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An inhaled PDGF receptor inhibitor for the treatment of pulmonary arterial hypertension

吸入性PDGF受体抑制剂治疗肺动脉高压

基本信息

批准号：
9326326
负责人：
LAWRENCE S. ZISMAN
金额：
$ 99.98万
依托单位：
PULMOKINE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2018-11-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9326326
关键词：
Animals Award Blinded Breathing Canis familiaris Clinical Trials Contracts Cyclic GMP Disease Dose Drug Kinetics Formulation Funding Funding Agency Grant Guidelines Howard Temin Award Human Human Volunteers Lead Length Manufacturer Name Maximum Tolerated Dose Methods Morbidity - disease rate National Heart, Lung, and Blood Institute Patients Performance Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Phase III Clinical Trials Placebo Control Platelet-Derived Growth Factor Receptor Powder dose form Protocols documentation Public Health Rare Diseases Rattus Reporting Research Safety Scleroderma Secondary to Single-Blind Study Small Business Innovation Research Grant Time TimeLine Toxicology Vasodilator Agents clinical research site commercialization design effective therapy exposed human population healthy volunteer human study in vivo inhibitor/antagonist kinase inhibitor mortality novel performance site preclinical efficacy primary pulmonary hypertension public health relevance pulmonary arterial hypertension safety study

项目摘要

DESCRIPTION (provided by applicant): Pulmokine is developing a novel inhaled PDGF receptor (PDGFR) kinase inhibitor, PK10571 as a treatment for Pulmonary Arterial Hypertension (PAH). The purpose of this Phase IIB Small Market Bridge Award is to progress PK10571 through a phase 1A clinical trial for safety. PAH is an orphan disease with high morbidity and mortality despite currently available treatments. Pulmokine's current Phase II SBIR grant was designed to develop the formulation for inhalation of the API, determine pharmacokinetics, and maximum tolerated dose in the rat. These studies have been accomplished, and set the stage for IND enabling studies. The IND enabling studies will consist of in vivo animal toxicology studies in two species (rat and dog) as required by the FDA. These studies are currently funded separately through a Stage B VITA contract awarded to Pulmokine through the NHLBI. The phase IIB small market award will provide the means to perform a phase 1A first in human exposure clinical trial in healthy volunteers and to perform longer term toxicology studies. After completion of the Phase 1A clinical trial a combined phase 1B/2A clinical trial in patients with PAH will be performed with investor funds. The primary endpoint of the phase 1B/2A trial will be safety, with efficacy as a secondary endpoint. After completion of the phase 1B/2A trial, Pulmokine will form a strategic alliance or partnership with a larger pharmaceutical company (or undergo acquisition). Such an alliance will allow performance of a phase III clinical trial and commercialization of our drug product as a treatment for PAH. The part of the project that will be funded by this phase IIB award includes the following: 1) Performance of a phase 1A safety study of dry powder inhaled PK10571 in healthy human volunteers. This phase 1A clinical trial will consist of a blinded single ascending dose (SAD) placebo controlled protocol followed by a multiple dose ascending (MAD) placebo controlled protocol. All of the key components are in place to perform this first in human clinical trial: 1) cGMP manufacturer of of the API (IRIX Pharmaceuticals) ; 2) cGMP manufacture of spray dry powder formulation (BEND Research Inc.); 3) the Clinical site for Performance: (Parexel Phase 1 Unit). 2) Performance of a 6 month GLP toxicology study in the rat. This study is necessary per ICH M3(R2) guidelines before initiation of the longer phase 2 clinical trial. ICH guidelines recommend toxicology studies of the same length as the clinical trial for trials of 3-6 months duration. Since the Phase 1B/2A trial is planned for six months, we will need the 6 month rat GLP tox study.

描述（由申请人提供）：Pulmokine 正在开发一种新型吸入性 PDGF 受体 (PDGFR) 激酶抑制剂 PK10571，用于治疗肺动脉高压 (PAH)。该 IIB 期小市场桥梁奖的目的是推动 PK10571 通过 1A 期临床试验以确保安全。尽管目前有可用的治疗方法，PAH 仍是一种发病率和死亡率较高的孤儿疾病。 Pulmokine 目前的 II 期 SBIR 资助旨在开发吸入 API 的配方、确定药代动力学和大鼠的最大耐受剂量。这些研究已经完成，并为 IND 赋能研究奠定了基础。 IND 授权研究将包括 FDA 要求的两个物种（大鼠和狗）的体内动物毒理学研究。这些研究目前通过 NHLBI 授予 Pulmokine 的 B 阶段 VITA 合同单独资助。 IIB 期小市场奖励将提供在健康志愿者中首先进行 1A 期人体暴露临床试验以及进行长期毒理学研究的方法。 1A 期临床试验完成后，将利用投资者资金对 PAH 患者进行 1B/2A 期联合临床试验。 1B/2A 期试验的主要终点是安全性，疗效是次要终点。 1B/2A期试验完成后，Pulmokine将与一家更大的制药公司结成战略联盟或合作伙伴（或进行收购）。这样的联盟将允许进行 III 期临床试验并将我们的药物产品商业化作为 PAH 的治疗方法。该项目将由该 IIB 阶段资助的部分包括以下内容： 1) 在健康人类志愿者中进行干粉吸入 PK10571 的 1A 阶段安全性研究。该 1A 期临床试验将包括盲法单剂量递增 (SAD) 安慰剂对照方案，随后是多剂量递增 (MAD) 安慰剂对照方案。所有关键组件均已到位，可在人体临床试验中首次执行此操作：1) API 的 cGMP 制造商（IRIX Pharmaceuticals）； 2) 喷雾干粉制剂的 cGMP 制造（BEND Research Inc.）； 3) 临床表现站点：（Parexel Phase 1 Unit）。 2) 在大鼠中进行 6 个月的 GLP 毒理学研究。根据 ICH M3(R2) 指南，在开始更长的 2 期临床试验之前，这项研究是必要的。 ICH 指南推荐毒理学研究持续时间为 3-6 个月的试验与临床试验的长度相同。由于 1B/2A 期试验正在进行计划为期六个月，我们将需要为期 6 个月的大鼠 GLP 毒性研究。