Angiotensin Analogs to Treat Wound Healing

血管紧张素类似物治疗伤口愈合

基本信息

批准号：
7270998
负责人：
KATHLEEN E. RODGERS
金额：
$ 92.41万
依托单位：
US BIOTEST, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270998
关键词：
Acceleration Agreement American Amputation Angiotensin II Angiotensins Area Award Becaplermin Biological Assay Blood Blood Pressure Burn injury Chronic Cicatrix Clinic Clinical Clinical Chemistry Clinical Investigator Clinical Research Clinical Trials Closure Collaborations Complications of Diabetes Mellitus Condition Coupled Daily Data Decubitus ulcer Dental Dermatology Development Development Plans Diabetes Mellitus Diabetic mouse Diabetic ulcer Dose Double-Blind Method Drug Formulations Drug Kinetics Drug Packaging Effectiveness Electrocardiogram Epithelial Evaluation Forearm Foundations Funding Genes Genetic Goals Grant Healed Health Health Care Costs Hematology Hour Human In Vitro Individual Investigational Drugs Investigational New Drug Application Laboratories Lead Life Liquid Chromatography Mass Spectrum Analysis Measures Methods Molecular Molecular Mechanisms of Action Neuraxis Occlusive Dressings Oryctolagus cuniculus Patients Peptides Pharmaceutical Preparations Pharmacology Phase Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical Trials Placebos Plague Preparation Production Quality of life Randomized Rate Rattus Recurrence Safety Sampling Scientist Series Site Skin Skin Ulcer Small Business Funding Mechanisms Small Business Innovation Research Grant Specific qualifier value Stasis Ulcer Sterile coverings Sterility Study Subject Technology Teratology Testing Time Toxicokinetics Toxicology Ulcer United States United States Food and Drug Administration United States National Institutes of Health Venous Venous Pressure level Week Wound Healing Wound Infection Writing analog clinical efficacy concept day diabetic drug development foot genotoxicity healing improved in vivo medical schools norLeu3-A(1-7)pre-clinical preclinical study repaired respiratory response size volunteer

项目摘要

DESCRIPTION (provided by applicant): Americans suffer from chronic wounds associated with diabetic, pressure and venous stasis ulcers. In many cases, chronic wounds can take years to heal, have a high recurrence rate and will result in amputations for 54,000 patients annually. It is estimated that 2.2 million patients in the United States have chronic ulcers that don't respond to conventional therapies. Angiotensin peptides have been shown to effectively promote wound healing in preclinical studies undertaken at US Biotest, Inc. in collaboration with scientists at USC KECK School of Medicine. In a Phase II SBIR grant, US Biotest developed USB001 (NorLeu3-A(1-7) in 2% HEC and preservatives), an angiotensin peptide formulation appropriate for clinical study. USB001 was found to be stable, safe for topical use and more effective than Regranex in facilitating wound healing in diabetic mice. Much of this data was reviewed during a pre-IND meeting with the FDA when US Biotest's clinical development plan was approved for IND filing. In addition, US Biotest identified treatment responsive genes and two potential molecular mechanisms of action for NorLeu3-A(1-7) in wound healing. Building upon the foundation established in our Phase II SBIR grant and our IND (approved by FDA on July 11, 2006), US Biotest is submitting a competing continuation to initiate clinical trials for evaluation of USB001's safety and efficacy sufficient to establish proof of concept. In Specific Aim 1, we will conduct a Phase I safety study in normal volunteers (N=9) and measure toxicokinetic and pharmacokinetic samples in our LC/MS/MS assay for NorLeu3-A(1- 7). In Specific Aim 2, we will manufacture sterile USB001 and conduct a Phase II dose response study in diabetic patients with chronic ulcers (3 groups of 25 study subjects per group). In Specific Aim 3, we will complete preclinical safety studies required to initiate Phase III clinical studies. Angiotensin Analogs to Treat Wound Healing Diabetes is an illness that plagues an estimated 20 million individuals in the United States (National Diabetes Information Clearinghouse, 2005). Complications of diabetes include chronic skin ulcers that often lead to amputation and loss of life due to persistent wound infection. US Biotest's lead compound, NorLeu3-A(1-7), has been shown in pre-clinical studies to be significantly more effective than Regranex, the only FDA-approved drug for healing diabetic ulcers. This competing continuation of our Phase II SBIR will allow US Biotest to conduct Phase I and II studies of clinical efficacy. Development of a successful treatment for diabetic ulcers will preserve and improve quality of life as well as reduce health care costs.

描述（由申请人提供）：美国人患有与糖尿病，压力和静脉暂停溃疡有关的慢性伤口。在许多情况下，慢性伤口可能需要数年的时间才能愈合，复发率很高，并且每年将为54,000名患者截肢。据估计，美国有220万例患者患有慢性溃疡对常规疗法没有反应。在美国Biotest，Inc。与USC Keck医学院的科学家合作的临床前研究中，血管紧张素肽可有效促进伤口愈合。在II期SBIR拨款中，美国Biotest开发了USB001（Norleu3-A（1-7），在2％HEC和防腐剂中），这是一种适合临床研究的血管紧张素肽配方。发现USB001稳定，可用于局部使用，并且比Regranex在促进糖尿病小鼠的伤口愈合方面更有效。当美国Biotest的临床开发计划被批准用于IND提交时，在与FDA的一次预先会议上进行了审查。此外，美国Biotest在伤口愈合中确定了治疗的反应基因和Norleu3-A（1-7）的两种潜在的分子机制。在我们II阶段SBIR赠款和IND（2006年7月11日FDA批准）中建立的基金会的基础上，美国Biotest提交了竞争性延续，以启动临床试验，以评估USB001的安全性和功效，足以建立概念证明。在特定的目标1中，我们将对正常志愿者（n = 9）进行I期安全研究，并在我们的LC/MS/MS/MS分析中测量Norleu3-A（1-7）的LC/MS/MS分析中的有毒动力学和药代动力学样品。在特定的目标2中，我们将对患有慢性溃疡的糖尿病患者（每组25名研究对象）进行II期剂量反应研究。在特定目标3中，我们将完成启动III期临床研究所需的临床前安全研究。血管紧张素类似物治疗伤口愈合糖尿病是一种困扰着美国估计有2000万人的疾病（国家糖尿病信息清算室，2005年）。糖尿病并发症包括慢性皮肤溃疡，这些溃疡通常导致截肢和由于持续的伤口感染而导致的生命丧失。在临床前研究中，美国Biotest的铅化合物Norleu3-A（1-7）比Regranex明显更有效，Regranex是唯一用于治愈糖尿病性溃疡的FDA批准药物。我们II期SBIR的这种竞争延续将使我们能够对临床功效进行I和II期研究。开发成功的糖尿病性溃疡治疗方法将保留和改善生活质量并降低医疗保健成本。