Systemic Lupus ErythematosusPhase 1NCT06316076
Safety and Efficacy Study of CD19-CAR-DNT Cells in Autoimmune Diseases
A Phase 1 study testing CD19-CAR-DNT cells in people with Systemic Lupus Erythematosus and Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by RenJi Hospital at 1 site in China.
Trial summary
To evaluate the safety and efficacy of CD19-CAR-DNT cells in subjects with relapsed/refractory autoimmune diseases Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Systemic Lupus Erythematosus, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Idiopathic Inflammatory Myopathies
- What is being tested?
- CD19-CAR-DNT cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 30 Oct 2023to Jun 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment;
- Aged 18 to 75 years (including cut-offs), regardless of gender;
- Appropriate organ function, and accordance with the following criteria within 7 days prior to lymphodepleting chemotherapy:
- Coagulation function: a) Fibrinogen ≥1.0 g/L; b) Activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN); c) Prothrombin time (PT) ≤1.5 times ULN;
- Liver function: a) Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN); b) Glutamic aminotransferase (ALT) ≤ 3 times ULN; c) Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome. Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 1.5 times ULN may be included;
- Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine clearance ≥ 60 mL/min (see Appendix 2 for Cockcroft-Gault formula);
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- Complete blood count: a) Hemoglobin ≥ 80 g/L or hemoglobin maintained at that level following transfusion; b) absolute neutrophil count (ANC) ≥ 1.0×10^9/L; c) A platelet count ≥ 30 x 10^9/L or a platelet count maintained at that level following a platelet transfusion;
- Cardiopulmonary function: left ventricular ejection fraction (LVEF) ≥45%;
- Female patients with of childbearing potential should have a negative pregnancy test during the screening period. Any male and female patients of childbearing potential must agree to use an effective contraception method for at least six months from the time that they sign the informed consent form until the end of the cell infusion. Female patients without childbearing potential (meeting at least 1 of the following criteria) is described below:
- Have undergone a hysterectomy or bilateral oophorectomy;
- Medically recognized as ovarian failure;
- Medically recognized as post-menopausal (at least 12 consecutive months of menopause without pathological or physiological cause);
- Meets the criteria of relapsed/refractory autoimmune diseases in 2022 EULAR/ACR.
Who cannot join
- Individuals with a history of severe drug allergies or allergic constitution;
- Active infectious diseases: such as tuberculosis, central nervous system infection, hepatitis, enteritis, etc.;
- The following serious diseases: malignant tumor, end-stage renal failure, alveolar hemorrhage requiring mechanical ventilation, acute mononeuritis multiplex, or CNS involvement;
- Renal disease: creatinine clearance rate < 60mL/min and serum creatinine > 1.5 times ULN within 1 week before lymphodepleting chemotherapy; Patients required hemodialysis or high-dose glucocorticoid therapy (e.g., prednisone (or equivalent) ≥100mg per day) within 6 months before screening;
- Cardiovascular disease: unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction, New York Heart Association class III or IV cardiac dysfunction, or refractory hypertension within 6 months before screening (refractory hypertension was defined as: on the basis of lifestyle modification, patients were treated with adequate and reasonably tolerable doses of ≥3 antihypertensive drugs (including diuretics) for > 1 month or with ≥4 antihypertensive drugs for effective blood pressure control) and a history of severe arrhythmia requiring drug treatment;
- Other uncontrollable diseases: clinically unstable or not effectively controlled acute/chronic diseases unrelated to AID (such as acute pneumonia, diabetic ketoacidosis, acute pancreatitis, etc.) that may confound study results or affect investigators' assessment of efficacy/safety;
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- Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titration assay not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA, positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test;
- The presence of active or uncontrollable infections requiring systemic treatment (except simple urinary tract infections or upper respiratory tract infections) and currently receiving suppressive therapy for any chronic infection (e.g., tuberculosis, Pneumocystis carinii, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria);
- Vaccination with live or attenuated live vaccine within 1 month before screening;
- Persons who have previously received an organ transplant or are preparing to receive an organ transplant;
- Patients have received CAR-T therapy or other gene-modified cell therapy prior to enrolment;
- Received rituximab treatment within 6 months prior to screening; Received belimumab and telitacicept within 30 days prior to initial administration of the investigational drug; JAK inhibitor discontinuation time is less than 5 half-lives;
- Patients with a life expectancy of less than 3 months;
- Patients have been involved in other clinical studies within 3 months prior to screening;
- Patients, in the judgement of the investigator and/or clinical criteria, are contraindicated to any study procedure or have other medical conditions that may place them at unacceptable risk.
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Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University
Shanghai
Qiong Fu, MD, PhD, 86-13585603288, fuqiong@renji.com
Shuang Ye, MD, PhD, 86-15801706421, Yeshuang@renji.com
About this study
Official title: A Clinical Study for the Safety and Efficacy of CD19-CAR-DNT Cells (RJMty19) in the Treatment of Relapsed or Refractory Autoimmune Diseases
To evaluate the safety and efficacy of CD19-CAR-DNT cells in subjects with relapsed/refractory autoimmune diseases
Read the detailed description
This is an open, single-arm, single-dose, dose-escalation and dose-expansion clinical trial designed to evaluate the maximum tolerated dose of CD19-CAR-DNT cells, the safety, the preliminary efficacy and the pharmacokinetic profile of CD19-CAR-DNT cells in patients after infusion. 8-24 patients are planned to be enrolled in the dose-escalation trial and 12-24 patients in the dose-expansion trial. The primary endpoints are DLT, MTD, and the incidence of abnormalities in AE/SAE/AESI/laboratory test.
