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