SLE (Systemic Lupus)Phase 1NCT06056921
Safety and Efficacy of CD19 Targeted CAR-T Therapy for Refractory Autoimmune Disease
A Phase 1 study testing CD19 targeted CAR-T cells in people with SLE (Systemic Lupus) and Sjogren's Syndrome, run by Chongqing Precision Biotech Co., Ltd at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SLE (Systemic Lupus), Sjogren's Syndrome, Systemic Scleroderma
- What is being tested?
- CD19 targeted CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 31 Aug 2023to 31 Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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);
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- 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:
- 1. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;
- 2, muscle biopsy pathology or muscle nuclear magnetic evidence of active inflammation;
- 3. 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);
- For ANCA-AAV patients, the BVAS score was ≥15.
- ECOG 0~1 score;
- The functions of important organs are basically normal:
- Hematology: hemoglobin ≥60g/L, platelet count ≥30×109/L;
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram;
- Renal function: eGFR≥30ML/min/1.73m2;
- Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0 ULN;
- Lung function: DLCO≥40% predicted value; FVC≥50% expected value;
- Have criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
- The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
- The patient or his/her guardian agrees to participate in the clinical trial and signs the informed consent, indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanxi Bethune Hospital
Taiyuan, Shanxi
Liyun Zhang, MD, 13834547708, 1315710223@qq.com
About this study
Official title: Clinical Study of CD19 Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Refractory Autoimmune Diseases
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
Read the detailed description
the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. Otherwise, some studies have shown that the use of CD19-targeted CAR-T therapy in refractory SLE can improve the autoimmune symptoms of patients, and at the same time, immunosuppressants and hormones can be stopped to maintain long-term autoimmune indicators normal.To verify the safety and efficacy, the investigators launch such a clinical trial using CD19 targeted CAR-T cells for patients with Refractory Autoimmune Disease.
- Conditions
- SLE (Systemic Lupus), Sjogren's Syndrome, Systemic Scleroderma, Dermatomyositis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- Being tested
- CD19 targeted CAR-T cells
- Keywords
- CAR-T, CD19
- Medical subject headings
- Lupus Erythematosus, Systemic, Sjogren's Syndrome, Scleroderma, Systemic, Dermatomyositis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 targeted CAR-T cellsBiological
A single infusion of CD19 CAR-T cells will be administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| CD19-targeted CAR-T | Experimental | CD19 targeted CAR-T cells treat Receives: Biological: CD19 targeted CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 1 month
Obtain the maximum tolerated dose of CD19 CAR-T cells[Safety and Tolerability]
Dose-limiting toxicity after cell infusion
Measured: 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:
- The SLEDAI-2K rating dropped by at least 4 points
- No deterioration in PGA scores on a 3-point scale (deterioration is defined as an increase of ≥0.3 points from baseline score)
- 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)
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 3 months
Secondary outcomes (6)
AUCS of CD19 CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
Measured: 3 months
CMAX of CD19 CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CD70 CAR-T cells expanded in peripheral blood
Measured: 3 months
TMAX of CD19 CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Measured: 3 months
Pharmacodynamics of CD19 CAR-T cells[Cell dynamics]
Pharmacodynamics is defined as the degree of B cell clearance at each time point
Measured: 3 months
Immunogenicity after infusion of CD19 CAR-T
Positive rate of anti-CAR antibody in peripheral blood
Measured: 2 years
Immunological reconstitution of CAR-T after infusion of CD19 CAR-T
The change curve of B cells in peripheral blood after transfusion;
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2023
- Study start31 Aug 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SLE (Systemic Lupus)Studies of the same condition, open and under way.
- More trials run by Chongqing Precision Biotech Co., LtdThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chongqing Precision Biotech Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Liyun Zhang, M.D, Principal investigator, Shanxi Bethune Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06056921
- Sponsor's protocol ID
- PBC054
- Status last verified
- Aug 2023
- First submitted
- 18 Aug 2023
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of CD19 Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Refractory Autoimmune Diseases
- ClinicalTrials.gov ID
- NCT06056921
- Acronym / sponsor ID
- PBC054
- Conditions
- SLE (Systemic Lupus), Sjogren's Syndrome, Systemic Scleroderma, Dermatomyositis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- Keywords
- CAR-T, CD19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Chongqing Precision Biotech Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 28 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. Otherwise, some studies have shown that the use of CD19-targeted CAR-T therapy in refractory SLE can improve the autoimmune symptoms of patients, and at the same time, immunosuppressants and hormones can be stopped to maintain long-term autoimmune indicators normal.To verify the safety and efficacy, the investigators launch such a clinical trial using CD19 targeted CAR-T cells for patients with Refractory Autoimmune Disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19-targeted CAR-T | Experimental | Biological: CD19 targeted CAR-T cellsCD19 targeted CAR-T cells treat |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- ≥18 years old, male or female;
- diagnosed with one of the following diseases:
- Disease activity meets the following requirements:
- 1. Skin rash VAS score (based on MDAAT) ≥3cm with at least 3 abnormalities in CSM;
- 2, muscle biopsy pathology or muscle nuclear magnetic evidence of active inflammation;
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD19 targeted CAR-T cellsA single infusion of CD19 CAR-T cells will be administered intravenously | Biological | CD19-targeted CAR-T |
Primary outcome
Incidence of Adverse events after CD19 CAR-T cells infusion [Safety and Tolerability]
Time frame: 1 month
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)
Obtain the maximum tolerated dose of CD19 CAR-T cells[Safety and Tolerability]
Time frame: 1month
Dose-limiting toxicity after cell infusion
Efficacy of CAR-T cell preparations in Refractory systemic lupus erythematosus [Effectiveness]
Time frame: 3 months
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)
Efficacy of CAR-T cell preparations in Refractory Systemic scleroderma [Effectiveness]
Time frame: 3 months
The efficacy is assessed by Change value of The EULAR Sjögren's syndrome disease activity index（ESSDAI）score at 3M
Efficacy of CAR-T cell preparations in Refractory Sjogren's syndrome [Effectiveness]
Time frame: 3 months
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.
Efficacy of CAR-T cell preparations in Refractory dermatomyositis [Effectiveness]
Time frame: 3 months
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
Efficacy of CAR-T cell preparations in Refractory The antineutrophil cytoplasmic antibody-associated vasculitides [Effectiveness]
Time frame: 3 months
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
6 secondary outcomes
AUCS of CD19 CAR-T cells [Cell dynamics]
Time frame: 3 months
CMAX of CD19 CAR-T cells [Cell dynamics]
Time frame: 3 months
TMAX of CD19 CAR-T cells[Cell dynamics]
Time frame: 3 months
Pharmacodynamics of CD19 CAR-T cells[Cell dynamics]
Time frame: 3 months
Immunogenicity after infusion of CD19 CAR-T
Time frame: 2 years
Immunological reconstitution of CAR-T after infusion of CD19 CAR-T
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Liyun Zhang, M.D principal investigator
Shanxi Bethune Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19 targeted CAR-T cells in people with SLE (Systemic Lupus) and Sjogren's Syndrome, run by Chongqing Precision Biotech Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Liyun Zhang, M.D (13834547708, 1315710223@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse events after CD19 CAR-T cells infusion [Safety and Tolerability] (time frame: 1 month). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.