A Clinical Study of Latiglutenase as a Treatment for Symptom Reduction for Celiac Disease

Project Summary AbstractThe goal of this work is to develop a therapeutic drug that will protect individuals with celiac diseaseCDfrom intestinal and symptomatic distress they suffer due to minute ingestion of gluten proteinCD is an autoimmune disorder affecting the small intestineafflicting aboutof the world s populationfor which there is no known cureCurrently the only therapeutic option to avoid gastrointestinal related symptoms and potentially long term health consequences is the life long strict adherence to a gluten free dietGFDHowevera majority of patients never fully recoverFurthermorerecent published analyses indicate that CD patients on average continue to inadvertently consume unsafe levels of gluten while attempting to adhere to a GFDRefThere is a considerable unmet need for a therapeutic solution to be used as an adjunct to a GFDImmunogenX is a clinical stage biopharmaceutical company developing therapeutic and diagnostic solutions for celiac diseaseOur lead developmentlatiglutenaseis an orally administered enzyme product with clinical evidence for histologic protection and symptomatic reduction in CD patientsThe FDAin Type C meetings with ImmunogenXsupports the company s trial strategysymptom labeland outcome measuring instrumentImmunogenX s team has extensive experience in clinical development and operationsregulatory affairsbiostatisticsand marketing strategyLatiglutenasea dual enzyme drug producthas a strong scientific premise to justify further clinical testingPrevious clinical trials have yielded encouraging but inconclusive information regarding its impact on improving mucosal healthThe indeterminacy is mostly attributable to shortcomings in one of the trial designs that became evident upon review of the trial resultsMucosal healing is relatively slow to manifestMuch stronger evidence was observed for symptom relief due to latiglutenase relative to placebohoweverthis benefit was almost exclusively found in a subpopulation of CD patients who remained seropositive despite adhering to a GFDWe are beginning to better understand the reasons for this selectivity and also gaining more understanding of the prevalence of persistent seropositivity while on a GFDThe proposed NIAID trial will focus on multiple symptom relief for this subpopulation of CD patientswhich comprises approximatelyof all CD patientsIn this SBIR Fast TrackPhase I IIUproposalwe propose a randomizeddouble blindplacebo controlleddose ranging crossover study for diagnosed CD patients who remain symptomatic despite adhering to a gluten free dietOur enrollment target is based on adequate powering of the primary endpoint for symptom reductionWe anticipate the need to prescreenpatients to enrollseropositive patients into the screening periodaboutof CD patients afteryear on a GFD remain persistently seropositiveultimately achievingcompleted patientsSubject recruitment will involve four study centers and will span approximatelymonthsWe will employ the recently validated Celiac Disease Symptom Diary patientreported outcomeCDSDPROinstrument for CD symptomsPhase I will provide a refined trial designoutcome measurement developmentstatistical toolsand final drug product development to justify clinical trial conduct in Phase IIProject NarrativeThis work will provide refined trial designoutcome measurement developmentstatistical toolsetcSBIR Phase Ito inform us on an optimal clinical trial design to demonstrate latiglutenase as a therapeutic solution for symptomatic treatment of celiac diseaseCDpatientsSBIR Phase IIThe primary endpoint will be statistically significant symptomatic improvement relative to placebo for seropositive CD patients as measured using a validated patient reported outcomePROinstrument