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，而且伤口愈合容易受损。发病和住院的一个主要原因是糖尿病足溃疡（DFUs），它可能导致感染、坏疽、截肢，需要长期住院治疗和昂贵的治疗，并可能严重损害患者的生活质量。DFU每年给美国医疗系统带来的成本超过100亿美元。糖尿病创面往往停留在创面愈合的初始炎症阶段，通常对常规治疗无反应。目前的治疗方法包括清创、卸压、感染控制、负压、皮肤代用品等，往往疗效甚微且费用高。对一种更容易和更有效的治疗方法的巨大需求尚未得到满足。FirstString Research, Inc. （FSR）是一家临床阶段的生物技术公司，正在推进基于连接蛋白c端的新型生物工程肽的开发；一种在伤口愈合过程的多个方面起重要作用的蛋白质。一种基于连接蛋白43 （Cx43）的先导肽¿CT1（25个氨基酸）已经显示出一种独特的能力，可以将身体自身的愈合反应从炎症和疤痕转变为健康的再生阶段。FSR在I期和II期SBIR/STTR资助的帮助下，开发了一种名为Granexin（tm）凝胶的外用产品ACT1；获得IND批准；并在一项I期（N=48）和两项II期（每个试验N=92）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有效的，没有免疫原性的证据。FSR建议开展2b期人体（N=180）临床试验，以评估Granexin（tm）凝胶治疗DFUs的安全性和有效性。该试验将涉及3组患者接受：Granexin（tm）凝胶（100¿M¿CT1） +标准护理（SOC）；Granexin(tm) Gel(200¿M¿CT1) + SOC；或车辆凝胶+ SOC。由于¿CT1独特的MOA，我们假设与Vehicle + SOC相比，Granexin（tm）凝胶将显著加速DFU患者的伤口愈合。该假设将通过以下具体目的进行检验：评估局部给药Granexin（tm）凝胶治疗糖尿病足溃疡的安全性和有效性。主要终点将是基线至第12周100%伤口愈合的发生率。次要终点将包括4周时伤口愈合的平均百分比，受试者自我评估疼痛强度（直到第12周），伤口愈合50%和100%的时间。安全性变量将是治疗相关不良事件的发生率。该项目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，并随后进行产品商业化，从而为DFUs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.