Neuromyelitis Optica Spectrum Disorder
Conditions
Brief summary
This is an open-label, single-arm, dose-escalation study in up to 20 participants with relapsed/refractory Neuromyelitis Optica Spectrum Disorders (NMOSD). The aim is to evaluate the safety and efficacy of the treatment with BAFFR CART.
Interventions
DRUGAnti-BAFFR CART
Anti-BAFFR CART
Sponsors
Tianjin Medical University General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects aged 18-60 years; 2. Patients must be diagnosed as AQP4-IgG-positive NMOSD; 3. At least one immunosuppressant has been used for over a year with poorly controlled symptoms; 4. Clinical evidence of at least two relapses in the last 12 months or three relapses in the last 24 months and one relapse in the preceding 12 months before screening. 5. Subjects and their partners must be willing to use effective and reliable methods of contraception, devices or medicines, within one year before BAFFR CART cells infusion. 6. Subjects must provide written informed consent before the study begins and comply with the requirements of the study protocol.
Exclusion criteria
1. Subjects have received B cell deletion treatment within 6 months before screening; 2. Chronic and active hepatitis B (HBV), hepatitis C (HCV), Human Immunodeficiency Virus (HIV) infection, CMV or syphilis infections concurrently. 3. Subjects with Papovaviruses infection. 4. Subjects have received live attenuated vaccine vaccination within 8 weeks before screening; or plan to receive live vaccine vaccination within 8 weeks after treatment; 5. History of psychoactive drug abuse and failed to withdraw, or have a history of psychiatric disorders. 6. Pregnant or lactating women. 7. Subjects with severe heart, liver, kidney or bone marrow function disorder. 8. Allergic constitution or a history of severe allergies. 9. Subjects with conditions adjudicated by the investigator as unsuitable for lymphodepletion or cell infusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity (DLT) | Up to 28 days | Incidence of dose-limiting toxicity (DLT) will be evaluated within the first 28 days following BAFFR CART cells infusion. |
| Incidence and severity of adverse events | Up to 28 days | Adverse events will be evaluated following the chemotherapy preparative regimen and infusion of BAFFR CART cells within the first 28 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of B cell levels in bone marrow and peripheral blood | Up to 1 years | The changes of B cell levels in bone marrow and peripheral blood after BAFFR CART infusion. |
| Changes of AQP4 antibody titers | Up to 1 years | Changes of AQP4 antibody titers from baseline over 1 year after BAFFR CART infusion. |
| Changes of cytokine in peripheral blood | Up to 1 years | Changes of cytokine(including IL-6, IFN-γ, TNF-α, and serum BAFF) in peripheral blood from baseline over 1 year after BAFFR CART infusion. |
| Proportion of BAFFR CART cells in peripheral blood | Up to 1 years | The proportion of BAFFR CART cells in peripheral blood will be detected after infusion. |
| Changes of visual acuity | Up to 1 years | Corrected visual acuity is determine by Snellen E chart held at a distance of 5 meters. |
| Accumulated total active MRI lesions | Up to 1 years | The changes of T2 lesions and/or enhancing T1 Lesions as detected by brain Magnetic Resonance Imaging (MRI). |
| Changes of Expanded Disability Status Scale (EDSS) score | Up to 1 years | Participant will be considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more. |
| Annualized relapse rate (ARR) | Up to 1 years | ARR is defined as the number of attacks divided by the total participant-years after infusion. |
Outcome results
None listed