A Phase 2, randomized, double-blind, 4-arm, multicenter study to demonstrate the efficacy and safety of topical dosage formulations of a prescription drug product for actinic keratosis

一项 2 期、随机、双盲、4 组、多中心研究，旨在证明处方药局部剂量制剂治疗光化性角化病的有效性和安全性

• 批准号: 10820810
• 负责人: Steven Isaacman
• 金额: $ 100万
• 依托单位: NANOMETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10820810
• 关键词: Academy; Actinic keratosis; Address; Aftercare; American; Area; Biological Sciences; CD4 Positive T Lymphocytes; Calcipotriene; Cessation of life; Clinical; Clinical Research; Clinical Trials; Cold Therapy; Cream; Curettage procedure; Data; Dermatologist; Dermatology; Development; Diagnosis; Diffuse; Dose; Double-Blind Method; Drug Prescriptions; Effectiveness; Effector Cell; Exhibits; Face; Fluorouracil; Formulation; Goals; Health Insurance; Healthcare Systems; Immune response; Immune system; Immunity; Immunocompetent; Incentives; Individual; Insurance; Insurance Carriers; Keratosis; Knowledge; Legal patent; Lesion; Malignant Neoplasms; Market Research; Marketing; Metabolic Clearance Rate; Mission; Morbidity - disease rate; Multicenter Studies; National Cancer Institute; National Comprehensive Cancer Network; Neck; Outcome; Patients; Pharmaceutical Preparations; Pharmacy facility; Phase; Phase II Clinical Trials; Physicians; Placebo Control; Placebos; Price; Probability; Public Health; Publishing; Randomized; Reaction; Recommendation; Regimen; Regulation; Reporting; Research; Research Design; Risk; Risk Reduction; Safety; Sales; Scalp structure; Skin; Skin Carcinoma; Small Business Innovation Research Grant; Technology; Treatment Cost; UV induced; United States; United States Food and Drug Administration; adaptive immune response; arm; beneficiary; cancer type; commercial application; cost; design; dosage; efficacy evaluation; improved; interest; melanoma; mortality; open label; phase 3 study; premalignant; prevent; price lists; primary endpoint; randomized trial; recruit; secondary endpoint; side effect; skin lesion; skin squamous cell carcinoma; technological innovation; treatment duration; willingness

PROJECT SUMMARY / ABSTRACT Acinic Keratoses (AK) are premalignant skin lesions with the potential to develop into Cutaneous Squamous cell Carcinoma (CSCC), which is the second most common type of cancer and when metastatic has a mortality rate that is higher than melanoma. There is a high unmet need for topical AK medications with shorter treatment durations and enhanced efficacy that can eradicate AK and treat the surrounding cancerized field. The Product of this SBIR will be a Food and Drug Administration approved fixed dose combination cream containing calcipotriol (CPO) and 5-fluorouracil (5-FU) as a treatment for AK in immunocompetent patients. Technological Innovation: Topical co-administration of CPO / 5-FU eradicates AKs by activating CD4+ T cell dominated immunity, an upstream activator of the adaptive immune response, which then recruits an array of downstream effector cells to block CSCC development. The Long-Term Goal is the registration of the SBIR product, which directly addresses the mission of the National Cancer Institute by harnessing the power of the immune system to treat AKs and prevent CSCC. Phase I SBIR Equivalent Studies demonstrated the clinical and commercial feasibility of the PHD technology for AK treatment. Successfully completed randomized (n=130) and open label clinical studies (n=18) demonstrated the feasibility of the CPO / 5-FU combination as the best-in-class treatment for AK and the only product ever reported to reduce the risk of CSCC development at 3-years post treatment. The high impact of the published data has resulted in the National Comprehensive Cancer Network and the American Academy of Dermatology recommending CPO / 5-FU as a treatment for AK. Market research demonstrated prescriber and patient enthusiasm for the PHD product and confirmed that health insurance companies will provide broad coverage to beneficiaries at a price that will generate meaningful revenues for the company. Specific Aim 1. Complete a Phase 2, Randomized, Double-blind, 4-Arm, Multicenter Study to Demonstrate the Efficacy and Safety of Topical Dosage Formulations of CPO plus 5-FU for the treatment of AK. Phase II Objectives: Conduct a Phase 2 clinical trial to assess the efficacy and safety of topical dosage formulations containing two different concentrations of CPO plus 5-FU in 160 AK patients. Expected Outcomes: 5-FU / CPO is expected to be well-tolerated and significantly more efficacious than 5-FU monotherapy and placebo. The data will enable dose selection and design of the Phase 3 registrational studies. Commercial Opportunity: The target customer will be dermatologists and peak revenues of $285 mil are projected at the lowest probable list price, with 93% of patients paying ≤ $25 out-of-pocket.

项目摘要 /摘要 引起神经性kerations（AK）是抗皮肤损伤，有可能发展为皮肤方形细胞 癌（CSCC），这是第二种最常见的癌症类型，何时转移率具有死亡率 高于黑色素瘤。使用较短治疗的局部AK药物非常未满足 持续时间和提高效率，可以放射AK并处理周围取消的场。 该SBIR的产物将是食品药品管理局批准的固定剂量组合霜 含有钙蛋白酶（CPO）和5-氟尿嘧啶（5-FU）作为免疫能力患者的AK治疗。 技术创新：CPO / 5-FU radiotications AK的局部共同给药，通过激活CD4+ T细胞 自适应免疫响应的上游激活因子主导的免疫学，然后招募了一系列 下游效应细胞阻断CSCC的发展。 长期目标是SBIR产品的注册，该产品直接解决了国家的使命 癌症研究所通过利用免疫系统的力量来治疗AK并预防CSCC。 第一阶段SBIR等效研究证明了博士技术的临床和商业可行性 用于AK治疗。成功完成随机（n = 130）和开放标签临床研究（n = 18） 证明了CPO / 5-FU组合作为AK的同类课程的可行性，唯一 据报道，产品曾在治疗后3年降低CSCC开发的风险。高度影响 已发布的数据导致国家综合癌症网络和美国学院 皮肤病学建议CPO / 5-FU作为AK的治疗方法。市场研究证明了处方者和 患者对博士产品的热情，并确认健康保险公司将提供广泛的 对受益人的承保范围将为公司带来有意义的揭示。 特定目标1。完成2阶段2，随机，双盲，4臂，多中心研究，以证明 CPO和5-FU的局部剂量配方的功效和安全性用于治疗AK。 II期目标：进行2期临床试验以评估局部剂量的效率和安全性 在160名AK患者中包含两个不同浓度的CPO加5-FU的公式。 预期的结果：5-FU / CPO预计将具有良好的耐受性，并且效率明显比5-FU高得多 单一疗法和安慰剂。数据将使3阶段注册研究的剂量选择和设计。 商业机会：目标客户将是皮肤科医生，而Peak揭示了285万美元 预计以最低可能的上价价格预计，93％的患者支付≤25美元的自付费用。