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（由适用提供）：迫切需要新的治疗剂来治疗镰状细胞病，这是世界上最常见的遗传疾病。我们的长期目标是开发一种植物药（SCD-101），用于放慢或阻止疾病进展的儿童和成人。在美国，镰状细胞疾病影响着大约100,000人，在全球范围内数百万人。在美国，患有SCD的人在40多岁时平均死亡率，估计每年超过14亿美元的医疗服务总成本。在不太发达国家，有80％的SCD儿童在五岁之前死亡。唯一可以在SCD中使用的FDA批准的疾病改良药物是抗癌药物羟基脲，该药物具有严重的副作用，仅批准用于成人。镰状细胞疾病是由β-珠蛋白基因（HB S）突变引起的，β-珠蛋白基因（HB A）的变体是常见的成年血红蛋白。当脱氧时，HB S会聚合，形成长聚合物，使双孔红细胞（RBC）变形为刚性，坚固，镰状细胞。刚性镰刀式的RBC很容易被困在微脉管系统中，阻塞了组织和器官的血液流动，导致缺血组织损伤。 SCD的最佳支撑疗法包括用于贫血的叶酸，预防感染的青霉素，肺炎球菌和影响力疫苗的疫苗，止痛药以及液体静脉注射。慢性输血疗法可以改变疾病的病程，但是高管性，同种免疫反应，感染和铁超负荷只是输血疗法的一些并发症。骨髓移植可以治愈SCD，但是该手术的发病率和死亡率，再加上很难找到供体匹配和手术成本，这是一个罕见的治疗选择。在患有镰状细胞疾病的成年人的1B剂量升级试验中，正在评估SCD-101，以获得初始安全性并探索可能有效的口服剂量会抑制RBC的病。早期数据表明，SCD-101可以抑制人类的RBC疾病。为了进行II期临床试验，需要进行其他非临床研究。该第二阶段赠款提案是为了资助必要的非临床研究。