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

• 批准号: 10216393
• 负责人: David Matthew Maahs
• 金额: $ 97.76万
• 依托单位: IMMUNOGENICS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216393
• 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; Glycemic Index; Glycosylated hemoglobin A; Goals; 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; cohort; commercialization; comorbidity; diabetes management; diaries; disease diagnosis; drug candidate; dual diagnosis; effective therapy; efficacy study; efficacy testing; experience; gastrointestinal; glucose monitor; immunogenic; innovation; instrument; meetings; novel; operation; primary endpoint; programs; prospective; reduce symptoms; screening; seropositive; symptomatic improvement; therapeutic candidate; tool; trial design; type I diabetic

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.

这项工作的目的是评估治疗剂对保护1型个人的有效性 由于微小的摄入而遭受的肠道和有症状困扰的糖尿病（T1D）和乳糜泻（CD） 麸质蛋白。 T1D和CD都是终身自身免疫性疾病，其管理是锚定的 经过非常限制和不同的饮食。这两种疾病的合并症很高。而仅CD就会影响 在大多数国家，0.5-1％的一般人口，T1D患者的CD患病率是 估计约为6％。目前，唯一避免症状和可能长期症状的治疗选择 CD的健康后果是终身严格遵守无麸质饮食（GFD）。叠加时 在T1D患者中需要紧紧的血糖控制，疾病的燃烧是巨大的，特别是因为 许多市售无麸质食品具有高血糖指数。那是一个很大的未满足的 需要一种治疗溶液来减轻T1D和CD患者的GFD燃烧。 Immunogenx是一家临床阶段生物制药公司，开发治疗和诊断解决方案 对于CD。该公司的铅产品Latiglutenase是一种口服的双酶产品，可蛋白质溶解酶 面筋并显示了CD患者组织学保护和症状减轻的临床证据。 特别是，已经观察到证据证明了由于拉丁木素酶相对于安慰剂而导致的症状缓解 在遵守GFD的血清阳性欲望的CD患者中。根据这个sbir快速 Track（I阶段+II）提案，Immunogenx将与斯坦福大学的研究人员合作 T1D和CD专业知识以证明持续的血清阳性患者的症状缓解 T1D和CD。 斯坦福大学将对受试者进行双盲，安慰剂对照，随机绘制的研究 与T1D和CD保持血清阳性的CD特异性抗体，尽管试图维持 CD诊断后至少一年的GFD。除了为此临床提供latiglutenase 试验，免疫原还将提供最近验证的乳糜泻症状日记临床结果评估 （CDSDCOA）CD符号的仪器以及斯坦福试验的后勤支持。小说 在试验期间，尿液生物标志物将研究估计全身暴露于饮食面筋的情况。 我们的患者入学目标是基于降低症状的主要终点的足够动力。 我们预计需要预先筛选30名T1D和CD患者，以招募24例血清阳性患者 筛选期，最终达到了20个完整的患者。第一阶段将提供精致的试用设计， IRB批准以及试验准备活动，例如开发临床用品。实际审判 行为将发生在第二阶段。