PHASE I/II SAFETY, PHARMACOKINETIC, AND PHARMACODYNAMIC STUDY OF SARGRAMOSTIM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。克罗恩病是炎症性肠病（IBD）中最常见的类型。在最近的一项荟萃分析中，北美的克罗恩病患者人数估计在40万至60万之间。虽然这种疾病可以影响任何年龄组，但最常见于15至35岁的年轻人，平均发病年龄为22至23岁。总体而言，人群中约25%的新病例发生在20岁以下的个体中。大多数儿科病例在10至19岁之间被诊断;婴儿和幼儿的克罗恩病发生频率较低。克罗恩病是一种严重的终身疾病。其特征为透壁性，通常为肉芽肿性炎症，可导致粘膜溃疡、肠狭窄和瘘管形成。在许多儿童克罗恩病病例中，起病隐匿，伴有非特异性胃肠道（GI）症状或肠外表现，导致诊断延迟或不正确。该病最常见的症状包括腹泻、腹痛、发烧和体重减轻。与小肠受累或上消化道受累相关的症状包括餐后痉挛、早饱、恶心、厌食和腹泻。与成人一样，儿童克罗恩病的临床病程存在相当大的变异性。儿童克罗恩病的一般治疗原则反映了适用于成人的原则。然而，小儿克罗恩病的管理提出了更大的和独特的挑战，因为疾病对他们的生长，发育，生活质量，长期疾病相关并发症的影响，并在以后的生活中治疗的潜在后遗症。本研究的主要目的是在活动性克罗恩病儿科患者中，在第一个周期后和重复周期后（如果符合方案要求），描述沙格司亭治疗伴或不伴伴随皮质类固醇诱导治疗的安全性和临床效果。次要目的是：（1）描述沙格司亭治疗伴或不伴皮质类固醇儿童克罗恩病患者的药代动力学和药效学特性;和（2）评价沙格司亭治疗伴或不伴皮质类固醇儿童克罗恩病活动指数的疗效（PCDAI;缓解定义为降低大于或等于12.5分）、医生总体评估（PGA）和IMPACT-III问卷（≥ 10岁的患者）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Crohn's disease is the most common type of inflammatory bowel disease (IBD). In a recent meta-analysis, the number of Crohn's patients in North America is estimated to be between 400,000 and 600,000. While the disease can affect any age group, it is most commonly diagnosed in young adults between the ages of 15 and 35, with average age at onset of 22 to 23 years. Overall, approximately 25% of new cases in the population occur in individuals below 20 years of age. Most pediatric cases are diagnosed between the ages of 10 and 19 years; Crohn's disease in infants and young children occur less frequently. Crohn's disease is a serious, life-long illness. It is characterized by a transmural, usually granulomatous, inflammation that leads to ulceration of the mucosa, intestinal stricture, and fistula formation. In many cases of pediatric Crohn's disease, the onset is insidious with nonspecific gastrointestinal (GI) symptoms or extraintestinal manifestations leading to delayed or incorrect diagnosis. The most common presenting symptoms of the disease include diarrhea, abdominal pain, fever, and weight loss. Symptoms associated with small bowel involvement or upper GI involvement include postprandial cramping, early satiety, nausea, anorexia, and diarrhea. As with adults, there is considerable variability in the clinical course of Crohn's disease in children. The general principles of treatment of pediatric Crohn's disease mirror those that are applicable to adults. However, the management of pediatric Crohn's disease presents greater and unique challenges because of the impact of the disease on their growth, development, quality of life, long-term disease-related complications, and potential sequelae of therapy in later life. The primary objective of this study is to characterize the safety and clinical effects of sargramostim treatment with and without concomitant corticosteroid induction therapy, after the first cycle and after repeated cycles if protocol requirements are met, in pediatric patients with active Crohn's disease. Secondary objectives are to: (1) Characterize the pharmacokinetic and pharmacodynamic properties of sargramostim treatment with and without concomitant corticosteroids in pediatric patients with Crohn's disease; and (2)Evaluate the efficacy of sargramostim treatment with and without concomitant corticosteroids, as measured by the Pediatric Crohn's Disease Activity Index (PCDAI; response defined as decrease greater than or equal to 12.5 points), Physician's Global Assessment (PGA), and IMPACT-III questionnaire (patients 10 years of age and older).