Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated randomised, double-blind, placebo-controlled phase 2 study

Tye–Din, Jason A.; Daveson, James; Goel, Gautam; Goldstein, Kaela E.; Hand, Holly L; Neff, Kristin M; Popp, Alina; Taavela, Juha; Mäki, Markku; Isola, Jorma; Williams, Leslie; Truitt, Kenneth E.; Adams, Atoya; Andrews, Jane M.; Mei, Swee Lin Chen Yi; Coates, Allan G.; DiMarino, Anthony J.; Ee, Hooi C.; Elliott, David E.; Epstein, Roger; Feyen, Bryan John; Fogel, Ronald; Friedenberg, Keith; Gearry, Richard; Gerdis, Michael S; Goldstein, Michael J.; Gupta, Vipin; Holmes, R.; Holtmann, Gerald; Idarraga, Samuel H; James, G.; King, Tim; Klein, Terry D; Kupfer, Sonia S.; Lebwohl, Benjamin; Lowe, Matthew John; Murray, Joseph A.; Newton, Eric; Quinn, Dean; Radin, David M; Ritter, Timothy E.; Stacey, Helen Lee; Strout, Cynthia; Stubbs, Richard S.; Thackwray, Susan Lynn; Trivedi, Vivek M; Weber, John R; Wilson, Scott

doi:10.1016/s2468-1253(22)00428-9

Cited by 18 publications

(3 citation statements)

References 28 publications

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“…However, with stepwise dose escalation, there were no differences in symptoms between the Nexvax2 group and the placebo [127]. In a phase 2, randomized, doubleblind, placebo-controlled clinical study, Nexvax2 was stopped after an interim analysis showed that Nexvax2 did not provide statistically significant protection from gluteninduced symptoms [128].…”

Section: Immuno Tolerance Promotionmentioning

confidence: 99%

Emerging Pharmaceutical Therapies to Address the Inadequacy of Gluten-Free Diet for Celiac Disease

Crepaldi,

Palo,

Maniero

et al. 2023

Preprint

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.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

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Section: Immuno Tolerance Promotionmentioning

confidence: 99%

Emerging Pharmaceutical Therapies to Address the Inadequacy of Gluten-Free Diet for Celiac Disease

Crepaldi,

Palo,

Maniero

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…However, with stepwise dose escalation, there were no differences in symptoms between the Nexvax2 group and the placebo [ 127 ]. In a phase 2, randomized, double-blind, placebo-controlled clinical study, Nexvax2 was stopped after an interim analysis showed that Nexvax2 did not provide statistically significant protection from gluten-induced symptoms [ 128 ].…”

Section: Potential Therapeutic Targets In Celiac Diseasementioning

confidence: 99%

Emerging Pharmaceutical Therapies to Address the Inadequacy of a Gluten-Free Diet for Celiac Disease

Crepaldi,

Palo,

Maniero

et al. 2023

Pharmaceuticals

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Celiac disease (CeD) is a chronic autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environmental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist despite apparent compliance with a GFD. This could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on a GFD who experience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This review will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

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“…The first therapy aiming to induce immune tolerance in CD to enter Phase 2 trials, Nexvax2, consisted of an adjuvant‐free gluten peptide mix 96 . While injections of Nexvax2 into CD participants modified T cell responses to these gluten peptides, treatment did not translate into protection from symptoms induced by a large oral dose of gluten.…”

Section: Introductionmentioning

confidence: 99%

Evolution in coeliac disease diagnosis and management

Tye‐Din

2024

JGH Open

Self Cite

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The traditional gut‐centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease ‐ well demonstrated in children ‐ are growing for adults. Novel biomarkers such as interleukin‐2 that identify the gluten‐specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case‐finding strategy and enthusiasm for population screening is growing. The gluten‐free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly‐responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super‐sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.

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Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated randomised, double-blind, placebo-controlled phase 2 study

Cited by 18 publications

References 28 publications

Emerging Pharmaceutical Therapies to Address the Inadequacy of Gluten-Free Diet for Celiac Disease

Emerging Pharmaceutical Therapies to Address the Inadequacy of Gluten-Free Diet for Celiac Disease

Emerging Pharmaceutical Therapies to Address the Inadequacy of a Gluten-Free Diet for Celiac Disease

Evolution in coeliac disease diagnosis and management

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