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

描述(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，而且容易损害伤口愈合。发病率和住院的一个主要原因是糖尿病足溃疡(DFU)，它可能导致感染、坏疽、需要长期住院的截肢、昂贵的治疗，并可能严重损害患者的生活质量。DFU每年给美国医疗体系带来的成本超过100亿美元。糖尿病创面往往在创面愈合的最初炎症阶段停滞不前，通常对常规治疗没有反应。目前的治疗方法包括清创、压力卸载、感染控制、负压和皮肤替代物，往往疗效不佳，成本较高。存在着对更容易和更有效的治疗的大量未得到满足的需求。FirstStringResearch，Inc.是一家临床阶段的生物技术公司，该公司正在推进基于连接蛋白C末端的新型生物工程多肽的开发，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。一种基于连接蛋白43(Cx43)的先导肽CT1(25个氨基酸)显示出独特的能力，可以将人体自身的愈合反应从炎症和疤痕转换到健康的再生阶段。FSR在第一阶段和第二阶段SBIR/STTR拨款的帮助下，开发了一种名为Granexin(Tm)Gel的局部产品的ACT1；获得了IND批准；并在一次第一阶段(N=48)和两(2)阶段II(N=92)临床试验中证明了其MOA、安全性和有效性。Granexin(Tm)Gel已被证明是安全有效的，没有免疫原性的证据。FSR建议进行2b期人体(N=180)临床试验，以评估Granexin(Tm)Gel治疗DFU的安全性和有效性。这项试验将涉及3组患者：Granexin(Tm)Gel(100M？CT1)+标准护理(SOC)；Granexin(Tm)Gel(200M？CT1)+SOC；或Vehicle Gel+SOC。由于CT1的S独特的MOA，我们假设与赋形剂+SOC相比，格兰欣(TM)凝胶将显著加速DFU患者的伤口闭合。这一假设将通过以下具体目标进行验证：评估局部应用Granexin(Tm)Gel治疗糖尿病足部溃疡的安全性和有效性。主要终点是从基线到12周的伤口闭合率为100%。次要终点包括4周的平均伤口闭合率，受试者对疼痛强度的自我评估(至第12周)，50%和100%的伤口闭合时间。安全性变量将是与治疗相关的不良事件的发生率。该项目取得的进一步临床成功将使Granexin(Tm)Gel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，从而为治疗DFU患者的新疗法奠定基础。

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.