Systemic Lupus Erythematosus (SLE)
Conditions
Brief summary
This study is a single arm, open, exploratory dose escalation clinical study to evaluate the safety, efficacy, and cellular metabolic dynamics of ct1195e cells in patients with SLE.
Detailed description
The study was divided into dose increasing stage and dose expanding stage.dose escalation phaseThree dose levels are tentatively determined for dose escalation: 3.0 × 108, 4.5 × 108 and 6.0 × 108 car-cd19/CD20+T cells. It is estimated that the target toxicity probability of the maximum tolerated dose is 30%, and about 12 participants are planned to be enrolled, and the number of enrolled patients in each dose group is subject to the actual situation. During the test, the researchers and partners will jointly negotiate whether to increase or decrease the dose, whether to increase to the set maximum dose group or produce the maximum available cell volume, and whether to increase the exploration of new dose level within the explored dose range (allowed to be conducted when the dose is increased or decreased) according to the participants' cell metabolism characteristics, safety, tolerance and preliminary effectiveness data, so as to determine the possible recommended therapeutic dose (RD).The DLT observation period is 28 days after the first infusion. If the treatment needs to be withdrawn before 28 days after the infusion due to disease progression or other reasons, no obvious car-t cell expansion is detected or car-t treatment is invalid, and the DLT related AE events determined by the researcher may not be related to the product, the DLT observation period can be completed before. During each dose increase, if there is a safety risk that needs to be discussed, the researchers and partners can make a dose increase/stability/decrease decision according to the safety and tolerance of participants and the metabolic kinetics of ct1192 cells. In the same dose group, the first participant had no significant safety risk 14 days after the completion of cell infusion, and subsequent participants could only carry out cell infusion.dose expansion phaseOne or more dose groups may be selected for dose expansion according to the results of the dose increasing stage to further explore the efficacy and safety in SLE patients. Each dose group and each queue plan to include up to 9 cases, and the specific number of patients in the group is subject to the actual number. DLT will not be observed in the dose expansion phase, and other research processes are the same as the dose increment phase. Researchers and collaborators will continue to monitor the safety data of the whole dose expansion phase and make decisions on admission and exit when necessary.
Interventions
OTHERCAR-T Therapy
CT1195E cells infusion
Sponsors
CARsgen Therapeutics Co., Ltd.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Voluntary signing of Informed Consent Form (ICF): I fully understand and am informed of this study, and I have signed the Informed Consent Form, expressing my willingness to follow and complete all research procedures; * When signing the ICF, the age should be between 18 and 65 years old (inclusive), with no gender restrictions; * No systemic active infection (such as infectious pneumonia, tuberculosis) within 2 weeks before screening; * Females with fertility (defined as all females who are physiologically capable of becoming pregnant) must agree to use highly effective contraception from at least 28 days before the start of self-cleaning to 1 year after CT1195E infusion, and absolutely prohibit egg donation within 1 year after receiving study treatment during the study period. Their male partners with fertility must agree to use effective barrier contraception from the start of self-cleaning to 1 year after CT1195E infusion, and should not donate semen or sperm during the entire study period; * Females with fertility must have a negative serum beta-human chorionic gonadotropin (β-hCG) test result at screening and within 48 hours prior to the initiation of chemotherapy. * Meet the EULAR/ACR 2019 classification criteria for SLE, with a disease history of ≥6 months; * Prior to screening, patients must have received treatment with glucocorticoids combined with immunosuppressants (including cyclophosphamide, mycophenolate mofetil, tacrolimus, methotrexate, cyclosporine, leflunomide) and/or biologics for ≥3 months, with a stable dosage for ≥2 weeks, and the disease must still be in an active state. During screening, oral steroids must meet the following requirements: If treated with hormone therapy alone, prednisone (or equivalent medication) should be ≥7.5 mg/day; When used in combination with immunosuppressants and/or biologics, there is no minimum daily dosage requirement for steroids; * During screening, positive for antinuclear antibody, and/or positive for anti-ds-DNA antibody, and/or positive for anti-Smith antibody; * During the screening period, patients with a SLEDAI-2K score of ≥7, or those with concurrent significant organ dysfunction, such as severe immune-mediated thrombocytopenia, lupus nephritis (histologically diagnosed as active nephritis type III or IV with or without type V); * During screening, involvement of active organs (including kidneys, heart and lungs, musculoskeletal system, blood system, blood vessels, etc.; involvement of skin and mucous membranes alone is not included) is present; * Adequate organ function: 1. Renal function: defined as creatinine clearance rate (Cockcroft-Gault) calculated without hydration assistance ≥ 50 mL/min; 2. Bone marrow function: defined as absolute neutrophil count (ANC) ≥1.0×10\^9/L and hemoglobin (Hb) ≥60 g/L. During the 7 days prior to screening for inclusion and
Exclusion criteria
