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

NCT06680388 | Recruiting Early Phase 1

• 1 other identifier: IIT2024072
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autoimmune Diseases

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT);

  • Grade ≥ III acute GvHD that has not resolved to Grade I or II within 7 days, with the exception of acute GvHD with skin involvement only; • Grade ≥ 4 CRS, or Grade 3 CRS that has not resolved to Grade 1 or 2 within 14 days of onset; • Grade 4 ICANS or Grade 3 ICANS lasting ≥ 7 days; • Other Grade 3 or higher AEs associated with autologous CD19 CAR-T and lasting ≥ 14 days.

  within 28 (+3) days after receiving the infusion.

Study Arms (5)

patients with relapsed/refractory moderately or severely active systemic lupus erythematosus (SLE)

EXPERIMENTAL

Drug：CD19 CAR-T

Drug: Drug：CD19 CAR-T

relapsed/refractory active diffuse cutaneous systemic sclerosis (dcSSc)

EXPERIMENTAL

Drug：CD19 CAR-T

Drug: Drug：CD19 CAR-T

relapsed/refractory antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV)

EXPERIMENTAL

Drug：CD19 CAR-T

Drug: Drug：CD19 CAR-T

relapsed/refractory idiopathic inflammatory myopathy (IIM)

EXPERIMENTAL

Drug：CD19 CAR-T

Drug: Drug：CD19 CAR-T

relapsed/refractory Sjogren 's syndrome (SS)

EXPERIMENTAL

Drug：CD19 CAR-T

Drug: Drug：CD19 CAR-T

Interventions

Drug：CD19 CAR-T DRUG

A total of 3 dose groups were set, with dose group 1 as the starting dose, which was performed according to the traditional 3 + 3 design rule as a single intravenous infusion.

patients with relapsed/refractory moderately or severely active systemic lupus erythematosus (SLE); relapsed/refractory Sjogren 's syndrome (SS); relapsed/refractory active diffuse cutaneous systemic sclerosis (dcSSc); relapsed/refractory antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV); relapsed/refractory idiopathic inflammatory myopathy (IIM)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 、aged 18 to 65 years (including 18 and 65 years), male or female;
• 、Special criteria for different indications:
• Subjects with relapsed/refractory moderate to severe SLE must meet the following criteria:
• \) diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE;
• \) positive antinuclear antibody (ANA) (titer ≥ 1:80), and/or positive anti-dsDNA -antibody, and/or positive anti-Sm antibody at screening;
• \) 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;
• \) 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);
• Subjects with relapsed/refractory dcSSc were required to meet the following criteria:
• \) diagnosis of SSc according to the 2013 EULAR/ACR classification criteria for systemic sclerosis (SSc);
• \) diffuse cutaneous manifestations according to the 1988 LeRoy et al criteria, ie, extensive skin fibrosis with proximal elbow and/or knee skin involvement;
• \) 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;
• \) 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;
• \) 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.
• Subjects with/refractory AAV must meet the following criteria:
• \) a clinical diagnosis of granulomatous vasculitis (GPA) and microscopic polyangiitis (MPA) as defined by the 2012 Chapel Hill Consensus Conference (CHCC);

You may not qualify if:

• \. patients with previous or concurrent other active malignancies, including tumor-associated polymyositis/dermatomyositis. Cured or at least 2 years without recurrence of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or radical treatment of local prostate cancer, ductal carcinoma in situ after radical resection;
• \. combined with severe lung disease in the past 3 months, such as moderate to severe pulmonary hypertension (mean pulmonary arterial pressure \> 60 mmHg by echocardiography), oxygen therapy with oxygen mask or non-invasive or invasive ventilator-assisted respiration during screening;
• \. IgA, IgG, IgM below the lower limit of normal (LLN) at screening;
• \. patients who have used any of the following drugs or treatments within the specified time:
• \) B cell depletion therapy within 1 month before screening and no treatment failure as assessed by clinicians, including targeted CD20, CD22, CD52, CD38, BCMA monoclonal antibody or bispecific antibody;
• \) high-dose human intravenous immunoglobulin within 1 month before screening; -3) Use of therapeutic doses of glucocorticoids (prednisone ≥ 20 mg/day or equivalent doses of other corticosteroids) within 24 hours before Qinglin pretreatment;
• \) Has received corticosteroid pulse therapy (defined as doses ≥ 500 mg/day prednisone or equivalent doses of other corticosteroids) within 2 weeks;
• \) has received taitacept within 2 weeks prior to Screening or belimumab within 3 weeks;
• \. Patients with a history of severe central nervous system disease or related symptoms (excluding trigeminal nerve disease alone) in the past 6 months, including but not limited to: lupus encephalopathy, cerebrovascular disease, encephalitis, brain injury, aneurysm, cerebellar disease, organic brain syndrome, Parkinson's disease and other central nervous system diseases, as well as epilepsy, convulsions, aphasia, dementia and other symptoms;
• \. Lupus crisis occurred within 3 months before screening, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe granulocytopenia, severe myocardial injury, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, severe vasculitis, etc.;
• \. Patients with severe kidney disease: severe lupus nephritis within 8 weeks before screening \[defined as urine protein \> 4g/24 hours or serum creatinine \> 1.5 × ULN or creatinine clearance (Cockcroft Gault formula) \< 30 mL/min;\], or active nephritis requiring the use of drugs prohibited by the regimen, or requiring prednisone greater than 500 mg/d or other effective treatment for ≥ 14 days;
• \. Patients who are severely allergic to the Qinglin pretreatment drugs used in this study and any component of autologous CD19 CAR-T;
• \. hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA positive; hepatitis C virus (HCV) antibody positive and HCV RNA positive; treponema pallidum antibody positive; HIV antibody positive;
• \. the presence of uncontrolled fungi, bacteria, viruses or other infections that are not suitable for participation in the study as assessed by the investigator;
• \. history of major organ transplantation (such as heart and lung);

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Chinese Academy of Medical Sciences Hospital of Hematology (Chinese Academy of Medical Sciences Institute of Hematology), Tianjin, 300020

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Autoimmune Diseases

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• wang ying

  wangying1@ihcams.ac.cn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

wang ying

CONTACT

022-23909095; wangying1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 8, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)