The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Joseph A. Murray - One of the best experts on this subject based on the ideXlab platform.
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The potential utility of tight junction regulation in celiac disease: focus on Larazotide acetate
Therapeutic advances in gastroenterology, 2015Co-Authors: Shahryar Khaleghi, Abhinav Lamba, Joseph A. MurrayAbstract:Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that Larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.
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929b Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controll
Gastroenterology, 2014Co-Authors: Chao Wang, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Daniel A. Leffler, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Premysl Bercik, Joseph A. MurrayAbstract:Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controlled Trial Chao Wang, Henrik Rasmussen, Wendy Perrow, Ciaran P. Kelly, Daniel Le7ffler, Peter Green, Richard N. Fedorak, Anthony J. DiMarino, Premysl Bercik, Joseph A. Murray, Natalie M. Bachir
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge a randomised placebo controlled study
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo‐controlled study
Alimentary pharmacology & therapeutics, 2012Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
The American journal of gastroenterology, 2012Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Anthony M. Colatrella, Francisco León, H Z Abdallah, Lucinda A. Harris, L. A. Arterburn, B. M. Paterson, Z H Lan, Joseph A. MurrayAbstract:A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
Daniel A. Leffler - One of the best experts on this subject based on the ideXlab platform.
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Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial
Gastroenterology, 2015Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Chao Wang, Premysl Bercik, Natalie M. BachirAbstract:Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed Larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of Larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P = .017), a 31% increase in improved symptom days ( P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.
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929b Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controll
Gastroenterology, 2014Co-Authors: Chao Wang, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Daniel A. Leffler, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Premysl Bercik, Joseph A. MurrayAbstract:Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controlled Trial Chao Wang, Henrik Rasmussen, Wendy Perrow, Ciaran P. Kelly, Daniel Le7ffler, Peter Green, Richard N. Fedorak, Anthony J. DiMarino, Premysl Bercik, Joseph A. Murray, Natalie M. Bachir
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge a randomised placebo controlled study
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo‐controlled study
Alimentary pharmacology & therapeutics, 2012Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
The American journal of gastroenterology, 2012Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Anthony M. Colatrella, Francisco León, H Z Abdallah, Lucinda A. Harris, L. A. Arterburn, B. M. Paterson, Z H Lan, Joseph A. MurrayAbstract:A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
Ciaran P. Kelly - One of the best experts on this subject based on the ideXlab platform.
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Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial
Gastroenterology, 2015Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Chao Wang, Premysl Bercik, Natalie M. BachirAbstract:Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed Larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of Larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P = .017), a 31% increase in improved symptom days ( P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.
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929b Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controll
Gastroenterology, 2014Co-Authors: Chao Wang, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Daniel A. Leffler, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Premysl Bercik, Joseph A. MurrayAbstract:Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controlled Trial Chao Wang, Henrik Rasmussen, Wendy Perrow, Ciaran P. Kelly, Daniel Le7ffler, Peter Green, Richard N. Fedorak, Anthony J. DiMarino, Premysl Bercik, Joseph A. Murray, Natalie M. Bachir
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge a randomised placebo controlled study
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo‐controlled study
Alimentary pharmacology & therapeutics, 2012Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
The American journal of gastroenterology, 2012Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Anthony M. Colatrella, Francisco León, H Z Abdallah, Lucinda A. Harris, L. A. Arterburn, B. M. Paterson, Z H Lan, Joseph A. MurrayAbstract:A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
Francisco León - One of the best experts on this subject based on the ideXlab platform.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge a randomised placebo controlled study
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo‐controlled study
Alimentary pharmacology & therapeutics, 2012Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
The American journal of gastroenterology, 2012Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Anthony M. Colatrella, Francisco León, H Z Abdallah, Lucinda A. Harris, L. A. Arterburn, B. M. Paterson, Z H Lan, Joseph A. MurrayAbstract:A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge
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Non-dietary therapeutic clinical trials in coeliac disease.
European journal of internal medicine, 2011Co-Authors: Laura Crespo Pérez, Gemma Castillejo De Villasante, Ana Cano Ruiz, Francisco LeónAbstract:Abstract Coeliac disease is a permanent immunological intolerance to gluten proteins in genetically predisposed individuals. The only management is life-long strict adherence to a gluten-free diet. Unfortunately, compliance with gluten-free diet is very difficult in practice due to the widespread presence of gluten in Western diets. For this reason, about 50% of coeliacs following a gluten-free diet continue to suffer from symptoms and present with autoantibodies and/or villous atrophy while on a gluten-free diet. It is therefore important to explore new therapies to improve the management of coeliac disease. To date, five experimental therapies have been tested in randomized and controlled clinical trials. Larazotide acetate reduces the para-cellular passage of gluten to the lamina propria by preventing the opening of intercellular tight junctions. The endopeptidases ALV003 and AN-PEP break down gluten to produce less or non-toxic peptide fragments. A therapeutic vaccine is being tested with the aim of developing gluten tolerance. Finally, infection with the nematode Necator americanus and treatment with the CCR9 antagonist Traficet-EN have also been reported. While substantial progress has been made in the last few years, it is important to remember that all these investigational therapies are in research stage and are generally being considered as “adjunctive” therapies to the gluten-free diet and not as substitutes of the gluten-free diet at this point in time.
Anthony J. Dimarino - One of the best experts on this subject based on the ideXlab platform.
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Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial
Gastroenterology, 2015Co-Authors: Daniel A. Leffler, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Chao Wang, Premysl Bercik, Natalie M. BachirAbstract:Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed Larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of Larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P = .017), a 31% increase in improved symptom days ( P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov: NCT01396213.
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929b Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controll
Gastroenterology, 2014Co-Authors: Chao Wang, Ciaran P. Kelly, Peter H.r. Green, Anthony J. Dimarino, Daniel A. Leffler, Richard N. Fedorak, Wendy Perrow, Henrik S. Rasmussen, Premysl Bercik, Joseph A. MurrayAbstract:Larazotide Acetate, a First In-Class, Novel Tight Junction Regulator, Meets Primary Endpoint and Significantly Reduces Signs and Symptoms of Celiac Disease in Patients on a Gluten-Free Diet: Results of a Multicenter, Randomized, Placebo Controlled Trial Chao Wang, Henrik Rasmussen, Wendy Perrow, Ciaran P. Kelly, Daniel Le7ffler, Peter Green, Richard N. Fedorak, Anthony J. DiMarino, Premysl Bercik, Joseph A. Murray, Natalie M. Bachir
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge a randomised placebo controlled study
Alimentary Pharmacology & Therapeutics, 2013Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo‐controlled study
Alimentary pharmacology & therapeutics, 2012Co-Authors: Ciaran P. Kelly, Peter H.r. Green, Joseph A. Murray, Anthony J. Dimarino, Anthony M. Colatrella, Daniel A. Leffler, Thomas J. Alexander, Razvan Arsenescu, Francisco León, John JiangAbstract:Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of Larazotide acetate during gluten challenge. Methods This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to Larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between Larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the Larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between Larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between Larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
