A novel diagnostic Kit for Hepatocellular Carcinoma

一种新型肝细胞癌诊断试剂盒

• 批准号: 10670881
• 负责人: Xuanyong Lu
• 金额: $ 128.9万
• 依托单位: IMCARE BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670881
• 关键词: Address; Award; Biological Markers; Biopsy; Biotechnology; Blood; Blood specimen; Cessation of life; Chronic; Chronic Hepatitis B; Cirrhosis; Clinical; Clinical Research; Data; Data Analyses; Development; Diagnosis; Diagnostic Reagent Kits; Disease; Early Diagnosis; Early treatment; Enrollment; Ensure; Enzyme-Linked Immunosorbent Assay; Excision; Goals; Hepatitis B Virus; Hepatitis C; Image; Imaging technology; Incidence; Individual; Letters; Liver Cirrhosis; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Malignant Epithelial Cell; Malignant neoplasm of liver; Marketing; Medical Device; Monoclonal Antibodies; Outcome; Pancreatitis; Patients; Performance; Phase; Physicians; Primary carcinoma of the liver cells; Prognosis; Proteins; Prothrombin; Radiofrequency Interstitial Ablation; Recommendation; Relative Risks; Research Personnel; Risk; Risk Assessment; Sample Size; Screening for Hepatocellular Cancer; Sensitivity and Specificity; Serine Proteinase Inhibitors; Serum; Small Business Innovation Research Grant; Specificity; Surveillance Methods; Survival Rate; Technology; Testing; Time; Universities; Use Effectiveness; Viral; alpha-Fetoproteins; chronic liver disease; commercialization; cost; curative treatments; design; diagnostic platform; disorder risk; effective therapy; high risk; improved; liver transplantation; medical schools; minimally invasive; novel diagnostics; phase 2 study; primary endpoint; prospective; secondary endpoint; surveillance study; tool; tumor; ultrasound

PROJECT SUMMARY ImCare Biotech is seeking to commercialize Seravue®, an ELISA-based diagnostic system that is able to identify both early and late stage Hepatocellular Carcinoma (HCC) with high sensitivity and specificity. With NCI- supported Phase I and II SBIR awards plus internal and external investor support, ImCare completed the technical development of the Seravue® product and now requests Phase IIB SBIR support to conduct a prospective clinical study required for a 510(k) filing and subsequent regulatory clearance. Commercialization of Seravue® has the potential to substantially improve early detection of HCC in patients undergoing surveillance due to high-risk conditions, thereby ensuring timely, effective treatment and greatly increasing survival. HCC, the most common and deadliest form of liver cancer, has a 5-year survival rate of less than 15% and is directly responsible for hundreds of thousands of deaths worldwide each year. HCC is typically diagnosed at a late stage when treatments are largely ineffective, resulting in poorer prognosis, but early diagnosis and treatment can increase 5-year survival rates to >70%. Thus, individuals known to be at high risk for HCC—including patients with liver cirrhosis or chronic hepatitis B/C—undergo HCC surveillance every 3 to 6 months to improve the chances of catching the disease early. Current surveillance methods have significant drawbacks including cost, burden, poor detection of early disease, and inadequate sensitivity and specificity. To address the need for a better surveillance tool, we developed Seravue®, a minimally-invasive, accurate, consistent, and inexpensive test for Liver Cancer-Serine Protease Inhibitor Kazal (LC-SPIK), a protein specifically secreted by HCC cells. In Phase I and Phase II studies, ImCare confirmed two critical features of Seravue®: 1) It distinguishes HCC from other liver diseases, non-liver diseases, and healthy subjects and 2) it is significantly more sensitive and specific than alpha fetoprotein (AFP), the most common biomarker test for HCC. In this Phase IIB SBIR, ImCare proposes to conduct a clinical study to support a 510(k) filing for the clearance of Seravue® as class II medical device. Aim 1. Demonstrate the feasibility and effectiveness of using serum levels of LC-SPIK to assess the risk of developing HCC for patients with chronic liver disease. Per FDA guidance, the blood biomarker DCP will be used as the primary predicate. Primary Endpoints: Sensitivity and specificity compared to DCP. Secondary Endpoint: Calculated relative risk of developing HCC compared to DCP. Aim 2. Pursue CMS reimbursement and submit a 510(k) application. Milestones: 1) Additional requirements for CMS reimbursement identified and 2) 510(k) filing submitted. Impact: Successful completion of these milestones is expected to support FDA clearance of Seravue®, which will provide an early detection and surveillance tool for HCC that provides better efficacy, lower cost, and lower burden than current tools. Commercialization of Seravue® is expected to save lives by increasing early detection.

