Study to Assess the Efficacy of Larazotide Acetate for the Treatment of Celiac Disease

Study Overview
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Brief Summary
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This study was conducted to evaluate the efficacy of multiple doses of larazotide acetate in preventing intestinal permeability changes induced by a 6- week gluten challenge in subjects with celiac disease.

Detailed Description
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This was a Phase IIb, randomized, double-blind, placebo-controlled, dose ranging, multicenter Study to determine the safety, tolerance, and efficacy of larazotide acetate in subjects with celiac disease during a gluten challenge. Subjects remained on their gluten-free diet throughout the duration of the trial. Study drug or drug placebo capsules were administered TID 15 minutes before each meal. Gluten or gluten placebo capsules will be taken TID with each meal.

Official Title
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A Phase IIb, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Multicenter Study to Determine the Safety, Tolerance, and Efficacy of Larazotide Acetate (AT-1001) in Celiac Disease Subjects During a Gluten Challenge

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: larazotide acetate
* Drug: placebo
* Dietary Supplement: 900 mg gluten


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults with biopsy proven celiac disease on a gluten-free diet for at least the past 6 months Anti-Tissue Transglutaminase (anti-tTG) ≤ 10 EU. BMI between 18.5 and 38, inclusive. Exclusion Criteria Has chronic active GI disease other than celiac disease Has diabetes (Type 1 or Type 2). Unable to abstain from alcohol consumption or NSAID use for 48 hours prior to each intestinal permeability collection throughout the study. Has hemoglobin value below 8.5 g/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo Controlled, dose ranging, multicenter Study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Larazotide acetate 1 mg<br>larazotide acetate 1 mg capsules TID + 900 mg gluten capsules TID for 6 weeks | Drug: larazotide acetate<br>* gelatin capsules<br>* Other names: INN-202;Dietary Supplement: 900 mg gluten<br>* gelatin capsules<br>|
| Experimental: Larazotide acetate 4 mg<br>larazotide acetate 4 mg capsules TID + 900 mg gluten capsules TID for 6 weeks | Drug: larazotide acetate<br>* gelatin capsules<br>* Other names: INN-202;Dietary Supplement: 900 mg gluten<br>* gelatin capsules<br>|
| Experimental: Larazotide acetate 8 mg<br>larazotide acetate 8 mg capsules TID + 900 mg gluten capsules TID for 6 weeks | Drug: larazotide acetate<br>* gelatin capsules<br>* Other names: INN-202;Dietary Supplement: 900 mg gluten<br>* gelatin capsules<br>|
| Placebo Comparator: Placebo<br>placebo capsules TID + 900 mg gluten capsules TID for 6 weeks | Drug: placebo<br>* gelatin capsules<br>Dietary Supplement: 900 mg gluten<br>* gelatin capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of multiple doses larazotide acetate in preventing intestinal permeability changes induced by a 6- week gluten challenge. | The primary efficacy endpoint was the Day 49 to Day 7 ratio of urinary LAMA ratios as a response to gluten | Following ingestion of a solution of lactulose and mannitol; lactulose and mannitol excretion was quantified and the LAMA ratio calculated from overnight urine specimens collected on Days 7, 21, 35, 49 and 56. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of a 6-week exposure to oral doses of larazotide acetate in celiac disease patients exposed to 900 mg gluten TID with meals | Safety endpoints assessed in this study were adverse events, vital signs, physical examination results, clinical laboratory test results, concomitant medication usage and ECG results | Up to 6 weeks | 
| To prospectively validate a composite, weighted index of celiac disease activity | Gastrointestinal symptoms were assessed by the GSRS patient self-assessment questionnaire | GSRS was completed weekly throughout the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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larazotide acetate