BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases

NCT06794008 | Recruiting Phase 2 DMC

• 1 other identifier: ICG318-AAV-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the efficacy and safety of BCMA/CD19 chimeric antigen receptor (CAR)-modified T cells in the treatment of autoimmune diseases.

Conditions

Systemic Lupus Erythematosus; Inflammatory Myopathy; Systemic Sclerosis (SSc); ANCA-associated Vasculitis; IgG4-Related Diseases; Antiphospholipid Syndrome; Acquired Thrombotic Thrombocytopenic Purpura; Behcet Disease; Sjogren Syndrome

Keywords

CAR-T; CD19; BCMA

Outcome Measures

Primary Outcomes (9)

• Systemic Lupus Erythematosus primary outcome

  Percentage of SLE participants who had a response on the SLE Responder Index (SRI-4) at 24 weeks. The Systemic Lupus Erythematosus Responder Index-4 (SRI-4) was used to assess the treatment efficacy in systemic lupus erythematosus (SLE).The scale ranges from 0 to 105, with higher scores indicating worse disease activity. A response is defined as a ≥4-point improvement from baseline at 24 weeks

  From enrollment to the end of treatment at 24 weeks

• Sjogren syndrome primary outcome

  Proportion of participants with a Sjögren's Tool for Assessing Response (STAR) score of greater than or equal to five at 24 weeks. The STAR is a composite score used to evaluate the clinical response in patients with Sjögren's syndrome. The STAR score ranges from 0 to 9, with higher scores indicating better clinical response. A score of ≥5 at 24 weeks indicates a positive response to treatment.

  From enrollment to the end of treatment at 24 weeks

• Inflammatory Myopathy primary outcome

  TIS ranges from 0 to 100, with a higher score denoting greater improvement. In adults, TIS can be stratified into the following improvement categories for each patient at each timepoint (minimal improvement \[TIS ≥20\]; moderate improvement \[TIS ≥40\]; major improvement \[TIS ≥60\]). Thus, in the above example the patient would be classified as having moderate improvement \[TIS ≥40\].

  From enrollment to the end of treatment at 24 weeks

• Systemic Sclerosis primary outcome

  Change in the Modified Rodnan Skin Score (mRSS) at 24 weeks compared to baseline. The mRSS is a clinical tool used to assess the severity of skin thickening in patients with systemic sclerosis (scleroderma). The mRSS ranges from 0 to 51, with higher scores indicating more severe skin thickening. A decrease in the mRSS score indicates an improvement in skin involvement

  From enrollment to the end of treatment at 24 weeks

• Behçet's Disease primary outcome

  Proportion of participants with complete remission of oral ulcers at 24 weeks. Oral ulcer resolution is defined as the complete disappearance of all oral ulcers, as observed during clinical examination. A participant is considered to have achieved complete remission if no oral ulcers are present at the 24-week visit

  From enrollment to the end of treatment at 24 weeks

• ANCA associated Vasculitis primary outcome

  Proportion of participants achieving Birmingham Vasculitis Activity Score (BVAS) of 0 at 24 weeks. BVAS is a composite score used to assess disease activity in vasculitis, ranging from 0 to 63 or higher. Higher scores indicate more severe disease activity. A decrease in BVAS at 24 weeks indicates an improvement in disease activity.

  From enrollment to the end of treatment at 52 weeks

• Antiphospholipid Syndrome primary outcome

  Number and timing of thrombotic events occurring within 52 weeks.

  From enrollment to the end of treatment at 52 weeks

• Acquired Thrombotic Thrombocytopenic Purpura primary outcome

  Time to normalization of platelet count.

  From enrollment to the end of treatment at 52 weeks

• IgG4-related Disease primary outcome

  Proportion of participants with a decrease of greater than or equal to two points in the IgG4-related Disease Responder Index (IgG4RD RI) at 24 weeks compared to baseline. The IgG4RD RI is a composite score used to assess the response to treatment in IgG4-related disease. The score ranges from 0 to 63, with higher scores indicating worse disease activity. A decrease of ≥2 points at 24 weeks indicates a meaningful improvement in disease activity compared to baseline

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (9)

• Systemic Lupus Erythematosus primary secondary Outcome

  From enrollment to the end of treatment at 24 weeks

• Sjogren syndrome secondary outcome

  From enrollment to the end of treatment at 24 weeks

• Inflammatory Myopathy secondary outcome

  From enrollment to the end of treatment at 24 weeks

• Systemic Sclerosis secondary outcome

  From enrollment to the end of treatment at 24 weeks

• Behçet's Disease secondary outcome

  From enrollment to the end of treatment at 24 weeks

Study Arms (1)

CAR-T treatment in patients with multiple refractory autoimmune diseases

EXPERIMENTAL

Patients received the BCMA-CD19-targeted CAR-T cells with a dosage of 3×10\^6/kg CAR-T cells per kilogram.

