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An Open Label Trial of Ixazomib for Treatment Resistant Myasthenia Gravis

Ixazomib 治疗难治性重症肌无力的开放标签试验

基本信息

批准号：
10645048
负责人：
HENRY J KAMINSKI
金额：
$ 15.79万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10645048
关键词：
Adverse effects Adverse event Antibodies Antibody Repertoire Antibody titer measurement Autoantibodies Autoimmune Diseases B-Cell Antigen Receptor B-Lymphocyte Subsets Biological Biological Monitoring Blood CD14 gene CD19 gene CD3 Antigens Cells Cholinergic Receptors Clinical Clinical Research Common Terminology Criteria for Adverse Events Development Dose Evaluation Generalized Myasthenia Gravis Hematology IgE Immunoglobulin A Immunoglobulin D Immunoglobulin G Immunoglobulin M Infusion procedures Investigation Laboratories Lymphocyte MS4A1 gene MUSK gene Malignant - descriptor Malignant Neoplasms Mature B-Lymphocyte Multiple Myeloma Muscle Muscle Weakness Myasthenia Gravis Oral Administration PTPRC gene Participant Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phase Phenotype Pilot Projects Plasma Plasma Cells Plasmablast Population Prednisone Proteasome Inhibition Proteasome Inhibitor RNA Splicing Radioimmunoprecipitation Assay Rare Diseases Research Project Grants Resistance Safety Serious Adverse Event Signal Transduction Time Transcript United States National Institutes of Health Vaccines Variant follow-up open label safety assessment

项目摘要

Myasthenia gravis (MG) is an autoimmune disorder characterized by muscle weakness caused by autoantibodies, mainly targeting the muscle acetylcholine receptor (AChR) and the muscle specific kinase (MuSK). These antibodies are produced by short-lived plasmablasts and long-lived plasma cells. To date, no MG treatment specifically targets either of these cells. Ixazomib is a proteasome inhibitor used successfully to treat multiple myeloma, a cancer of malignant plasma cells. We propose the IxMG trial to evaluate whether orally administered ixazomib will be safe and have biological and clinical signals of efficacy for patients with treatment-resistant AChR or MuSK MG, which comprise upwards of 30% of the MG population. Patients will be treated with 3 cycles of ixazomib (weekly infusions every week for 3 weeks) during a period of 3 months followed by 3 month follow-up. Clinical and biological monitoring will be performed at time of each treatment and then every 4 weeks. The trial will assess the safety, tolerability, and activity of ixazomib as a therapy for treatment-resistant patients with generalized myasthenia gravis and detailed autoantibody analysis, lymphocyte characterization, and antibody repertoire evaluation. A no-go decision for a Phase 2 assessment will be made for excess adverse effects or lack of target engagement, while a decision to proceed will be made based on safety and confirmation of biological target engagement.

重症肌无力（MG）是一种以肌肉无力为特征的自身免疫性疾病