Safety and Efficacy of BAFFR CART for Relapsed/ Refractory Neuromyelitis Optica Spectrum Disorder

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuromyelitis Optica Spectrum Disorder
• Intervention / Treatment: Drug: Anti-BAFFR CART

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participant Group; BAFFR CART cells	Drug: Anti-BAFFR CART; Anti-BAFFR CART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	Incidence of dose-limiting toxicity (DLT) will be evaluated within the first 28 days following BAFFR CART cells infusion.	Up to 28 days
Incidence and severity of adverse events	Adverse events will be evaluated following the chemotherapy preparative regimen and infusion of BAFFR CART cells within the first 28 days.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of BAFFR CART cells in peripheral blood	The proportion of BAFFR CART cells in peripheral blood will be detected after infusion.	Up to 1 years
Annualized relapse rate (ARR)	ARR is defined as the number of attacks divided by the total participant-years after infusion.	Up to 1 years
Changes of B cell levels in bone marrow and peripheral blood	The changes of B cell levels in bone marrow and peripheral blood after BAFFR CART infusion.	Up to 1 years
Changes of AQP4 antibody titers	Changes of AQP4 antibody titers from baseline over 1 year after BAFFR CART infusion.	Up to 1 years
Changes of cytokine in peripheral blood	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.	Up to 1 years
Changes of Expanded Disability Status Scale (EDSS) score	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.	Up to 1 years
Changes of visual acuity	Corrected visual acuity is determine by Snellen E chart held at a distance of 5 meters.	Up to 1 years
Accumulated total active MRI lesions	The changes of T2 lesions and/or enhancing T1 Lesions as detected by brain Magnetic Resonance Imaging (MRI).	Up to 1 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica
• Other Study ID Numbers: IRB2024-YX-220-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No