Drug: BCMA-CD19 CAR-T therapy

Interventions

BCMA-CD19 CAR-T therapy DRUG

Patients received the BCMA-CD19-targeted CAR-T cells with a dosage of 3×10\^6/kg CAR-T cells per kilogram.

CAR-T treatment in patients with multiple refractory autoimmune diseases

Eligibility Criteria

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

You may qualify if:

• Age, 18-65 years old (inclusive), weight \>=45kg, male and female;
• The diagnosis of each disease meets the following criteria:
• Systemic lupus erythematosus: 1997 ACR classification criteria or 2012 SLICC classification criteria Sjögren's syndrome: 2002 International Classification of Sjögren's Syndrome Inflammatory myopathies: 1977 Bohan Recommendation Systemic sclerosis: 1980 ACR classification criteria or 2013 ACR-EULAR classification criteria Behcet's disease: 1989 International Classification Criteria for Behcet's disease ANCA-associated vasculitis: 1990 ACR classification criteria IgG4-related disease: 2011 IgG4-RD composite diagnostic criteria Antiphospholipid syndrome: 2006 revision of the Sapporo APS classification criteria Acquired thrombotic thrombocytopenic purpura: consistent with a clinical diagnosis of TTP, including microscopic evidence of thrombocytopenia and red blood cell fragmentation (e.g., red blood cell fragmentation) 3. Multiple treatment regimens are ineffective or ineffective (including but not limited to high-dose glucocorticoids, adequate immunosuppressants and biologics) 4. Use of glucocorticoids (\<=1mg/kg/d prednisone or equivalent doses of other hormones), DMARDs (such as methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, leflunomide, cyclosporine, etc.) must be on stable treatment for 4 weeks before receiving the first study drug, and no increase in hormone dose and other immunosuppressants throughout the study.
• \. Subjects voluntarily participate in this study and voluntarily sign the informed consent form; 6. Subjects who have the possibility of having children or whose partners have the possibility of having children must agree to use effective contraception throughout the study period (but cannot use oral estrogen, use estrogen vaginal ring, etc.) 7. Additional enrollment criteria for different diseases (related to the degree of disease activity):
• Patients with Behcet's disease must be active patients who meet the following conditions, and the active phase is defined as the emergence of new symptoms or the deterioration of existing symptoms, and one of the following conditions must be met:
• A. Organ involvement: involvement of any major organ (e.g., ocular lesions, vascular lesions, central nervous system, gastrointestinal system); B. 100% increase in the number of oral or genital ulcers \>=compared to the onset of oral/genital ulcers compared to the first day; or an increase in the number of oral or genital ulcers by 3; C. Canker disease is at least 12 months; D. History of several oral ulcers per month E. Arthritis: \>=50% increase in the number of swollen joints, or 3 more swollen joints; F. Skin lesions (non-oral/genital ulcers): \>= physician overall lesion score increased by \>=50% or by two points in the total score.
• Patients with active inflammatory myopathy need to meet the following additional conditions:
• Active myositis as defined by the Baseline Freehand Muscle Strength Test (MMT-8) of no more than 125/150 and at least 2 additional CSMs that meet the criteria specified below:
• a) Visual Analogue Scale\[VAS\] of patient global activity ≥2 cm, b) physician's global disease activity ≥2 cm, c) Health Assessment Questionnaire (HAQ) Disability Index ≥ 0.25 d) Elevation of at least one muscle enzyme \[including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)\] with a minimum level of 1.3 x upper limit of normal e) Global Extramuscular Disease Activity Score, with a minimum of 1.0 cm on a 10 cm VAS scale \[This measure is a physician's comprehensive assessment based on the assessment of physique, skin, bone, gastrointestinal, lung, and cardiac activity scale activity scores using the Myositis Disease Activity Assessment Tool (MDAAT).
• ANCA-associated vasculitis:
• A. Comply with GPA/MPA/EGPA classification standards; B. Patients with severe vasculitis activity (meeting at least one of the following conditions);
• a) Renal involvement is characterized by one of the following: i. Evidence of glomerulonephritis in any of the following situations: Renal biopsy shows focal necrotizing glomerulonephritis. Active urinary sediment characterized by glomerular hematuria and proteinuria ii. Patients with prior normal or no prior renal disease document, estimated glomerular filtration rate (eGFR) \<50 ml/min/1.73 m2, and prior chronic kidney disease (eGFR \<60 ml/min/1.73 m2) showed a reduction in eGFR of at least 25% compared with the previous one.
• b) Pulmonary hemorrhage due to active vasculitis satisfies all three of the following: i. Chest X-ray or CT scan showing diffuse pulmonary infiltrates ii. Pulmonary infiltrates that cannot be explained by other causes (e.g., volume overload or pulmonary infection) iii. At least one of the following: Evidence of alveolar hemorrhage on bronchoscopy or bloody bronchoalveolar lavage Hemoptysis was observed Unexplained anemia (\<10 g/dL) or decreased hemoglobin (\>1 g/dL) and less than 10g/dL Increased carbon dioxide dispersion
• Additional Enrollment Criteria for Systemic Sclerosis:
• Subjects are at high risk of fatal outcomes based on the following prognostic factors: Subjects must have the following "a" , and at least one of "b" or "c".

