Autoimmune Diseases
Conditions
Keywords
Autoimmune Diseases, Immunotherapy
Brief summary
KSVCBD injection is an in vivo Chimeric Antigen Receptor T-Cell (CAR-T cell) therapy product. This single-arm, open-label, early exploratory clinical study is designed to evaluate the safety and preliminary efficacy of KSVCBD injection in patients with Autoimmune Diseases.
Detailed description
KSVCBD-R102 is an open-label study in subjects with autoimmune diseases and will be conducted in two stages: dose escalation (Stage A) and dose expansion (Stage B). In Stage A, a total of three dose levels explored. At the recommended dose established during the dose-escalation phase, subjects will be enrolled in a dose-expansion study to further evaluate the safety and preliminary efficacy of KSVCBD injection in subjects with autoimmune diseases. The dose-expansion study will explore two separate cohorts, each enrolling subject with an indication for which preliminary efficacy data have been obtained during the dose-escalation phase.
Interventions
DRUGKSVCBD injection
KSVCBD injection is an in vivo CAR-T therapy targeting CD19/BCMA and is administered by IV infusion.
Sponsors
Chinese PLA General Hospital
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
1. Age 18-65 years (inclusive), any gender. 2. Subjects diagnosed with the following autoimmune disease: moderate/severe refractory Systemic Lupus Erythematosus, elapsed/refractory Systemic Sclerosis, relapsed/refractory ANCA-Associated Vasculitis, refractory Idiopathic Inflammatory Myopathy, active Sjögren's Syndrome, chronic/refractory Immune Thrombocytopenia, refractory Antiphospholipid Syndrome, relapsed/refractory pemphigus, relapsed/refractory IgG4-Related Disease. 3. Having adequate organ function as required by the protocol.: 4. Voluntarily adhere to the contraception requirements as specified in the protocol. 5. Willing to comply with all study procedures and voluntarily participate in this study and sign the informed consent form (ICF).
Exclusion criteria
1. Previous or current active malignancy, including patients with cancer-associated polymyositis/dermatomyositis. Exceptions are cured or relapse-free for at least 3 years: cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer, locally advanced prostate cancer after radical treatment, or ductal carcinoma in situ after radical surgery. 2. Severe pulmonary disease within the past 1 year, such as moderate/severe pulmonary arterial hypertension (pulmonary artery systolic pressure \>50 mmHg on echocardiography), requirement for oxygen therapy via reservoir mask or non-invasive/invasive ventilator support at screening. 3. Use of any of the protocol specified drugs or treatments within the specified timeframes. 4. History or current symptoms of severe central nervous system (CNS) disease within the past 6 months. 5. Known severe allergy to the study drug or any of its components. 6. Presence of uncontrolled fungal, bacterial, or viral infection, or other infections considered by the investigator to make the subject unsuitable for participation. 7. History of major organ transplant or hematopoietic stem cell/bone marrow transplantation. 8. History of other autoimmune diseases requiring systemic treatment, other than the target indication. 9. History of non-IIM conditions such as drug induced myopathy, HIV associated myopathy, thyroid myopathy, or family history of myopathy. 10. Pregnant or breastfeeding women. 11. Use of any live vaccines within 6 weeks before enrollment. 12. Participation in another interventional clinical study and receipt of an active investigational drug within 3 months prior to signing the ICF, or intention to participate in another clinical trial or receive treatment for autoimmune diseases outside the protocol during the entire study period. 13. Psychiatric disorders with depression or suicidal tendencies. 14. Any other factors considered by the investigator to make the subject unsuitable for enrollment or to affect the subject's participation or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | Within 28 days post-infusion | DLT is defined as any of the following adverse events (AEs) related to KSVCBD infusion occurring within 28 days after KSVCBD infusion (CRS and ICANS will be graded according to the ASTCT 2019 criteria, and other AEs will be evaluated using CTCAE v6.0). |
| Adverse events (AEs) and serious adverse events (SAEs) | Within 24 months post-infusion | Incidence and severity of AEs and SAEs |
| Adverse events of special interest (AESI) | Within 24 months post-infusion. | Incidence and severity of AESIs.AESI including grade ≥3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and infections. |
| Recommended Phase 2 Dose (RP2D) | Within 24 months post-infusion | — |
Countries
China
Contacts
CONTACTJian Zhu, M.D.
PRINCIPAL_INVESTIGATORJian Zhu
Rheumatology Department of Chinese PLA General Hospital
PRINCIPAL_INVESTIGATORWeidong Han
Biotherapeutic Department of Chinese PLA General Hospital
PRINCIPAL_INVESTIGATORYang Liu
Biotherapeutic Department of Chinese PLA General Hospital
Outcome results
None listed