Angiotensin Analogs to Treat Wound Healing

血管紧张素类似物治疗伤口愈合

• 批准号: 7414073
• 负责人: KATHLEEN E. RODGERS
• 金额: $ 85.92万
• 依托单位: US BIOTEST, INC.
• 依托单位国家: 美国
• 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/7414073
• 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

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、压力和静脉淤滞性溃疡相关的慢性伤口。在许多情况下，慢性伤口可能需要数年才能愈合，复发率很高，每年将导致54，000名患者截肢。据估计，美国有220万患者患有对传统疗法无反应的慢性溃疡。在US Biotest，Inc.进行的临床前研究中，血管紧张素肽已被证明可有效促进伤口愈合。与南加州大学凯克医学院的科学家合作。在II期SBIR资助中，US Biotest开发了USB 001（NorLeu 3-A（1-7），含2% HEC和防腐剂），这是一种适合临床研究的血管紧张素肽制剂。USB 001被发现是稳定的，局部使用安全，并且在促进糖尿病小鼠伤口愈合方面比Regranex更有效。在与FDA的IND前会议期间，当US Biotest的临床开发计划被批准用于IND申请时，对这些数据进行了审查。此外，US Biotest确定了NorLeu 3-A（1-7）在伤口愈合中的治疗反应基因和两种潜在的分子作用机制。在我们的第二阶段SBIR赠款和IND（于2006年7月11日获得FDA批准）建立的基础上，US Biotest正在提交一项竞争性继续申请，以启动临床试验，评估USB 001的安全性和有效性，以建立概念证明。在具体目标1中，我们将在正常志愿者（N=9）中进行I期安全性研究，并在我们的LC/MS/MS分析中测量NorLeu 3-A（1- 7）的毒代动力学和药代动力学样本。在具体目标2中，我们将生产无菌USB 001，并在慢性溃疡糖尿病患者中进行II期剂量反应研究（3组，每组25名研究受试者）。在具体目标3中，我们将完成启动III期临床研究所需的临床前安全性研究。血管紧张素类似物治疗伤口愈合糖尿病是一种困扰美国估计2000万人的疾病（National Diabetes Information Clearinghouse，2005）。糖尿病的并发症包括慢性皮肤溃疡，由于持续的伤口感染，慢性皮肤溃疡经常导致截肢和生命损失。US Biotest的先导化合物NorLeu 3-A（1-7）在临床前研究中已被证明比Regranex更有效，Regranex是FDA批准的唯一治疗糖尿病溃疡的药物。我们的第二阶段SBIR的这一竞争性延续将使US Biotest能够进行临床疗效的第一阶段和第二阶段研究。开发成功的糖尿病溃疡治疗方法将保持和改善生活质量，并降低医疗保健成本。