A Safety and Tolerability Study of CC- 97540 (BMS-086353) in Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Patients

Официальное название

A Multicenter, Phase 1, Safety and Tolerability Study of CC-97540 (BMS- 986353) in Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Patients

Обзор

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

Вмешательства

• Биопрепарат CC-97540 (BMS-986353)
  CD19 CAR T therapy
• Препарат Fludarabine
  Lymphodepleting Chemotherapy
• Препарат Cyclophosphamide
  Lymphodepleting Chemotherapy
• Препарат Tocilizumab
  management of CRS

Первичные конечные точки

• 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 [Срок оценки: From infusion to 52 weeks post-infusion]
• 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. [Срок оценки: From infusion to 6 months post-infusion]

Вторичные конечные точки (4)

• Type, Frequency, and Severity of Treatment-Emergent Adverse Events [Срок оценки: From infusion to 52 weeks post-infusion]
• To evaluate the preliminary efficacy of CC-97540 in participants with anti-AQP4 antibody positive NMO [Срок оценки: From treatment to 6 months post-treatment]
• Type, Frequency, and Severity of Treatment-Emergent Serious Adverse Events (SAEs) [Срок оценки: From infusion to 52 weeks post-infusion]
• To assess the proportion of patients relapse-free following discontinuation of background therapies [Срок оценки: From screening to 12 months post-infusion]

Критерии участия

Критерии включения

• Signed written informed consent

a. Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written ICF in accordance with regulatory, local, and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.

• Age 18 to 60 inclusive
• Diagnosis of anti-AQP4 antibody positive NMOSD by 2015 Wingerchuk IPND criteria
• No relapses within last 12 months
• Stable ravulizumab or satralizumab dosing for at least 6 months
• Up to date on meningococcal vaccines and enrolled in any required REMS program
• EDSS score of 6.5 or less
• At least one eye best visual acuity 20/200 or better
• Peripheral B cell count by flow cytometry of >5%
• Positive anti-AQP4 antibody test on cell based assay at screening
• Patient has adequate vascular access for leukapheresis
• ALT and AST <1.5x upper limit of normal

Критерии исключения

• 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.
• condition that would pose a risk the participant's safety from participating in the study.
• Active autoimmune condition other than NMOSD that requires immunotherapy
• History of any one of the following cardiovascular conditions within the 6 months prior to screening: Class III or IV heart failure as defined by the New York Heart Association, myocardial infarction, unstable angina, angioplasty or stenting, or other clinically significant cardiac disease.
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the investigator; or unwillingness or inability to follow the procedures required in the protocol.
• Prior history of malignancies or lymphoproliferative disease, unless the participant has been free of the disease for ≥ 2 years. The following are allowed:

• Basal or squamous cell carcinoma of the skin.
• Carcinoma in situ of the cervix or breast.
• Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system) or prostate cancer that is curative.
• Other completely resected Stage I solid tumor with low risk for recurrence.
• Active syphilis, any human immunodeficiency virus, human lymphocytic T-cell virus type 1 and/or type 2, or active or latent tuberculosis infection.
• Known chronic, active hepatitis B or C virus (HBV/HCV) infection or untreated prior HCV infection (positive HCV IgG result). Participants who had HCV but have received an antiviral treatment and show no detectable HCV viral RNA for 6 months are eligible. Participants with no active hepatitis B infection (eg, hepatitis B surface antigen \[HBsAg\] negative, anti-hepatitis B core antibody \[HBcAb\]positive) who are under adequate prophylaxis against HBV re-activation may be eligible; such participants must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels or viral load; those who are PCR positive will be excluded. Participants who have received HBV vaccine and are hepatitis B surface antibody (HBsAb) positive, HBcAb negative, and HBsAg negative are eligible for study entry.
• Uncontrolled or active systemic fungal, bacterial, viral, or other infection despite appropriate anti-infective treatment at the time of leukapheresis, or within 72hours before LD chemotherapy, or 5 days before CC-97540 (BMS-986353) administration.
• Use of any live vaccines against infectious disease within 6 weeks prior to the start of lymphodepleting therapy, during CC-97540 (BMS-986353) infusion, and until immune recovery.
• Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to leukapheresis or initiation of LD chemotherapy. Acute symptoms must have resolved and based on investigator assessment there are no sequelae that would place the participant at a higher risk of receiving study treatment.
• Any condition that confounds the ability to interpret data from the study.
• Participants who are not up to date on all recommended vaccinations per local/national Health Authority (eg, Centers for Disease Control and Prevention) or institutional guidelines for immunocompromised individuals. For vaccines requiring more than one dose, the full series (eg, both doses of a 2-dose series) should be completed prior to leukapheresis or initiation of LD chemotherapy when feasible and when a delay in leukapheresis or initiation of LD chemotherapy would not put the study participant at risk.
• An answer of "yes" to items 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening (for the past 6-months interval).
• Pregnancy or nursing women
• Prior CAR T therapy
• Stem cell transplantation within one year of screening
• Positive Quantiferon test
• Prisoners or participants who are involuntarily incarcerated.
• Contraindications against MRI imaging, including non-MRI compatible metal implants, cardiac pacemakers, cochlear implants, ventricular shunt systems; metal particles in the body that pose a risk to the participant, including large tattoos in regions affected by cranial/neck MRI scanning, and severe claustrophobia. Contraindications against gadolinium-based contrast agents, including known hypersensitivity to gadolinium-based contrast agents.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UT Southwestern — Dallas

Идентификаторы

NCT: NCT07573332 · CA061-1031

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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