Safety Studies for Clinical Trials of a Botanical Drug for Sickle Cell Disease

镰状细胞病植物药临床试验的安全性研究

基本信息

批准号：
9052235
负责人：
Robert Swift
金额：
$ 80.74万
依托单位：
INVENUX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9052235
关键词：
Address Adult Adverse effects Affect Age Ames Assay Analgesics Anemia Animals Antineoplastic Agents Applications Grants Bilirubin Blood Blood Vessels Blood flow Bone Marrow Transplantation Botanicals Caring Cattle Cell Shape Cessation of life Child Chronic Clinical Clinical Trials Coupled Data Developing Countries Development Direct Costs Disease Disease Progression Dose Drug usage Effectiveness Embryonic and Fetal Development Erythrocytes FDA approved Folic Acid Funding Genes Goals Grant Hemoglobin Hereditary Disease Human Hyperviscosity Hypoxia In Vitro Infection Infection prevention Influenza vaccination Inherited Iron Overload Left Life Liquid substance Marketing Medical Medical Care Costs Monitor Morbidity - disease rate Mutation Neurocognitive Nitrogen No-Observed-Adverse-Effect Level Oral Organ Organ failure Oryctolagus cuniculus Pain Participant Pathogenesis Patients Penicillins Persons Pharmaceutical Preparations Pharmacotherapy Phase Phase II Clinical Trials Phase III Clinical Trials Plant Leaves Polymers Price Primary Health Care Procedures Prophylactic treatment Quality of life Rattus Reaction Renal function Research Rodent Safety Sales Sickle Cell Sickle Cell Anemia Sickle Hemoglobin Signs and Symptoms Small Business Innovation Research Grant Sorghum Sorghum vulgare Spleen Stroke Supportive care Teratology Testing Therapeutic Agents Tissues Toxic effect Traditional Medicine Transfusion Translating United States Variant Work beta Globin cohort cost drug development flexibility hydroxyurea in vivo intravenous injection mortality novel therapeutics public health relevance safety study sickling success

项目摘要

DESCRIPTION (provided by applicant): New therapeutic agents are urgently needed for the treatment of sickle cell disease, the world's most common genetic disease. Our long-term goal is to develop a botanical drug (SCD- 101) for use in children and adults that slows or stops disease progression. Sickle cell disease affects approximately 100,000 people in the United States and millions worldwide. In the US, those with SCD have an average mortality in their 40s and an estimated aggregate cost of medical care in excess of $1.4 billion per year. In less developed countries, 80% of children with SCD die before the age of five. The only FDA approved disease-modifying drug for use in SCD is the anti-cancer drug hydroxyurea, which has serious side effects and is only approved for use in adults. Sickle cell disease results from a mutation in the β-globin gene (Hb S), a variant of Hb A, the common adult hemoglobin. When deoxygenated, Hb S polymerizes, forming long polymers that deform the biconcave red blood cells (RBCs) into rigid, adherent, sickle-shaped cells. The rigid sickled RBCs are easily trapped in the microvasculature, blocking blood flow to tissues and organs with resultant ischemic tissue damage. Best supportive therapies for SCD include folic acid for anemia, penicillin to prevent infections, pneumococcal and influenza vaccinations, pain medication, and intravenous injection of fluids. Chronic transfusion therapy can modify the course of the disease, but hyperviscosity, alloimmune reaction, infection, and iron overload are just a few of the complications of transfusion therapy. Bone marrow transplants can cure SCD, but the morbidity and mortality of the procedure, coupled with difficulty in finding a donor match and the cost of the procedure, leave this an uncommon treatment option. SCD-101 is being evaluated in a Phase 1B dose escalation trial in adults with sickle cell disease to obtain an initial safety profile and explore possible effective oral doses that inhibit RBCs from sickling. Early data shows that SCD-101 can inhibit RBC sickling in humans. To proceed to a Phase II clinical trial additional non-clinical studies are needed. This Phase II grant proposal is for funding the necessary non-clinical studies.

描述（由申请人提供）：镰状细胞病是世界上最常见的遗传病，迫切需要新的治疗药物。我们的长期目标是开发一种用于儿童和成人的植物药物（SCD-101）。镰状细胞病影响着美国约 100,000 人以及全球数百万人，估计 SCD 患者的平均死亡率为 40 多岁。每年的医疗费用总计超过 14 亿美元，在欠发达国家，80% 的 SCD 儿童在五岁之前死亡，FDA 批准的唯一用于治疗 SCD 的疾病缓解药物是抗癌药物羟基脲。，它具有严重的副作用，仅被批准用于成人镰状细胞病是由 β-珠蛋白基因 (Hb S) 突变引起的，β-珠蛋白基因是 Hb A（常见的成人血红蛋白）的一种变体。脱氧后，Hb S 聚合，形成长聚合物，使双凹红细胞 (RBC) 变形为坚硬、粘附的镰状细胞，坚硬的镰状红细胞很容易被困在微血管中，阻碍血液流向组织和器官，从而导致缺血。 SCD 的最佳支持疗法包括叶酸治疗贫血、青霉素预防感染、肺炎球菌和流感疫苗接种、止痛药和静脉注射。慢性输血治疗可以改变疾病的病程，但高粘滞血症、同种免疫反应、感染和铁超负荷只是输血治疗的一些并发症，但骨髓移植可以治愈 SCD，但其发病率和死亡率较高。加上难以找到匹配的捐赠者以及手术费用，这使得 SCD-101 成为一种不常见的治疗选择，目前正在镰状细胞成人患者的 1B 期剂量递增试验中进行评估。疾病以获得初步安全性概况并探索可能有效的口服剂量可抑制红细胞镰状化。早期数据表明，SCD-101 可以抑制人类红细胞镰状化。为了进行 II 期临床试验，需要进行额外的非临床研究。非临床研究。