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将一种新的抗结核候选药物SQ109推进到人类志愿者的第一阶段临床试验中。由Sequella与美国国立卫生研究院合作开发的SQ109是一种正在开发的治疗肺结核(TB)的小分子候选药物。它具有口服生物利用度，对结核分枝杆菌具有高效力，对高度耐药的结核分枝杆菌有效，适合在世卫组织推荐的直接观察疗法(DOT)药物方案的强化阶段替代一线药物乙胺丁醇。目前，SQ109已经完成了临床前开发，我们预计很快就会提交IND。已经制定了初步的1a期和1b期临床方案，以确定SQ109的安全性和耐受性，并评估SQ109在单剂(1a期)和多剂(Ib期)给药后在健康、男性和女性志愿者中的药代动力学。目前的R34拨款申请将使我们能够完成试验的规划和设计，并准备伴随良好临床实践(GCP)新药试验的必要文件。具体地说，在规划期间，我们将分析1a期和1b期临床研究的初步设计，并与NIH的同事一起进行必要的修改。我们将把动物研究数据纳入方案，以确定健康成年受试者的初始剂量，并解决潜在的毒性问题。我们还将选择CRO进行临床试验，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的批准。我们将利用这一规划期根据FDA的规定制定新的治疗SQ109的研究人员手册，并寻求已确定的CRO的IRB的批准。我们将制定知情同意，代表人类志愿者对计划中的研究的同意。知情同意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.