- Conditions
- Systemic Lupus Erythematosus, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Idiopathic Inflammatory Myopathies, Systemic Sclerosis
- Being tested
- CD19-CAR-DNT cells
- Medical subject headings
- Lupus Erythematosus, Systemic, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Myositis, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19-CAR-DNT cellsBiological
Also called Cyclophosphamide, Fludarabine
Lentiviral vector-transduced DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| CD19-CAR-DNT cells | Experimental | 8-24 patients are planned to be enrolled in the dose-escalation trial and 12-24 patients in the dose-expansion trial. Receives: Biological: CD19-CAR-DNT cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory autoimmune disease.
Measured: Up to 28 days
MTD
MTD was the highest dose for DLT in ≤1/6 subjects.
Measured: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Measured: Up to 28 days
Secondary outcomes (6)
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of CD19-CAR-DNT cells amplified in the peripheral blood (Cmax, detected by qPCR).
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by qPCR)
Measured: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the peak plasma time (Tmax). Tmax is defined as the time to reach the highest concentration (Tmax, detected by qPCR).
Measured: Up to 2 years
Pharmacokinetics (PK) indicator (T1/2)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of CD19-CAR-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by qPCR).
Measured: Up to 90 days
Disease response rate at 6 months
Proportion of subjects with complete or partial remission.
Measured: Up to 6 months
Duration of Response
The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start30 Oct 2023
- Primary completionJun 2024 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe 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
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Ruishun Biotech Co., Ltd
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06316076
- Sponsor's protocol ID
- RJMty19-AID001
- Status last verified
- Mar 2024
- First submitted
- 12 Mar 2024
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study for the Safety and Efficacy of CD19-CAR-DNT Cells (RJMty19) in the Treatment of Relapsed or Refractory Autoimmune Diseases
- ClinicalTrials.gov ID
- NCT06316076
- Acronym / sponsor ID
- RJMty19-AID001
- Conditions
- Systemic Lupus Erythematosus, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Idiopathic Inflammatory Myopathies, Systemic Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- Guangdong Ruishun Biotech Co., Ltd
- Study start
- 30 Oct 2023 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 18 Mar 2024 (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.
To evaluate the safety and efficacy of CD19-CAR-DNT cells in subjects with relapsed/refractory autoimmune diseases
Detailed description
This is an open, single-arm, single-dose, dose-escalation and dose-expansion clinical trial designed to evaluate the maximum tolerated dose of CD19-CAR-DNT cells, the safety, the preliminary efficacy and the pharmacokinetic profile of CD19-CAR-DNT cells in patients after infusion. 8-24 patients are planned to be enrolled in the dose-escalation trial and 12-24 patients in the dose-expansion trial. The primary endpoints are DLT, MTD, and the incidence of abnormalities in AE/SAE/AESI/laboratory test.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19-CAR-DNT cells | Experimental | Biological: CD19-CAR-DNT cells8-24 patients are planned to be enrolled in the dose-escalation trial and 12-24 patients in the dose-expansion trial. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment;
- Aged 18 to 75 years (including cut-offs), regardless of gender;
- Appropriate organ function, and accordance with the following criteria within 7 days prior to lymphodepleting chemotherapy:
- Coagulation function: a) Fibrinogen ≥1.0 g/L; b) Activated partial thromboplastin time ≤1.5 times the upper limit of normal (ULN); c) Prothrombin time (PT) ≤1.5 times ULN;
- Liver function: a) Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN); b) Glutamic aminotransferase (ALT) ≤ 3 times ULN; c) Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome. Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 1.5 times ULN may be included;
Key exclusion criteria (16 listed)
- Individuals with a history of severe drug allergies or allergic constitution;
- Active infectious diseases: such as tuberculosis, central nervous system infection, hepatitis, enteritis, etc.;
- The following serious diseases: malignant tumor, end-stage renal failure, alveolar hemorrhage requiring mechanical ventilation, acute mononeuritis multiplex, or CNS involvement;
- Renal disease: creatinine clearance rate < 60mL/min and serum creatinine > 1.5 times ULN within 1 week before lymphodepleting chemotherapy; Patients required hemodialysis or high-dose glucocorticoid therapy (e.g., prednisone (or equivalent) ≥100mg per day) within 6 months before screening;
- Cardiovascular disease: unstable angina, cerebrovascular accident or transient ischemic attack, myocardial infarction, New York Heart Association class III or IV cardiac dysfunction, or refractory hypertension within 6 months before screening (refractory hypertension was defined as: on the basis of lifestyle modification, patients were treated with adequate and reasonably tolerable doses of ≥3 antihypertensive drugs (including diuretics) for > 1 month or with ≥4 antihypertensive drugs for effective blood pressure control) and a history of severe arrhythmia requiring drug treatment;
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-CAR-DNT cellsAlso: Cyclophosphamide, FludarabineLentiviral vector-transduced DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy. | Biological | CD19-CAR-DNT cells |
Primary outcome
DLT
Time frame: Up to 28 days
To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory autoimmune disease.
MTD
Time frame: Up to 28 days
MTD was the highest dose for DLT in ≤1/6 subjects.
Incidence of abnormalities
Time frame: Up to 28 days
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
6 secondary outcomes
Pharmacokinetics (PK) indicator (Cmax)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
Time frame: Up to 2 years
Pharmacokinetics (PK) indicator (T1/2)
Time frame: Up to 90 days
Disease response rate at 6 months
Time frame: Up to 6 months
Duration of Response
Time frame: Up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Individual participant dataSharing planned: No
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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.
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-CAR-DNT cells in people with Systemic Lupus Erythematosus and Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by RenJi Hospital 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 13 inclusion and 16 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 18 Mar 2024. 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 Qiong Fu, MD, PhD (+086-13585603288, fuqiong@renji.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: Up to 28 days). The study lists 3 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 18 Mar 2024.