, blood transfusions and growth factors must not be used to meet these requirements; 3. Liver function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2× upper limit of normal (ULN), and total bilirubin levels ≤2× upper limit of normal (ULN) 4. Coagulation function: defined as an international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN; 5. Lung function: When exposed to indoor air, the blood oxygen saturation (SpO2) is ≥92% (measured by a pulse oximeter); 6. Cardiac function: defined as having a left ventricular ejection fraction (LVEF) of ≥50% as assessed by echocardiography (ECHO) within the 8 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the maximum tolerable dose (MTD) and/or dose range of ct1195E | After medication to day 28 | Ct1195E MTD and/or dose range |
| severity of dose limiting toxicity (DLT) | Within 28 days after infusion | — |
| Incidence of dose limiting toxicity (DLT) | Within 28 days after infusion | — |
| severity of adverse events (AES) | Within 180 days after infusion | — |
| Incidence of adverse events (AES) | Within 180 days after infusion | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| After treatment, the index of lupus erythematosus assessment group (bilag-2004) changed from baseline | 1, 2, 3, 9 and 12 months after drug use | The minimum value of the British Isle lupus rating group index (bilag-2004) is 0 and the maximum value is 100. The higher the score, the higher the disease activity, that is, the more serious the disease. |
| The SLE activity score (sle-das) changed from baseline after treatment | 1, 2, 3, 9 and 12 months after drug use | The minimum value of sle-das score (systemic lupus erythematosus disease activity score) is 0, and the maximum value is usually 100. This score quantifies the disease activity by accumulating the scores of clinical and laboratory indicators. The higher the score, the stronger the disease activity and the more serious the disease. |
| Changes in clinicians' overall judgment (PGA) score from baseline after medication | 1, 2, 3, 9 and 12 months after drug use | In systemic lupus erythematosus (SLE), the minimum value of the doctors' global assessment (PGA) score is 0, and the maximum value is 3, where 0 indicates no disease activity and 3 indicates the most serious disease activity. The higher the score, the higher the disease activity, that is, the worse the result; Conversely, the lower the score, the lower the disease activity, and the better the result. |
| Proportion of patients without other SLE therapy after medication | 1, 2, 3, 9 and 12 months after drug use | — |
| Proportion of participants with SLE responder index (sri-4) | 1, 2,3, 6, 9 and 12 months after drug use | Preliminary evaluation of the efficacy of ct1195E in the treatment of moderate to severe refractory SLE.Proportion of participants who reached SLE responder index (sri-4) at 6 months and other time points (1, 2,3, 9 and 12 months after medication) |
| The change value of post medication Health Assessment Questionnaire Disability Index (HAQ-DI) from baseline | 1, 2, 3, 9 and 12 months after drug use | The minimum possible score of patients with systemic lupus erythematosus (SLE) using the Health Assessment Questionnaire Disability Index (HAQ-DI) is 0, and the maximum possible score is 3; The higher the score, the more severe the dysfunction of the patient, that is, the worse the outcome. |
| duration of ct1195E gene in blood | Within 1 year after CAR-T cell infusion | Objective to evaluate the cell kinetics of ct1195E in SLE participants, and to observe the level and duration of ct1195E gene copy number in blood. |
| Copy numbe of ct1195E gene in blood | Within 1 year after CAR-T cell infusion | Objective to evaluate the cell kinetics of ct1195E in SLE participants, and to observe the level and duration of ct1195E gene copy number in blood. |
| Changes of B cell functional subsets (initial B cells, memory B cells, plasma cells) after ct1195E infusion | Within 1 year after CAR-T cell infusion | Evaluate the efficacy (PD) characteristics of CT1195E in SLE participants. Changes in the levels of B cell functional subgroups (initial B cells, memory B cells, plasma cells) after CT1195E infusion. |
| Changes in immunoglobulin (IgG, IgM, IgA) levels during medication | 1, 2, 3, 9 and 12 months after drug use | — |
| Proportion of participants with low lupus disease activity status (lldas) | 1, 2,3, 6, 9 and 12 months after drug use | To evaluate the efficacy of ct1195E in the treatment of moderate to severe refractory SLE. The proportion of participants who reached lupus low disease activity status (lldas) at 6 months and other time points (1, 2, 3, 9 and 12 months after medication). |
| Proportion of participants achieving disease remission (doris) | 1, 2, 3, 6, 9 and 12 months after drug use | To evaluate the efficacy of ct1195E in the treatment of moderate to severe refractory SLE. The proportion of participants who achieved disease remission (doris) at 6 months and other time points ((1, 2, 3, 9 and 12 months after medication). |
| Changes of SLE disease activity index (sledai-2k) score from baseline after medication | 1,2,3,6,9 and 12 months after drug use | The score range of the Health Assessment Questionnaire Disability Index (HAQ-DI) is usually 0 to 3, where 0 represents no disability or intact function, and 3 represents severe disability or complete loss of function. The higher the score, the worse the functional status of the patient, that is, the higher the degree of disability; Conversely, the lower the score, the better the function. |
| After treatment, the SLE disease activity index (Selena - SLEDAI) score changed from baseline | 1, 2, 3, 6, 9 and 12 months after drug use | The minimum value of selena-sledai score is 0 points, and the maximum value can reach 105 points theoretically, but in actual clinical practice, 10 to 15 points usually indicate the presence of disease activity. Higher scores indicate higher disease activity rather than better outcomes. The score is used to quantify the activity of systemic lupus erythematosus (SLE). An increase in the score reflects a more active condition, which requires active clinical intervention; Conversely, a reduced score indicates good disease control. |
Countries
China
Contacts
Primary ContactQiubai Li
Outcome results
None listed