The goal of this clinical trial is to find out if the investigational medicine BMS-986353 is safe and well tolerated in adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a long-term autoimmune condition that affects the optic nerves and spinal cord and can lead to relapses. Most people with NMOSD have antibodies against AQP4, which are linked to future disease activity.
The main questions this study aims to answer are:
"-" Is CC-97540 (BMS-986353) safe and well tolerated, based on how many participants experience serious side effects that limit dosing (called dose-limiting toxicities)?
"-" Does CC-97540 (BMS-986353) show early signs of benefit, based on how many participants no longer have detectable AQP4 antibodies in their blood (called sero-reversion)?
Participants are adults aged 18 to 60 years with AQP4 antibody-positive NMOSD who are currently clinically stable on ravulizumab or satralizumab. Approved NMOSD treatments reduce relapses by changing how the immune system works, but they do not remove the cells that make AQP4 antibodies. This study is designed to see whether BMS-986353 can target these cells without the need for long-term immune suppression.
Participants will:
"-" Receive CC-97540 (BMS-986353) as part of the study "-" Continue their current NMOSD therapy "-" Attend study visits for safety checks, exams, and lab tests
Signed written informed consent
Age 18 to 60 inclusive
Diagnosis of anti-AQP4 antibody positive NMOSD by 2015 Wingerchuk IPND criteria
No relapses within last 12 months
History of active meningococcal disease
Presence of active, clinically significant concomitant CNS pathology, other than NMOSD, that may confound the ability to interpret study results, including but not limited to, seizure disorder, traumatic brain injuries, delirium, Parkinson's disease, psychosis, Neuro-Behcet's disease, Guillain-Barré syndrome, metabolic or infectious cause of myelopathy, genetically-inherited progressive CNS disorder, ischemic cerebrovascular disorders, including, but not limited to, transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage; CNS sarcoidosis; history of anti- myelin oligodendrocyte glycoprotein antibody-associated disorder or a diagnosis of progressive multifocal leukoencephalopathy (PML) or history of PML; or of infectious or autoimmune encephalitis or meningitis under prior DMT.
Any significant medical condition, laboratory test abnormality or psychiatric Active infection requiring treatment
Hypersensitivity or allergy to fludarabine, cyclophosphamide, excipients of CC- 97540, ravulizumab, tocilizumab or satralizumab.
Sequential
CC-97540 (BMS-986353)
Biological/VaccineCD19 CAR T therapy
Fludarabine
DrugLymphodepleting Chemotherapy
Cyclophosphamide
DrugLymphodepleting Chemotherapy
Tocilizumab
Drugmanagement of CRS
To evaluate the safety and tolerability of CC-97540 (BMS-986353) in participants with anti-AQP4 antibody positive NMO as determined by the proportion of patients experiencing DLTs
Proportion of patients experiencing DLTs at 4, 12 and 52 weeks post- infusion with CC-97540 (BMS-986353)
To evaluate the preliminary efficacy of CC-97540 (BMS-986353) in participants with anti-AQP4 antibody positive NMO as determined by the proportion of patients who sero-revert.
Proportion of patients seronegative for the anti-AQP4 antibody at 6 months post-infusion with treatment with CC-97540
Type, Frequency, and Severity of Treatment-Emergent Adverse Events
Adverse events will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, as follows: Grade 1: Mild adverse event Grade 2: Moderate adverse event Grade 3: Severe or medically significant but not immediately life-threatening Grade 4: Life-threatening consequences; urgent intervention indicated Grade 5: Death related to adverse event
To evaluate the preliminary efficacy of CC-97540 in participants with anti-AQP4 antibody positive NMO
Proportion of patients relapse free at 6, 12 and 18 months after infusion with CC-97540
Type, Frequency, and Severity of Treatment-Emergent Serious Adverse Events (SAEs)
To assess the proportion of patients relapse-free following discontinuation of background therapies
To assess the duration of sero-reversion over 12 months and duration of sero- negativity over 12 months
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University of Texas Southwestern Medical Center
Lead sponsor
Bristol-Myers Squibb
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
