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.

抽象的 镰状细胞疾病（SCD）在美国影响大约100,000人 全球数百万。症状出生后不久出现，在不太发达国家 大多数SCD儿童在五岁之前死亡。在美国，SCD患者遭受慢性病 疼痛和疲劳，严重的急性疼痛危机需要住院和鸦片，中风和 多器官损坏，并在40多岁时具有平均死亡率。唯一获得FDA批准的药物 对于患有SCD的成年人是抗癌药羟基脲。迫切需要新的治疗 对于患有SCD的儿童和成人。 SCD-101是一种植物药，在体外表现出直接的体外和体内抗sick脚 活动。我们的目标是开发SCD-101作为一种安全有效的口服治疗，以防止 儿童和成人镰状细胞疾病的不可阻碍。在撒哈拉以南非洲和 印度，有数百万人患有镰状细胞疾病，80％的人口取决于 用于初级卫生保健的传统医学（植物医学）。因此，SCD-101作为植物学 药物是全世界数百万镰状细胞疾病的解决方案。 我们最近完成了28天的重复口服剂量，SCD-101的剂量降低研究 23个患有镰状细胞病的成年人。 1B期结果表明，SCD-101是安全的，并且 良好的耐受性并确定了在第二阶段研究中使用的剂量和时间表。在两个 最高剂量，对减轻疲劳和疼痛产生了深远的影响，这两个最常见 SCD的症状。在我们的1B期研究结果的基础上，我们提出了双盲 安慰剂控制的2x2跨界研究对18例纯合（S/S）镰状细胞病患者 建立在第2阶段和第3阶段研究中使用的临床相关终点。 一项跨界研究，每个主题都是他自己的控制，使有效的有效 样本量，因此，跨界研究具有36患者平行设计的等效功率。 拟议的跨界研究具有足够的能力，可以显示具有统计学意义的 基于我们的1B期结果，临床相关的疲劳改善，并可能显示出 疼痛的统计学意义和临床相关的改善。跨界研究也将 测量SCD-101对睡眠，红细胞（RBC）溶血标记，炎症的影响 细胞因子和静脉全血中循环镰状细胞。