A Study of C-CAR168 in the Treatment of Central Nervous System Autoimmune Diseases Refractory to Standard Therapy

Phase 1Not Yet RecruitingNCT07341828

Huashan Hospital15 enrolled

Overview

This is an investigator-initiated, single-center, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, for the treatment of adult patients with central nervous system autoimmune diseases refractory to standard therapy

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Sclerosis (MS)Neuromyelitis Optica Spectrum Disorders (NMOSD)Autoimmune Encephalitis Stiff Person Syndrome

Interventions

CD20/BCMA-directed CAR-T cellsBIOLOGICAL

Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 18 to 70 years old at the time of signing the Informed Consent Form (ICF). * Diagnosed as Multiple Sclerosis (MS)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Autoimmune Encephalitis(AiE)/Stiff Person Spectrum Disorder(SPSD) according to recognized diagnostic criteria for at least 6 months. * Prior treatment failure with standard therapy. * Adequate bone marrow, coagulation, cardiopulmonary, liver and renal function. Exclusion Criteria: * Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Treponema Pallidum (TP) positive, Cytomegalovirus (CMV) DNA positive, Epstein-Barr Virus (EBV) DNA positive. * Uncontrolled active infection. * Live vaccine injection within 4 weeks prior to signing the ICF. * Major organ transplantation history or bone marrow/hematopoietic stem cell transplantation history. * Severe cardiovascular diseases within the past 6 months prior to screening. * A history of ≥ Grade 2 bleeding within 4 weeks prior to screening, or requiring long-term anticoagulants treatment. * Inadequate washing time for previous treatment. * Previously treated with CAR-T cell products or genetically modified T cell therapies. * Pregnant or lactating women. * Severe central nervous system diseases or pathological changes. * Malignancy history within 5 years prior to signing the ICF. * Any contraindication to lumbar puncture.

Outcomes

Primary Outcomes

Incidence and severity of Adverse Events [Safety and Tolerability]

Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion

Time frame: Throughout the first 3 months follow up period completion

The subsequent recommended dose of C-CAR168 in patients with central nervous system autoimmune diseases refractory to standard therapy

Based on the assessment of overall safety profile

Time frame: Throughout the first 24 months follow up period completion

Secondary Outcomes

Incidence and severity of adverse events (AE)

Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study

Time frame: Throughout the first 24 months follow up period completion

MS: No Evidence of Disease Activity-3 (NEDA-3)

Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period

Time frame: Throughout the first 24 months follow up period completion

MS and NMOSD: Expanded Disability Status Scale (EDSS)

Change from baseline in EDSS at 6 months and 24 months post-infusion. EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death).

Time frame: Throughout the first 24 months follow up period completion

MS and NMOSD: MRI

Number of T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, as well as their change from baseline, at 6 months and 24 months post-infusion. Change from baseline in total T2 lesion volume, gray matter volume (GMV), white matter volume (WMV), and brain volume (BV), as well as annualized-brain volume loss (a-BVL), at 6 months and 24 months post-infusion

Central Contacts

Xiangjun Chen

CONTACT

+86 21 52888159 xiangjchen@fudan.edu.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.