Evaluation Of A Novel Connexin-Based Peptide For The Treatment Of Diabetic Wounds

描述（由申请人提供）：根据ADA，2580万儿童和成人患有糖尿病。糖尿病患者患心脏病等并发症的风险增加，并且易于受损的伤口愈合。发病率和住院治疗的主要原因是糖尿病足溃疡（DFU），其可导致感染、坏疽、需要延长住院时间的截肢、昂贵的治疗，并且可显著损害患者的生活质量。DFU对美国医疗保健系统的成本每年超过100亿美元。糖尿病伤口倾向于在伤口愈合的初始炎症阶段保持停滞，并且通常对常规治疗无反应。目前的治疗方法，包括清创术，压力卸载，感染控制，负压和皮肤替代品往往具有边际疗效和高成本。对于更容易和更有效的治疗存在大量未满足的需求。FirstString Research，Inc. (FSR)一家临床阶段的生物技术公司，正在推进基于连接蛋白C末端的新型生物工程肽的开发;连接蛋白是一种在伤口愈合过程的多个方面具有重要作用的蛋白质。一种先导肽？基于连接蛋白43（Cx43）的CT 1（25个氨基酸）已经证明了将身体自身的愈合反应从炎症和瘢痕形成切换到健康再生阶段的独特能力。FSR在I期和II期SBIR/STTR赠款的帮助下，开发了一种名为Granexin（TM）凝胶的局部产品中的ACT 1;获得了IND批准;并在I期（N=48）和两（2）期II（N=92每次试验）临床试验中证明了其MOA，安全性和有效性。Granexin（TM）凝胶已被证明是安全和有效的，没有免疫原性的证据。FSR建议进行2b期人体（N=180）临床试验，以评价Granexin（TM）凝胶治疗DFU的安全性和有效性。本试验将涉及3组接受：Granexin（TM）凝胶（100 <$M <$CT 1）+标准治疗（SOC）; Granexin（tm）凝胶（200 <$M <$CT 1）+ SOC;或溶剂凝胶+SOC。CT 1独特的MOA，我们假设Granexin（TM）凝胶将显著加速DFU患者的伤口闭合，将通过以下具体目的来检验该假设：评价局部给予糖尿病足溃疡的GranexinTM凝胶的安全性和有效性。主要终点为从基线至第12周100%伤口闭合的发生率。次要终点将包括4周时的平均伤口闭合百分比、受试者疼痛强度的自我评估（直至第12周）、至50%和100%伤口闭合的时间。安全性变量为治疗相关不良事件的发生率。该项目取得的进一步临床成功将使Granexin凝胶进入关键的3期试验，获得FDA的批准，并随后实现产品商业化，从而为DFU患者的新型治疗奠定基础。

DESCRIPTION (provided by applicant): According to the ADA, 25.8 million children and adults have diabetes. Diabetics have an increased risk of complications such as heart disease and are prone to impaired wound healing. A major cause of morbidity and hospitalization is diabetic foot ulceration (DFUs) that may result in infection, gangrene, amputations requiring prolonged hospitalization, costly treatments, and can significantly impair a patient's quality of life. The cost of DFU's to the US healthcare system is over $10 Billion annually. Diabetic wounds tend to remain stalled in the initial inflammatory phase of wound healing and are generally unresponsive to conventional treatments. Current treatment approaches including debridement, pressure off-loading, infection control, negative pressure, and skin substitutes tend to have marginal efficacy and high cost. A large unmet need exists for an easier and more effective treatment. FirstString Research, Inc. (FSR), a clinical stage biotech company, is advancing the development of novel bioengineered peptides based on the c-terminus of connexin proteins; a protein with important roles in multiple aspects of the wound healing process. A lead peptide ¿CT1 (25 amino acids) based on connexin 43 (Cx43) has demonstrated a unique capability of switching the body's own healing response from inflammation and scarring to a healthy regenerative stage. FSR, with the assistance of Phase I and II SBIR/STTR grants, has developed ACT1 in a topical product called Granexin(tm) Gel; obtained IND approval; and demonstrated its MOA, safety, and efficacy in a Phase I (N=48) and two (2) Phase II (N=92 per trial) clinical trials. Granexin(tm) Gel has been shown to be safe and efficacious with no evidence of immunogenicity. FSR proposes to conduct a Phase 2b human (N=180) clinical trial to evaluate safe and efficacy of Granexin(tm) Gel for treating DFUs. This trial will involve 3 grous to receive: Granexin(tm) Gel (100 ¿M ¿CT1) + Standard of Care (SOC); Granexin(tm) Gel (200 ¿M ¿CT1) + SOC; or Vehicle Gel + SOC. Due to ¿CT1's unique MOA, we hypothesize that Granexin(tm) Gel will significantly accelerate wound closure in DFU patients, when compared to Vehicle + SOC. The hypothesis will be tested through the following specific aims: To evaluate the safety and efficacy of Granexin(tm) Gel administered topically to Diabetic Foot Ulcer. The primary endpoint will be the incidence of 100% wound closure from Baseline to Week 12. The secondary endpoints will include mean percent wound closure at 4 weeks, subject self-assessment of intensity of pain (till Week 12), time to 50% and 100% wound closure. The safety variable will be the incidence of treatment related Adverse Events. Further clinical success achieved with this project will enable the advancement Granexin(tm) Gel toward pivotal Phase 3 trials, obtaining FDA's approval, and subsequent product commercialization, thus laying the foundation for a novel therapeutic for patients suffering from DFUs.