Neuromyelitis Optica Spectrum Disease (NMOSD)
Conditions
Keywords
Neuromyelitis Optica Spectrum Disorders
Brief summary
KSVCBD injection is an in vivo Chimeric Antigen Receptor T-Cell (CAR-T cell) therapy product. This is a multi-center, single-arm, open-label, early exploratory clinical study. The objective of this study is to evaluate the safety and preliminary efficacy of KSVCBD injection in AQP4-positive Neuromyelitis Optica Spectrum Disorder
Detailed description
KSVCBD-R103 is an open-label study in subjects with NMOSD. The dose-escalation will be conducted to evaluate the safety and preliminary efficacy of KSVCBD. This study consists of a screening period, a treatment period and a follow-up period. During treatment period, the subjects will receive single-dose of KSVCBD injection. The duration of participation for each subject will be approximately 104 weeks.
Interventions
BIOLOGICALKSVCBD injection
KSVCBD injection is a CD19/BCMA-targeted in vivo-edited CAR-T cell injection. Three dose levels are predefined, and KSVCBD will be dose-escalated per the protocol-specified doses.
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
Key Inclusion Criteria: 1. Patients must meet the 2015 International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) and test positive for AQP4 antibodies. 2. Documented evidence of at least 1 relapse within 12 months before signing the informed consent form. 3. The Expanded Disability Status Scale (EDSS) score ≤ 8. 4. Female participants of childbearing potential must present a negative pregnancy test at screening and agree to use effective contraception throughout the study period. 5. Informed consent must be obtained from the patient or their legal representative, with a signed consent form must be provided. Key
Exclusion criteria
1. Viral infections: Known HIV, active HBV, or active HCV. 2. Pregnant or breastfeeding women. 3. History of other autoimmune diseases requiring immunosuppressive therapy. 4. Use of any live vaccines against infectious disease within 6 weeks before enrollment. 5. History of bone marrow/hematopoietic stem cell or solid organ transplantation. 6. Patients deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | Within 28 days post-infusion | DLT is defined as any of the predefined adverse events (AEs) related to KSVCBD 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 | AESI including grade ≥3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and infections |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ARR | Within 24 months post-infusion | Annualized relapse rate (ARR), Time to first relapse, and annualized hospitalization frequency after treatment. |
| Number of Active lesions | Within 24 months post-infusion | Change from baseline in the total number of active lesions on MRI after treatment; |
| EDSS score | Within 24 months post-infusion | Change from baseline in EDSS score |
| AQP4 antibody | Within 24 months post-infusion | Change from baseline in aquaporin-4 (AQP4) antibody level |
| Visual status | Within 24 months post-infusion | Change from baseline in visual acuity, visual field, and optical coherence tomography \[OCT, including retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL)\] after treatment. |
| KSVCBD lentiviral particle concentration | Within 24 months post-infusion | KSVCBD lentiviral particle concentration in peripheral blood. |
| CAR-positive T cells | Within 24 months post-infusion | CAR-positive T cells in peripheral blood. |
| CAR gene copy number | Within 24 months post-infusion | CAR gene copy number in peripheral blood |
| Number of CD19-positive cells | Within 24 months post-infusion | Number of CD19-positive cells in peripheral blood. |
| Number of BCMA-positive cells | Within 24 months post-infusion | Number of BCMA-positive cells in peripheral blood |
Countries
China
Contacts
CONTACTShihui Wei, MD
Outcome results
None listed