Crossover Study of an Oral Treatment for Sickle Cell Disease

镰状细胞病口服治疗的交叉研究

基本信息

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
项目类别：
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

项目摘要

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.

抽象的镰状细胞病 (SCD) 影响美国约 100,000 人全球数以百万计。症状在出生后不久出现，在欠发达国家大多数患有 SCD 的儿童在五岁之前死亡。在美国，SCD 患者患有慢性疾病疼痛和疲劳、需要住院和服用阿片类药物的严重急性疼痛危机、中风和多器官损伤，平均死亡率为 40 多岁。 FDA唯一批准的药物对于患有 SCD 的成人来说，抗癌药物是羟基脲。迫切需要新的治疗方法适用于患有 SCD 的儿童和成人。 SCD-101是一种植物药物，在体外和体内表现出直接的抗镰状化作用活动。我们的目标是开发 SCD-101 作为一种安全有效的口服治疗药物，预防儿童和成人镰状细胞病的不可避免的进展。在撒哈拉以南非洲和印度有数百万人患有镰状细胞病，80% 的人口依赖用于初级卫生保健的传统医学（植物药）。因此，SCD-101作为一种植物药药物，是全球数百万镰状细胞病患者的解决方案。我们最近完成了一项 SCD-101 的 28 天重复口服剂量、剂量递增研究 23 名患有镰状细胞病的成年人。 1b 期结果表明 SCD-101 是安全的耐受性良好，并确定了 2 期研究中使用的剂量和时间表。在两个最高剂量，对减轻疲劳和疼痛有深远的影响，这两种最常见的症状 SCD 的症状。基于我们 1b 期研究的结果，我们提出了双盲、对 18 名纯合 (S/S) 镰状细胞病患者进行安慰剂对照 2x2 交叉研究确定用于 2 期和 3 期研究的临床相关终点。交叉研究，其中每个受试者都是他或她自己的控制者，使有效效果加倍样本量，因此交叉研究具有 36 名患者平行设计的等效功效。拟议的交叉研究有足够的能力来显示统计显着性和基于我们的 1b 期结果，临床相关的疲劳改善，可能会显示疼痛方面具有统计学显着性和临床相关性的改善。交叉研究还将测量 SCD-101 对睡眠、红细胞 (RBC) 溶血标志物、炎症的影响细胞因子和静脉全血中的循环镰状细胞。