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Comparing and Combining Bortezomib and Mycophenolate in SSc Pulmonary Fibrosis

比较和联合硼替佐米和霉酚酸酯治疗 SSc 肺纤维化

基本信息

批准号：
8822628
负责人：
MANU JAIN
金额：
$ 21.42万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-15 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8822628
关键词：
Adverse event Alveolar Animal Model Anti-Inflammatory Agents Anti-inflammatory Asbestos Autoimmune Diseases Bleomycin Bortezomib Cause of Death Chest Chronic Clinical Data Clinical Management Clinical Trials Connective Tissue Diseases Cyclophosphamide Data Degradation Pathway Disease Disease Progression Dropout FDA approved Fibroblasts Fibrosis Frequencies Functional disorder Gene Expression Grant Hamman-Rich syndrome In Vitro Inflammation Injury Interstitial Lung Diseases Kidney Liquid substance Liver Fibrosis Lung Lung diseases Medicine Morbidity - disease rate Multiple Myeloma Mus Mycophenolate Myelofibrosis Normal tissue morphology Organ Pathogenesis Patients Pharmaceutical Preparations Phase III Clinical Trials Pilot Projects Placebos Population Prevalence Proteins Publishing Pulmonary Fibrosis Pulmonary Hypertension Randomized Rare Diseases Recording of previous events Research Research Personnel Safety Scleroderma Severe Adverse Event Skin Staging Subgroup Systemic Scleroderma Testing Tissues Toxic effect Transforming Growth Factors Ubiquitin Vital capacity animal data base cohort design effective therapy experience high risk immune activation inhibitor/antagonist innovation lung injury mortality mycophenolate mofetil novel pilot trial pre-clinical prevent programs protein degradation public health relevance therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disease with an estimated prevalence as high as 75 per 100,000. Pulmonary fibrosis occurs in ~40% of patients and is the leading cause of death while skin fibrosis is a significant cause of morbidity. There are no therapies that have shown a sustained effect in SSc associated pulmonary and skin fibrosis. Nevertheless, mycophenoalate mofetil (MMF) has become 1st line therapy at many SSc centers. Our published data shows that bortezomib, an FDA approved proteasomal inhibitor for the treatment of multiple myeloma, administered 7 or 14 days after the induction of lung injury by bleomycin prevented lung and skin fibrosis. Bortezomib has been used in more than 350,000 multiple myeloma patients worldwide with acceptable toxicity and tolerability. There is, however, no such data for bortezomib in SSc patients. Our in vitro and animal data provide a compelling pathophysiologic rationale for testing bortezomib for pulmonary and skin fibrosis. Thus in this grant we propose a pilot clinical trial of adding bortezomib to mycophenolate mofeteil (MMF) in patients with SSc Pulmonary Fibrosis. The objective of the trial is to assess safety, tolerability & efficacy of bortezomib in combination wih MMF in SSc patients at high risk of pulmonary disease progression.

描述（由申请人提供）：系统性硬化症（SSc）是一种慢性、多系统结缔组织疾病，估计患病率高达75/100，000。肺纤维化发生在约40%的患者中，并且是死亡的主要原因，而皮肤纤维化是发病的重要原因。没有治疗显示出对SSc相关的肺和皮肤纤维化的持续作用。然而，霉酚酸酯（MMF）已成为许多SSc中心的一线治疗。我们已发表的数据显示，博来霉素诱导肺损伤后7或14天给予硼替佐米（FDA批准用于治疗多发性骨髓瘤的蛋白酶体抑制剂）可预防肺和皮肤纤维化。硼替佐米已用于全球超过350，000例多发性骨髓瘤患者，毒性和耐受性可接受。然而，在SSc患者中没有硼替佐米的此类数据。我们的体外和动物数据为检测硼替佐米治疗肺和皮肤纤维化提供了令人信服的病理生理学依据。因此，在这项资助中，我们提出了一项试点临床试验，在SSc肺纤维化患者中将硼替佐米加入吗替麦考酚酯（MMF）。该试验的目的是评估硼替佐米与MMF联合治疗肺部疾病进展高风险的SSc患者的安全性、耐受性和疗效。