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.
We propose to perform a clinical trial designed to test the efficacy of a promising investigational drug, latiglutenase, for alleviating the extraordinarily high burden of a gluten free diet that is experienced by patients with a dual diagnosis of Type 1 Diabetes (T1D) and celiac disease (CD).