项目概要 ImCare Biotech 正在寻求 Seravue® 的商业化，这是一种基于 ELISA 的诊断系统，能够 具有高敏感性和特异性来识别早期和晚期肝细胞癌 (HCC)。与 NCI- 在 I 期和 II 期 SBIR 奖项的支持以及内部和外部投资者的支持下，ImCare 完成了 Seravue® 产品的技术开发，现在请求 IIB SBIR 支持以进行 510(k) 备案和后续监管审批所需的前瞻性临床研究。商业化 Seravue® 有潜力显着改善接受化疗的患者的 HCC 早期检测 对高危情况进行监测，从而确保及时、有效的治疗，并极大地提高治疗效果。 提高生存率。 HCC 是最常见和最致命的肝癌形式，其 5 年生存率为 不到 15%，每年直接导致全球数十万人死亡。肝癌是 通常在晚期诊断时，治疗基本上无效，导致预后较差，但 早期诊断和治疗可以将5年生存率提高到>70%。因此，已知处于高位的人 HCC 风险（包括肝硬化或慢性乙型/丙型肝炎患者）每 3 次接受 HCC 监测 至 6 个月，以提高早期感染该疾病的机会。目前的监测方法具有重要意义 缺点包括成本、负担、早期疾病检测不佳以及敏感性和特异性不足。到 为了满足对更好监测工具的需求，我们开发了 Seravue®，一种微创、准确、 对肝癌丝氨酸蛋白酶抑制剂 Kazal (LC-SPIK)（一种蛋白质）进行一致且廉价的测试 由肝癌细胞特异性分泌。在 I 期和 II 期研究中，ImCare 证实了两个关键特征 Seravue®：1) 它将 HCC 与其他肝病、非肝病和健康受试者区分开来，2) 它 比甲胎蛋白（AFP）（最常见的生物标志物测试）更敏感和特异。 肝癌。在此 IIB SBIR 阶段，ImCare 提议进行一项临床研究，以支持 510(k) 申请 Seravue® 被批准为 II 类医疗器械。目标1.证明使用的可行性和有效性 LC-SPIK 的血清水平可评估慢性肝病患者发生 HCC 的风险。根据 FDA 指导下，血液生物标志物 DCP​​ 将用作主要谓词。主要终点：敏感性和 与 DCP 相比的特异性。次要终点：计算出与 DCP 相比发生 HCC 的相对风险。 目标 2. 寻求 CMS 报销并提交 510(k) 申请。里程碑： 1) 附加要求 确定 CMS 报销并提交 2) 510(k) 备案。影响：成功完成这些里程碑 预计将支持 FDA 批准 Seravue®，这将提供早期检测和监测工具 与现有工具相比，针对 HCC 提供更好的疗效、更低的成本和更低的负担。商业化 Seravue® 有望通过增加早期检测来拯救生命。

项目成果

Screening and identification of compounds with antiviral activity against hepatitis B virus using a safe compound library and novel real-time immune-absorbance PCR-based high throughput system.

• DOI: 10.1016/j.antiviral.2013.02.001
• 发表时间: 2013-04
• 期刊: ANTIVIRAL RESEARCH
• 影响因子: 7.6
• 作者: Lamontagne, Jason;Mills, Courtney;Mao, Richeng;Goddard, Cally;Cai, Dawei;Guo, Haitao;Cuconati, Andy;Block, Timothy;Lu, Xuanyong
• 通讯作者: Lu, Xuanyong

Liver Cancer-Specific Serine Protease Inhibitor Kazal Is a Potentially Novel Biomarker for the Early Detection of Hepatocellular Carcinoma.

• DOI: 10.14309/ctg.0000000000000271
• 发表时间: 2020-12
• 期刊: Clinical and translational gastroenterology
• 影响因子: 3.6
• 作者: Lu F;Shah PA;Rao A;Gifford-Hollingsworth C;Chen A;Trey G;Soryal M;Talat A;Aslam A;Nasir B;Choudhry S;Ishtiaq R;Sanoff H;Conteh LF;Noonan A;Hu KQ;Schmidt C;Fu M;Civan J;Xiao G;Lau DT;Lu X
• 通讯作者: Lu X