Moving a new anti-tubercular drug candidate SQ109 into clinical trials

描述（由申请人提供）：本申请的总体目标是及时推进新型抗结核候选药物SQ109进入人类志愿者I期临床试验。由Sequella与NIH合作开发的SQ109是一种小分子候选药物，正在开发用于治疗肺结核（TB）。它具有口服生物利用度，对结核分枝杆菌具有高效力，对高度耐药的M。结核病，并适用于取代一线药物乙胺丁醇在密集阶段的世卫组织推荐的直接观察治疗（DOT）药物方案。目前，SQ109已完成临床前开发，我们预计将在短期内提交IND。已经开发了初步的1a期和1b期临床方案，以确定安全性和耐受性，并评估单剂量（1a期）和多剂量（1b期）给药后SQ109在健康男性和女性志愿者中的药代动力学。目前的R34资助申请将使我们能够完成试验的规划和设计，并准备新药临床试验质量管理规范（GCP）试验所需的文件。具体而言，在计划期间，我们将分析1a期和1b期临床研究的初步设计，并与我们的NIH同事一起进行必要的修改。我们将在方案中纳入动物研究数据，以确定健康成人受试者的初始剂量，并解决潜在的毒性问题。我们还将为临床试验选择CRO并获得IRB对临床方案的批准，为研究选择CRO并获得相关机构审查委员会（IRB）的批准。我们将利用这一计划期，根据FDA法规为新的治疗药物SQ109制定研究者手册，并寻求确定的CRO的IRB批准。我们将制定知情同意书，代表人类志愿者对计划研究的同意。知情同意书也将在试验开始前获得批准。

DESCRIPTION (provided by applicant): The overall goal of this application is the timely advancement of a new anti-tuberculosis drug candidate, SQ109, into Phase I Clinical Trials in human volunteers. Developed by Sequella in partnership with the NIH, SQ109 is a small molecule drug candidate that is being developed for the treatment of pulmonary tuberculosis (TB). It is orally bioavailable, has high potency against Mycobacterium tuberculosis, is effective against profoundly drug-resistant M. tuberculosis, and is suitable to replace the first-line drug ethambutol during the intensive phase of the WHO-recommended Directly Observed Therapy (DOT) drug regimen. At the present time, SQ109 has completed preclinical development, and we expect to file an IND shortly. Preliminary Phase 1a and Phase 1b clinical protocols have been developed to determine the safety and tolerability, and to evaluate the pharmacokinetics of SQ109 in healthy, male and female volunteers after a single-dose (Phase la) and a multiple-dose (Phase Ib) administration. The present R34 Grant Application will allow us to complete the planning and design of the trials, and to prepare the necessary documentation that accompanies Good Clinical Practice (GCP) trials of new drugs. Specifically, during the planning period we will analyze the preliminary design of both Phase 1a and 1b clinical studies and make necessary changes with our NIH colleagues. We will incorporate the animal studies data into the protocols to establish the initial dose for healthy adult subjects and to address potential toxicity issues. We will also select CRO for the clinical trials and obtain approval of the clinical protocols from the IRB, select a CRO for the studies, and obtain approval from the relevant Institutional Review Board, IRB. We will use this planning period to develop the Investigator's Brochure for new therapeutic SQ109 based on FDA regulations, and seek approval from the IRB of identified CRO. We will develop the Informed Consent that represents an agreement of human volunteers to the planned studies. The informed consent will also be approved before the trials begin.