You may not qualify if:

• Use of rituximab or other monoclonal antibodies within 1.6 months.
• Received high-dose glucocorticoids (\>1 mg/kg/d) within 1 month.
• Serious complications: including heart failure (\>= NYHA Class III), renal insufficiency (creatinine clearance \<=30 ml/min), hepatic insufficiency (serum ALT or AST greater than three times the upper limit of normal, or total bilirubin greater than the upper limit of normal)
• Other severe, progressive, or uncontrollable hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral diseases (including demyelinating diseases such as multiple sclerosis).
• Known allergies, hyperreactivity, or intolerance to IL-2 or its excipients.
• Have a serious infection (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus, tuberculosis infection), or hospitalization for infection, or use of intravenous antibiotics for treatment of infection 2 months prior to the first dose of treatment.
• Chest imaging showing malignancy or current activity within 3 months prior to the first use of study drug Abnormalities in sexually transmitted infections (including tuberculosis).
• Infection with HIV (HIV antibody-positive serology) or hepatitis C (Hep C antibody-positive serology).
• If seropositive, it is advisable to consult a physician with expertise in the treatment of HIV or hepatitis C virus infection.
• \. Any known malignancy or history of malignancy within the past 5 years (with the exception of non-melanoma skin cancer, non-melanoma skin cancer with no signs of recurrence or surgically cured cervical tumor within 3 months prior to the use of the first investigational agent).
• \. Have an uncontrolled mental or emotional disorder, including a history of drug and alcohol abuse within the past 3 years, which may preclude the successful completion of the study.
• \. Received or anticipated receipt of any live viral or bacterial vaccine injection within 3 months prior to the first injection of study dose, during the study, or within 4 months after the last injection of study dose. Bacillus Calmette-Guérin vaccination within 12 months of screening.
• \. Pregnant, lactating women (WCBP) who are unwilling to use medically approved contraception during treatment and for 12 months after the end of treatment.
• \. Males whose partner is of childbearing potential but who are unwilling to use appropriate medically approved contraception during treatment and for 12 months after the end of treatment.
• \) Severe muscle impairment is defined as a baseline global muscle impairment score of MDI (Myositis Injury Index) \>=5cm on 10 cm VAS.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Department of Rheumatology and Immunology, Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Myositis; Scleroderma, Systemic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Immunoglobulin G4-Related Disease; Antiphospholipid Syndrome; Purpura, Thrombotic Thrombocytopenic; Behcet Syndrome; Sjogren's Syndrome

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Skin Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Thrombophilia; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases

Study Officials

• Zhanguo Li

  Peking University Institute of Rheuamotology and Immunology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing He

CONTACT

010-88326666; 569975536@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: January 27, 2025
• Study Start: December 26, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 2, 2025

Record last verified: 2024-12

Locations

CN (1)