Beyond the gluten-free diet: Innovations in celiac disease therapeutics

Table 1 Phase 2 studies exploring quantitative strategies in patients with celiac disease

NCT number	Study title	Study status (completion date)	Drug	Mechanism	Primary outcome measures	Sponsor	Phases
NCT01990885	Safety and systemic exposure study of BL-7010 in patients with well-controlled CD	Completed (October 2014)	BL-7010 vs placebo	BL-7010 interacts with α-gliadin and prevents the formation of immunogenic and cytotoxic peptides	Incidence of adverse events. For part 1, subjects were followed for up to 7 weeks from time of first administration. For part 2, subjects were followed for up to 4 weeks from time of first administration	BioLineRx, Ltd.	Phase 1, Phase 2
NCT03707730 AGY-010	A randomized, double-blind, placebo-controlled, crossover trial to evaluate safety and efficacy of AGY in CD	Unknown (December 2022)	AGY vs placebo	IgY antibody put into capsule form (AGY), produced from the egg yolks of superimmunized laying hens	Safety (adverse events, laboratory results, symptoms). tTGA levels measured at each visit. CD- related symptoms 14 weeks	Igy Inc.	Phase 2
NCT01917630	Evaluation of the efficacy and safety of ALV003 in symptomatic patients with CD	Completed (June 2015)	Latiglutenase (ALV003) vs placebo	ALV003 is a mixture of two recombinant gluten-specific proteases to contribute to the degradation of gluten into non-immunogenic fragments	Efficacy: Intestinal mucosal morphometry, change in Vh:Cd between baseline and week 12	Alvine Pharmaceuticals Inc.	Phase 2
NCT01255696	Safety and efficacy of varying methods of ALV003 administration for the treatment of CD	Completed (June 2011)	Latiglutenase (ALV003) vs placebo	ALV003 is a mixture of two recombinant gluten-specific proteases to contribute to the degradation of gluten into non-immunogenic fragments	Efficacy: Intestinal mucosal morphology. Safety: Tolerability of ALV003, safety evaluated at 6 weeks	Alvine Pharmaceuticals Inc.	Phase 2
NCT00959114	Safety and efficacy of ALV003 for the treatment of CD	Completed (October 2010)	Latiglutenase (ALV003)	ALV003 is a mixture of two recombinant gluten-specific proteases to contribute to the degradation of gluten into non-immunogenic fragments	Efficacy: Intestinal mucosal morphology. Safety: Tolerability of ALV003 at 6 weeks	Alvine Pharmaceuticals Inc.	Phase 2
NCT01255696	Safety and efficacy of ALV003 for the treatment of CD	Completed (June 2011)	Latiglutenase (ALV003)	ALV003 is a mixture of two recombinant gluten-specific proteases to contribute to the degradation of gluten into non-immunogenic fragments	Efficacy: Intestinal mucosal morphology. Safety: Tolerability of ALV003 at 6 weeks	Alvine Pharmaceuticals Inc.	Phase 2
NCT03585478	Latiglutenase (IMGX003) as a treatment for CD	Completed (January 22, 2021)	Latiglutenase (IMGX003) vs placebo	A combination of ALV001 and ALV002, a Sphingomonas capsulata PEP that degrade gluten proteins and reduces the immunogenic potential of gluten	The primary efficacy endpoint of this study is histologic protection as measured by EGD (Vh:Cd) at 6 weeks	Immunogenics, LLC	Phase 2
NCT04243551	Prospective, randomized, double-blind, placebo-controlled, crossover study of latiglutenase (IMGX003) in symptomatic patients with CD	Active, not recruiting (December 2023)	Latiglutenase vs placebo	A combination of ALV001 and ALV002, a Sphingomonas capsulata PEP that degrade gluten proteins and reduces the immunogenic potential of gluten	The primary efficacy endpoint of this study is the mean percent reduction in symptom severity relative to placebo at 6 months	Immunogenics, LLC	Phase 2
NCT04839575	Study of latiglutenase (IMGX003) in T1D/CD patients	Terminated (December 19 2022)	DRUG: Latiglutenase vs placebo	A combination of ALV001 and ALV002, a Sphingomonas capsulata PEP that degrade gluten proteins and reduces the immunogenic potential of gluten	The primary efficacy endpoint of this study is absolute mean reduction in symptom severity relative to placebo at 6 months	Immunogenics LLC	Phase 2
NCT05353985	A study of TAK-062 in treatment of active CD in participants attempting a gluten-free diet	Recruiting (May 6, 2025)	TAK-062 with or without simulated inadvertent gluten exposure gluten-bar	Third-generation enzyme with the ability to degrade > 99% of gluten and gluten peptides	Change in weekly CD symptom diary gastrointestinal symptom severity score from baseline (week 1) to week 12	Takeda	Phase 2
NCT00810654	Effect of Aspergillus Niger prolyl endoprotease (AN-PEP) enzyme on the effects of gluten ingestion in patients with CD	Completed (2009-12)	AN-PEP 160 PPU daily for 2 weeks	An enzyme that degrades both whole gluten and gluten peptides into non-immunogenic residues within minutes	Histopathological changes according to the modified marsh criteria. The presence of CD-specific antibodies (EMA, tTGA, gliadin) (1 week before start, and 2 and 6 weeks after start)	Amsterdam UMC, location VUmc	Phase 1, phase 2

AN-PEP: Aspergillus Niger prolyl endoprotease; CD: Celiac disease; EGD: Esophagogastroduodenoscopy; EMA: Endomysial antibodies; IgY: Avian immunoglobulin Y; PEP: Prolyl endopeptidase; T1D: Type 1 diabetes; tTGA: Tissue transglutaminase IgA; Vh:Cd: Villous height to crypt depth ratio.