Safety and Efficacy of BAFF-R CART for Refractory Neuroim... | NCT07022197

NCT07022197

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Participant Group BAFF-R CART cells	Experimental	Experimental: CART cells therapy，Dose level 1: 0.5 × 10^6 CART cells/Kg The tolerability and safety of BAFF-R CART cells will be assessed in an initial dose of 0.5×10^6 CART cells/Kg and three subjects will be enrolled firstly. Experimental: CART cells therapy，Dose level 2: 1 × 10^6 CART cells/Kg If neither DLT nor efficacy is shown in the first three subjects, the dose of CART cells will be increased to 1 × 10^6 CART cells/kg to assess DLT. Experimental: CART cells therapy，Dose level 3: 2 × 10^6 CART cells/Kg If DLT occurs in two subjects, whether to test the safety and efficacy in 2 × 10^6 CART cells/kg group will be determined by the investigator based on the initial data of efficacy, PK and PD.	Drug: BAFF-R CART

Interventions

Name	Type	Description	Arm Group Labels	Other Names
BAFF-R CART	Drug	Biological: BAFF-R CART cells Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to manufacture BAFF-R CART cells, during which cyclophosphamide will be administered for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with BAFF-R CART cells by intravenous (IV) infusion. The initial dose of 0.5×10^6 CART cells/kg will be infused on day 0. Drug: Cyclophosphamide and fludarabine Subjects will receive one 3-day cycle of lymphodepletion starting 4 days prior to BAFF-R CART cells infusion on Day 0. Subjects will be given IV infusion of cyclophosphamide 250 mg/m2/day on day -5, -4 and -3, and fludarabine 30 mg/m2 over 30 minutes administered immediately after cyclophosphamide.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Types and incidence of dose-limiting toxicity (DLT) after BAFF-R CART cells infusion	To evaluate the DLT occurred within 3 months after BAFF-R CART cells infusion.	Up to 3 months post BAFF-R CART cells infusion
Incidence and severity of AEs, including changes in vital signs, physical examination, laboratory parameters, Electrocardiograms and Echocardiograms.	To evaluate the AEs occurred within 2 years after BAFF-R CART cells infusion.	Up to 2 years post BAFF-R CART cells infusion

Secondary Outcomes

Measure	Description	Time Frame
PD-Soluble BAFF	The changes of concentration of soluble BAFF in the peripheral blood after BAFF-R CART cells infusion.	Up to 2 years post BAFF-R CART cells infusion
PD-Pathogenic antibody	The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid.

Other Outcomes

Measure	Description	Time Frame
NMOSD: the number of attacks	The number of attacks divided by observed year after BAFF-R CART cells infusion.	Up to 2 years post BAFF-R CART cells infusion
NMOSD: Accumulated total active MRI lesions

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

1. Assessed by the investigator as having a refractory neuroimmune disease;

Refractory neuroimmune diseases were defined as:

Poor symptom control on at least three immunosuppressive agents for more than one year;
Clinical evidence of at least two relapses within 12 months or three relapses within 24 months and one relapse within 12 months prior to screening.

2. Male study participants must agree to use contraception during the treatment period for 1 year after receiving study treatment, and sperm donation is prohibited throughout the study period;

3. In the case of females with childbearing potential, need to agree to use contraception during the treatment period and for at least 1 year after receiving study treatment. Participants must have a negative serum pregnancy test result at screening and a confirmed negative urine pregnancy test result prior to first CART treatment.

Exclusion Criteria:

Any medical or psychiatric condition that, in the opinion of the investigator, may jeopardize the study participant or affect the study participant's ability to participate in this study;
A history of drug or alcohol abuse within the 12 months prior to baseline, or any condition that in the opinion of the investigator is associated with poor adherence;
Women who are breastfeeding or pregnant, or who plan to become pregnant at any time during the 12-month time period following treatment with CART, or a history of spontaneous or induced abortion within 4 weeks prior to screening;
Study participants with a clinically relevant active infection (e.g., sepsis, pneumonia, or abscess) or serious infection (resulting in hospitalization or requiring antibiotic therapy) within 4 weeks prior to baseline;
The study participant has received a live attenuated vaccination within 8 weeks prior to baseline; or is scheduled to receive a live vaccination (including COVID-19 vaccine) within 8 weeks after treatment;
Study participants who have received prior treatment with rituximab within 6 months prior to baseline;
Study participants had received tolizumab, eculizumab within 3 months prior to baseline;
Study participants who have received intravenous human immunoglobulin, plasma exchange, undergone immunotherapy within 4 weeks prior to baseline;
Known concomitant serious underlying diseases, such as hepatic and renal impairment, hematologic disorders, previous severe cardiovascular disease, severe hypertension, diabetes mellitus, poor control of blood pressure and blood glucose;
Comorbid mental illness, suicidal ideation (affirmative answer (yes) to question 4 or question 5 of the Colombian Suicide Severity Rating Scale (C-SSRS) indicating a suicide attempt within the last 6 months);
Any of the following laboratory abnormalities during the screening period (a repeat measurement may be taken during the screening period prior to randomization to confirm results); (1) Elevated liver enzymes: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN); (2) Total bilirubin > 1.5 times the ULN; (3) Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2; (4) CD19 + B cell count <40 cells/µL;
Presence of a history of tuberculosis infection, high risk of acquired tuberculosis infection;
known immunodeficiency diseases, including human immunodeficiency virus (HIV) infection;
Viral hepatitis B surface antigen (HBsAg) positivity during the screening period;
Receiving blood transfusion therapy 4 weeks prior to baseline or during the screening period;
Any other condition that the investigator deems inappropriate for participation in the study.

ID	Term
D020277	Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
D009471	Neuromyelitis Optica
D009157	Myasthenia Gravis
D009220	Myositis

ID	Term
D011129	Polyradiculoneuropathy
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases