A Clinical Study of Latiglutenase as a Treatment for Type 1 Diabetics with Celiac Disease

Latiglutenase 治疗 1 型糖尿病合并乳糜泻的临床研究

基本信息

批准号：
10255820
负责人：
David Matthew Maahs
金额：
$ 93.36万
依托单位：
IMMUNOGENICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-08 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10255820
关键词：
Abdominal Pain Adherence Affect Animals Antibodies Assessment tool Autoimmune Diseases Biological Assay Biological Markers Biological Products Biometry Blood Glucose Bread Celiac Disease Clinical Clinical Research Clinical Trials Clinical Trials Design Country Data Databases Development Diagnosis Diagnostic Diet Disease Distress Documentation Double-Blind Method Eligibility Determination Enrollment Enzymes Exposure to Food Food Chain Funding General Population Genes Glucose Gluten Gluten-free diet Glycemic Index Glycosylated hemoglobin A Goals HLA-DQ2 Health Histologic Immune system Individual Ingestion Inherited Institutional Review Boards Insulin Insulin-Dependent Diabetes Mellitus Intestinal Diseases Intestines Investigational Drugs Label Lead Life Logistics Marketing Masks Measurement Measures Modeling Monitor Oral Outcome Outcome Assessment Outcome Measure Pancreas Patients Peptides Pharmaceutical Preparations Phase Placebos Population Preparation Prevalence Proteins Randomized Regulatory Affairs Research Design Research Personnel Running Safety Secure Slice Small Business Innovation Research Grant Small Intestines Stomach Structure of beta Cell of islet Symptoms Therapeutic Therapeutic Agents Time Universities Urine Withdrawal Work base burden of illness clinical development clinical efficacy clinical outcome assessment cohort commercialization comorbidity diabetes management diaries dietary disease diagnosis drug candidate dual diagnosis effective therapy efficacy evaluation efficacy study efficacy testing experience gastrointestinal glucose monitor immunogenic innovation instrument meetings novel operation participant enrollment primary endpoint programs prospective reduce symptoms screening seropositive symptomatic improvement therapeutic candidate tool trial design type I diabetic

项目摘要

The goal of this work is to evaluate the efficacy of a therapeutic agent for protecting individuals with Type 1 diabetes (T1D) and celiac disease (CD) from intestinal and symptomatic distress they suffer due to minute ingestion of gluten protein. Both T1D and CD are lifelong autoimmune diseases whose management is anchored upon very restrictive and distinct diets. The co-morbidity of these two diseases is high; whereas CD alone affects 0.5-1% of the general population in most countries, the prevalence of CD among patients with T1D has been estimated to be ~6%. Currently the only therapeutic option to avoid the symptoms and potentially long-term health consequences of CD is the life-long strict adherence to a gluten-free diet (GFD). When superimposed on the need for tight blood sugar control in a T1D patient, the burden of disease is enormous especially because many commercially available gluten-free foods have high glycemic indices. Thus, there is a considerable unmet need for a therapeutic solution to alleviating the burden of a GFD in patients with both T1D and CD. ImmunogenX is a clinical-stage biopharmaceutical company developing therapeutic and diagnostic solutions for CD. The company’s lead product, latiglutenase, is an orally administered, dual-enzyme product that proteolyzes gluten and shows clinical evidence for histologic protection and symptomatic reduction in CD patients. In particular, evidence has been observed for symptom relief due to latiglutenase relative to placebo in a subpopulation of CD patients who remained seropositive despite adhering to a GFD. Accordingly, in this SBIR Fast Track (Phase I+II) proposal, ImmunogenX will team up with researchers at Stanford University who have extensive T1D and CD expertise to demonstrate symptom relief in persistently seropositive patients with a diagnosis of both T1D and CD. The Stanford team will conduct a double-blind, placebo-controlled, randomized-withdrawal study on subjects with T1D and CD who remain seropositive for CD-specific antibodies notwithstanding attempts to maintain a GFD for at least one year following their CD diagnosis. In addition to supplying latiglutenase for this clinical trial, ImmunogenX will also provide the recently validated Celiac Disease Symptom Diary clinical outcome assessment (CDSD© COA) instrument for CD symptoms as well as logistical support for the Stanford trial. A novel urine biomarker will be studied to estimate systemic exposure to dietary gluten over the duration of the trial. Our patient enrollment target is based on adequate powering of the primary endpoint for symptom reduction. We anticipate the need to prescreen 30 patients with both T1D and CD to enroll 24 seropositive patients into the run-in screening period, ultimately achieving 20 completed patients. Phase I will provide a refined trial design, IRB approvals as well as trial preparation activities such as development of clinical supplies. The actual trial conduct will occur in Phase II.

这项工作的目标是评估治疗剂对保护 1 型患者的功效糖尿病 (T1D) 和乳糜泻 (CD) 由于肠道和症状不适而遭受微量摄入 T1D 和 CD 都是终生自身免疫性疾病，其治疗是固定的。这两种疾病的共同发病率很高，而 CD 单独影响；在大多数国家，1 型糖尿病患者中 CD 的患病率占总人口的 0.5-1% 估计约为 6%，目前是避免症状并可能长期存在的唯一治疗选择。 CD 的健康后果是终身严格遵守无麸质饮食 (GFD)。 T1D 患者需要严格控制血糖，疾病负担是巨大的，特别是因为许多市售无麸质食品的血糖指数很高，因此，还有相当大的未满足。需要一种治疗方案来减轻 T1D 和 CD 患者的 GFD 负担。 ImmunogenX 是一家临床阶段的生物制药公司，开发治疗和诊断解决方案该公司的主导产品 latiglutenase 是一种口服双酶产品，可进行蛋白水解。麸质，并显示了 CD 患者的组织学保护和症状减轻的临床证据。特别是，在亚人群中观察到拉谷蛋白酶相对于安慰剂所导致的症状缓解的证据尽管坚持 GFD，CD 患者仍保持血清反应阳性，因此，在本次 SBIR Fast 中。 Track（I+II 期）提案，ImmunogenX 将与斯坦福大学的研究人员合作，他们在 T1D 和 CD 专业知识可证明诊断后持续血清阳性患者的症状缓解 T1D 和 CD 都有。斯坦福大学团队将对受试者进行双盲、安慰剂对照、随机 Willowal 研究患有 T1D 和 CD 的患者，尽管尝试维持 CD 特异性抗体，但仍保持血清阳性 CD 诊断后至少一年的 GFD 除了为此临床提供拉谷蛋白酶外。试验中，ImmunogenX 还将提供最近验证的乳糜泻症状日记临床结果评估 (CDSD© COA) 用于诊断 CD 症状的工具以及为斯坦福试验提供后勤支持的新型工具。将研究尿液生物标志物，以估计试验期间膳食麸质的全身暴露量。我们的患者入组目标是基于对减轻症状的主要终点的充分支持。我们预计需要对 30 名同时患有 T1D 和 CD 的患者进行预筛查，以将 24 名血清反应呈阳性的患者纳入研究中。磨合筛选期，最终完成 20 名患者，第一阶段将提供完善的试验设计， IRB 批准以及临床用品开发等试验准备活动实际试验。行为将发生在第二阶段。