HBI-002 to Treat Diabetic Retinopathy

HBI-002 治疗糖尿病视网膜病变

基本信息

批准号：
10323484
负责人：
Edward Gomperts
金额：
$ 29.99万
依托单位：
HILLHURST BIOPHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323484
关键词：
Acute Address Adult Affect Age Animal Model Animals Antioxidants Apoptosis Basic Science Bilirubin Biliverdine Biochemical Biological Assay Biological Availability Blindness Blood Vessels Carbon Monoxide Characteristics Clinical Clinical Research Clinical Trials Complications of Diabetes Mellitus Contralateral Coupled Data Data Set Development Diabetes Mellitus Diabetic Retinopathy Diabetic mouse Disease Dose Drug Kinetics Elderly Evaluation Exhibits Eye Fibrosis Formulation Gases Gastrointestinal tract structure Gene Expression Genes Health Heme Histologic Human Hyperglycemia Inflammation Inflammatory Inhalation Injury Iron Ischemia Left Light Coagulation Literature Methods Modality Modeling Monitor Morphology Mus Nerve Degeneration Neuronal Injury Neurons Ophthalmology Oral Oxidative Stress Pathology Patients Pharmaceutical Preparations Pharmacologic Substance Phase Phenotype Pre-Clinical Model Property Reactive Oxygen Species Regimen Reperfusion Injury Reperfusion Therapy Research Research Personnel Research Support Retina Retinal Degeneration Retinal Diseases Risk Safety Streptozocin Structure Technology Testing Therapeutic Therapeutic Intervention Time Toxic effect Toxicology Treatment Efficacy Vision Visual impairment Work base bevacizumab clinically relevant diabetic direct application drug development efficacy study glycemic control heme oxygenase-1 human model improved outcome in vivo infection risk innovation mouse model neurovascular neurovascular injury novel novel therapeutics pharmacokinetics and pharmacodynamics phase 1 testing pre-clinical preclinical study prevent protective effect retinal ischemia success

Acute Address Adult Affect Age Animal Model Animals Antioxidants Apoptosis Basic Science Bilirubin Biliverdine Biochemical Biological Assay Biological Availability Blindness Blood Vessels Carbon Monoxide Characteristics Clinical Clinical Research Clinical Trials Complications of Diabetes Mellitus Contralateral Coupled Data Data Set Development Diabetes Mellitus Diabetic Retinopathy Diabetic mouse Disease Dose Drug Kinetics Elderly Evaluation Exhibits Eye Fibrosis Formulation Gases Gastrointestinal tract structure Gene Expression Genes Health Heme Histologic Human Hyperglycemia Inflammation Inflammatory Inhalation Injury Iron Ischemia Left Light Coagulation Literature Methods Modality Modeling Monitor Morphology Mus Nerve Degeneration Neuronal Injury Neurons Ophthalmology Oral Oxidative Stress Pathology Patients Pharmaceutical Preparations Pharmacologic Substance Phase Phenotype Pre-Clinical Model Property Reactive Oxygen Species Regimen Reperfusion Injury Reperfusion Therapy Research Research Personnel Research Support Retina Retinal Degeneration Retinal Diseases Risk Safety Streptozocin Structure Technology Testing Therapeutic Therapeutic Intervention Time Toxic effect Toxicology Treatment Efficacy Vision Visual impairment Work base bevacizumab clinically relevant diabetic direct application drug development efficacy study glycemic control heme oxygenase-1 human model improved outcome in vivo infection risk innovation mouse model neurovascular neurovascular injury novel novel therapeutics pharmacokinetics and pharmacodynamics phase 1 testing pre-clinical preclinical study prevent protective effect retinal ischemia success

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项目摘要

PROJECT SUMMARY Diabetic retinopathy (DR) is a neurovascular complication of diabetes mellitus and the leading cause of blindness in working age adults and elderly, affecting approximately 4.2 million diabetes patients in the US, of which 655,000 have vision-threatening DR. There is an urgent need for the development of additional approaches to prevent and treat diabetic retinopathy, as the current therapeutic interventions have limited efficacy and substantial drawbacks. In multiple preclinical studies, we and others have demonstrated the cytoprotective properties of low dose carbon monoxide (CO) in various disease states, including in ischemia- associated diseases such as DR To date, inhaled CO gas (iCO) and CO bound to carrier molecules (CORMs) have been the modalities of choice in the majority of animal and in all the clinical studies carried out to study the potential benefit of low dose CO. However, iCO and CORMS are not expected to be pharmaceutically acceptable and viable therapeutic options due to, with iCO, the risk of inadvertent exposure from the presence of compressed CO cylinders as well as difficulties in controlling dosing and, with CORMs, carrier molecule toxicology, stability, and CO release characteristics that have proven to be a substantial barrier to development. The objective of the proposed project is to investigate HBI-002, a novel oral CO drug product, to prevent and treat DR. The safety and tolerability of CO has been demonstrated in 25 successful Phase 1 and 2 clinical studies by others in other indications supported by well-defined preclinical data sets that led to approval by the FDA for human testing. HBI-002 comprises an oral formulation containing precise amounts of CO that are not bound to a carrier molecule (i.e. not a CORM). Preclinical in vivo pharmacokinetic studies demonstrated proof-of- concept feasibility, tolerability, and bioavailability. The next step in development is to demonstrate that HBI-002 is effective in clinically relevant animal models of DR and to better understand the potential mechanism(s) of action. Based upon the substantial literature of CO in protecting against ischemia-associated and ophthalmologic disease, our central hypothesis that will be tested in this project is: HBI-002 will prevent DR by reducing oxidative stress and inflammation.

项目摘要糖尿病性视网膜病（DR）是糖尿病的神经血管并发症，是主要原因成人和老年人的失明，影响美国约420万糖尿病患者有655,000的危害视力的DR。迫切需要开发额外预防和治疗糖尿病性视网膜病的方法，因为当前的治疗干预措施有限功效和实质性缺点。在多项临床前研究中，我们和其他人证明了低剂量一氧化碳（CO）在各种疾病状态中的细胞保护特性，包括缺血 - 相关疾病，例如DR 迄今大多数动物和所有临床研究的选择然而，剂量co。由于ICO，压缩CO的存在无意中暴露的风险是由于治疗选择圆柱体以及控制剂量的困难以及载体分子毒理学，稳定性和 CO释放特征已被证明是发展的实质性障碍。目的拟议的项目是研究一种新型的口服CO药物HBI-002，以预防和治疗DR。在25阶段1和2的临床研究中，CO的安全性和耐受性已通过其他指示的其他指示支持明确指示的临床前数据集，导致FDA批准人类测试。 HBI-002包括一个口服配方载体分子（即不是Corm）。临床前体内药代动力学研究证明了证明概念可行性，耐受性和生物利用度。开发的下一步是证明HBI-002 在DR的临床相关动物模型中有效，以更好地了解行动。基于CO的大量文献，以防止缺血相关和眼科疾病，我们将在该项目中测试的中心假设是：HBI-002将防止DR 通过减少氧化应激和炎症。