Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease

NCT06056921 | Recruiting Phase 1

• 1 other identifier: PBC054
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm study to evaluate the efficacy and safety of CD19 targeted CAR-T cells therapy for patients with Refractory Autoimmune Disease

Conditions

SLE (Systemic Lupus); Sjogren's Syndrome; Systemic Scleroderma; Dermatomyositis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Keywords

CAR-T; CD19

Outcome Measures

Primary Outcomes (7)

• Incidence of Adverse events after CD19 CAR-T cells infusion [Safety and Tolerability]

  Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

  1 month

• Obtain the maximum tolerated dose of CD19 CAR-T cells[Safety and Tolerability]

  Dose-limiting toxicity after cell infusion

  1month

• Efficacy of CAR-T cell preparations in Refractory systemic lupus erythematosus [Effectiveness]

  The efficacy is assessed by SRI-4 response rate at 3M，SRI-4 response rate at 3M means Percentage of patients who met all three of the following conditions at 3M after refusion: 1. The SLEDAI-2K rating dropped by at least 4 points 2. No deterioration in PGA scores on a 3-point scale (deterioration is defined as an increase of ≥0.3 points from baseline score) 3. No new manifestations of organ system involvement (new system involvement is defined as one or more new symptoms of BILAG grade A or two or more symptoms of BILAG B)

  3 months

• Efficacy of CAR-T cell preparations in Refractory Systemic scleroderma [Effectiveness]

  The efficacy is assessed by Change value of The EULAR Sjögren's syndrome disease activity index（ESSDAI）score at 3M

  3 months

• Efficacy of CAR-T cell preparations in Refractory Sjogren's syndrome [Effectiveness]

  The efficacy is assessed by Change value of modified Rondan skin score（mRSS） at 3M； The evaluator palpated 17 areas of the patient's body. The skin thickness of each area was calculated on a scale of 0 to 3 points. The total score was 51 points, 0 was normal skin with fine lines and no skin thickening. 1 is divided into mild skin thickening, the inspector can easily use two fingers to pinch the skin to form wrinkles, skin fine lines can also exist; 2: moderate skin thickening, more difficult to pinch the skin to form wrinkles, skin fine lines disappear; 3 is classified as severe skin thickening, unable to pinch the skin to form wrinkles.

  3 months

• Efficacy of CAR-T cell preparations in Refractory dermatomyositis [Effectiveness]

  The efficacy is assessed by CSM Total Improvement Score (TIS) 20/40/60 improvement rate at 3M；3M CSM Total Improvement Score (TIS) 20/40/60 Improvement rate: defined as the proportion of patients with a TIS score of 20-40,40-60, and ≥60 at 3M posttransfusion

  3 months

• Efficacy of CAR-T cell preparations in Refractory The antineutrophil cytoplasmic antibody-associated vasculitides [Effectiveness]

  The efficacy is assessed by response rate at 3M； Defined as the percentage of patients whose BVAS score decreased to 0 at 3M after reinfusion in the absence of glucocorticoids and other therapeutic agents

  3 months

Secondary Outcomes (6)

• AUCS of CD19 CAR-T cells [Cell dynamics]

  3 months

• CMAX of CD19 CAR-T cells [Cell dynamics]

  3 months

• TMAX of CD19 CAR-T cells[Cell dynamics]

  3 months

• Pharmacodynamics of CD19 CAR-T cells[Cell dynamics]

  3 months

• Immunogenicity after infusion of CD19 CAR-T

  2 years

Other Outcomes (5)

• Refractory systemic lupus erythematosus -specific secondary study endpoint [Effectiveness]

  2 years

• Refractory Systemic scleroderma-specific secondary study endpoint [Effectiveness]

  2 years

• Refractory Sjogren's syndrome-specific secondary study endpoint [Effectiveness]

  2 years

Study Arms (1)

CD19-targeted CAR-T

EXPERIMENTAL

CD19 targeted CAR-T cells treat

Biological: CD19 targeted CAR-T cells

Interventions

CD19 targeted CAR-T cells BIOLOGICAL

A single infusion of CD19 CAR-T cells will be administered intravenously

CD19-targeted CAR-T

Eligibility Criteria

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

You may qualify if:

• ≥18 years old, male or female;
• diagnosed with one of the following diseases:
• Systemic Lupus Erythematosus (SLE), EULAR/ACR 2019 standard;
• Sjogren's Syndrome (SS), 2016 ACR/EULAR standard;
• Systemic Scleroderma (SSc), 2013 ACR/EULAR Standards;
• Dermatomyositis (DM), 2017 EULAR/ACR classification standard + one positive myositis specific antibody (Jo-1, Zo, EJ, PL-7, KS, OJ, PL-12, YRS, Anti-NXP-2, Anti-TIF1g, Anti-Mi-2, Anti-SAE, Anti-MDA-5, Anti-SRP, Anti-HMGCR);
• Anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-AAV), including granulomatosis with polyangiitis (GPA), or microscopic vasculitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA), 2022 ACR/EULAR standard.
• Disease activity meets the following requirements:
• SLEDAI score ≥8 for SLE patients;
• For SS patients, ESSDAI≥14 points;
• For patients with SSc, mRSS score in the range of 10-35 (including the boundary value) with interstitial pneumonia (ILD);
• Patients with DM who have been diagnosed for at least 1 year and meet the following conditions:
• \. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;
• , muscle biopsy pathology or muscle nuclear magnetic evidence of active inflammation;
• \. Bilateral manual muscle strength test (MMT-8) is less than 125/150, and at least 2 additional Core set measures (CSM) meet the following criteria: Patient score, 10 cm visual analogue scale (VAS) no less than 2.0 cm; b. Physician score, no less than 2.0 cm on the 10 cm VAS scale; c. Health Assessment Questionnaire (HAQ) disability index (Appendix 10) of not less than 0.25; d. Elevation of at least one muscular enzyme (including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), with a minimum level of 1.3× the upper limit of normal; e. Disease activity score of extramuscular organs, no less than 1.0 cm on the 10 cm VAS scale (this VAS is the physician's comprehensive assessment of myositis disease Activity Assessment Tool (MDAAT) based on the general condition, skin, bone, gastrointestinal, lung, and heart scale activity score);

You may not qualify if:

• Had previously received CAR T cell therapy;
• patients with serious heart, liver, lung, blood system, endocrine system diseases, and the risk of participating in the trial is higher than the benefit judged by the researcher;
• There is an active or uncontrollable infection that requires systemic treatment within 1 week prior to screening;
• have previously received hematopoietic stem cell transplantation or solid organ transplantation (except corneal and hair transplantation), or have grade 2 or higher acute graft-versus-host disease (GVHD) within 2 weeks prior to screening;
• Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
• Had received live vaccine within 4 weeks before screening;
• pregnancy test positive;
• Patients with malignant diseases such as malignant tumors before screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery;
• Patients who had participated in other clinical trials within 3 months prior to screening;
• Situations in which other investigators consider it inappropriate to participate in the study.

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Sjogren's Syndrome; Scleroderma, Systemic; Dermatomyositis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Skin Diseases; Polymyositis; Myositis; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular

Study Officials

• Liyun Zhang, M.D

  Shanxi Bethune Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liyun Zhang, M.D

CONTACT

13834547708; 1315710223@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: September 28, 2023
• Study Start: August 31, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): August 31, 2026
• Last Updated: September 28, 2023

Record last verified: 2023-08

Locations

CN (1)