 4) relapsed/refractory as defined by: Subjects with relapsed AAV: initial response to prior treatment with corticosteroids combined with immunosuppressive agents (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) for at least 3 months (BVAS score 0 and glucocorticoid dose ≤ 7.5 mg/day prednisone or other equivalent glucocorticoid agents) or 1 - 2 additional items emerging in two consecutive assessments),Patients with relapsed disease within 12 weeks before screening; subjects with refractory AAV: those who had not achieved response after at least 3 months of previous treatment with glucocorticoids combined with immunosuppressive agents (cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate mofetil, etc.) (BVAS score of 0 and glucocorticoid dose ≤ 7.5 mg/d prednisone or other equivalent glucocorticoid drugs);
• 2.4 Subjects with relapsed/refractory IIM were required to meet the following criteria:
• 1) have a ≥ 55% probability of being diagnosed with IIM according to the 2017 EULAR/ACR classification criteria for IIM, and were classified as having dermatomyositis (DM), polymyositis (PM), or immune-mediated necrotizing myopathy (IMNM) based on age at first onset, skin and muscle strength performance, laboratory tests, and muscle biopsy characteristics:；
• 2) disease activity/severity meeting the following criteria: free-hand muscle strength test-8 (MMT-8) score ≤ 141 (total score 150)；meet at least 2 of the other CSMs abnormalities: overall disease activity assessed by the patient [based on visual analogue scale (VAS)] score ≥ 2 points (range 0 - 10 points); overall disease activity VAS score ≥ 2 points (range 0 - 10 points) assessed by the physician; VAS score ≥ 2 points (range 0 - 10 points) for extramuscular overall disease activity assessed by the physician; Physician assessed health assessment questionnaire disability index (HAQ-DI) score ≥ 0.25 (range 0-3). At least 1 muscle enzyme level > 1.5 times the upper limit of normal (ULN).
• 2.5 Subjects with relapsed/refractory SS were required to meet the following criteria:
• 1) diagnosis of SS according to the 2016 EULAR/ACR classification criteria for SS;
• 2) anti-Ro/SSA antibody positivity at screening;
• 3) dynamic total salivary flow rate ≥ 0.05 mL/min or static total salivary flow rate ≥ 0.01 mL/min at screening;

Where it is running

• Chinese Academy of Medical Sciences Hospital of Hematology (Chinese Academy of Medical Sciences Institute of Hematology), Tianjin, 300020 — Tianjin, Tianjin Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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