Crossover Study of an Oral Treatment for Sickle Cell Disease

镰状细胞病口服治疗的交叉研究

• 批准号: 9347994
• 负责人: Robert Swift
• 金额: $ 22.5万
• 依托单位: INVENUX, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-03 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347994
• 关键词: Acute; Admission activity; Adult; Adverse event; Affect; Africa South of the Sahara; Age; American; Antineoplastic Agents; Bilirubin; Biological Markers; Birth; Bone Pain; Botanicals; Cessation of life; Child; Chronic; Clinical; Cross-Over Studies; Crossover Design; Data; Developing Countries; Disease; Dose; Double-Blind Method; Electrocardiogram; Erythrocytes; Evaluable Disease; Exposure to; FDA approved; Fatigue; Goals; Grant; Hematocrit procedure; Hematological Disease; Hemolysis; Hospitalization; In Vitro; India; Inflammation; Inflammatory; Inherited; Laboratories; Measurement; Measures; Medical; National Heart, Lung, and Blood Institute; Numeric Rating Scale; Opiates; Oral; Pain; Patients; Pharmaceutical Preparations; Phase; Physical activity; Placebo Control; Placebos; Population; Primary Health Care; Quality of life; Questionnaires; Randomized; Reporting; Research; Reticulocytes; Safety; Sample Size; Schedule; Serious Adverse Event; Sickle Cell; Sickle Cell Anemia; Side; Sleep; Sleep disturbances; Stroke; Symptoms; Testing; Thalassemia; Traditional Medicine; United States; Venous; Walking; Whole Blood; base; capsule; chronic pain; clinically relevant; common symptom; cost; cytokine; design; hydroxyurea; in vivo; mortality; multiorgan damage; phase 2 study; phase 3 study; prevent; success; treatment duration

ABSTRACT Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide. Symptoms appear shortly after birth, and in less developed countries the majority of children with SCD die before the age of five. In the U.S., SCD patients suffer chronic pain and fatigue, severe acute painful crises requiring hospitalization and opiates, strokes, and multi-organ damage, and have an average mortality in their 40s. The only FDA approved drug for adults with SCD is the anticancer drug hydroxyurea. New treatments are desperately needed for both children and adults with SCD. SCD-101 is a botanical drug that has shown direct in vitro and in vivo anti-sickling activity. Our goal is to develop SCD-101 as a safe and effective oral treatment that prevents the inexorable progression of sickle cell disease in children and adults. In sub-Saharan Africa and India, where many millions suffer with sickle cell disease, 80% of the population depends on Traditional Medicine (botanicals) for primary health care. Therefore, SCD-101, as a botanical drug, is the solution for the millions with sickle cell disease worldwide. We recently completed a 28-day repeat oral dose, dose-escalation study of SCD-101 in 23 adults with sickle cell disease. The Phase 1b results showed that SCD-101 was safe and well tolerated and established the dose and schedule to be used in a Phase 2 study. At the two highest doses, there was a profound effect on reducing fatigue and pain, the two most common symptoms of SCD. Building on the results of our Phase 1b study, we propose a double-blind, placebo controlled 2x2 crossover study in 18 patients with homozygous (S/S) sickle cell disease to establish the clinically relevant endpoints to be used in a Phase 2 and Phase 3 study. A crossover study, where each subject is his or her own control, doubles the effective sample size, so the crossover study has the equivalent power of a 36 patient parallel design. The proposed crossover study has sufficient power to show a statistically significant and clinically relevant improvement in fatigue based our Phase 1b results, and may show a statistically significant and clinically relevant improvement in pain. The crossover study will also measure the effect of SCD-101 on sleep, red blood cell (RBC) hemolysis markers, inflammatory cytokines, and circulating sickled cells in venous whole blood.

摘要 镰状细胞病(SCD)在美国影响大约10万人， 全球数百万人。症状在出生后不久就会出现，在欠发达国家 大多数患有SCD的儿童在5岁之前死亡。在美国，SCD患者患有慢性阻塞性肺疾病 疼痛和疲劳，严重的急性疼痛危机需要住院和鸦片类药物，中风和 多器官损害，平均死亡率在40多岁。FDA批准的唯一一种药物 对于患有SCD的成年人来说，羟基脲是一种抗癌药物。迫切需要新的治疗方法 对患有SCD的儿童和成人都适用。 SCD-101是一种植物类药物，已在体外和体内显示出直接的抗病作用。 活动。我们的目标是开发SCD-101作为一种安全有效的口腔治疗方法，以防止 镰状细胞病在儿童和成人中的不可避免的发展。在撒哈拉以南非洲和 在印度，数百万人患有镰状细胞病，80%的人口依赖于 初级卫生保健的传统医学(植物药)。因此，SCD-101作为一种植物学 药物是全球数百万镰状细胞疾病的解决方案。 我们最近完成了一项为期28天的SCD-101重复口服剂量-剂量-递增研究 23例成人镰状细胞病。1b期试验结果表明，SCD-101是安全的 耐受性良好，并确定了在第二阶段研究中使用的剂量和时间表。在这两个 最高剂量，对减少疲劳和疼痛有深远的效果，这两种最常见的 SCD的症状。基于我们1b阶段研究的结果，我们提出了一个双盲、 18例S/S纯合子镰状细胞病患者的安慰剂对照2x2交叉研究 建立在2期和3期研究中使用的临床相关终点。 交叉研究，其中每个受试者都是他或她自己的对照，使有效率加倍 样本量，所以交叉研究具有36名患者平行设计的等效性。 拟议的交叉研究具有足够的力量来显示统计上显著的和 根据我们的1b期结果，疲劳的临床相关改善，并可能显示 疼痛改善具有统计学意义和临床相关性。交叉研究还将 测定SCD-101对睡眠、红细胞溶血标志物、炎症反应的影响 细胞因子和静脉全血中的循环镰状细胞。