A Double-blind Placebo-controlled Study to Evaluate Larazotide Acetate for the Treatment of Celiac Disease

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled Phase 2B study to evaluate the efficacy and safety of Larazotide Acetate in the treatment of patients with celiac disease who have persistent symptoms despite being on a gluten-free diet.

Detailed Description
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This is a double-blind, placebo-controlled Phase 2B study to evaluate the efficacy and safety of three different doses (0.5, 1 and 2 mg TID) of Larazotide Acetate as an adjunct to gluten-free diet in the treatment of patients with celiac disease (CD). The diagnosis of CD must have been established by jejunal biopsy as well as serology at some point in time prior to entry into the study. Patients must have symptoms despite being on a gluten-free diet as defined by a celiac disease domain of the gastrointestinal symptoms rating scale equal to or more than 2.0.

Official Title
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A Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Different Doses of Larazotide Acetate for the Treatment of Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: Larazotide Acetate
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults with biopsy proven and serology-confirmed celiac disease on a gluten-free diet for at least 12 months measurable serology at screening CeD GSRS score of ≥ 2.0 prior to randomization experiencing symptoms (ie, diarrhea, abdominal pain, bloating, nausea, or stomachache) willing to maintain current diet gluten-free diet throughout the duration of the study. Exclusion Criteria: refractory celiac disease or severe complications of celiac disease (eg, EATL, ulcerative jejunitis, perforation, etc.) chronic active GI disease other than celiac disease diabetes (Type 1 or 2) or other autoimmune disease that might interfere with the conduct of the study hemoglobin value < 8.5 g/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Larazotide Acetate 0.5 mg<br>larazotide acetate 0.5 mg capsules TID | Drug: Larazotide Acetate<br>* gelatin capsule<br>* Other names: INN-202;|
| Experimental: Larazotide Acetate 1 mg<br>larazotide acetate 1 mg capsules TID | Drug: Larazotide Acetate<br>* gelatin capsule<br>* Other names: INN-202;|
| Experimental: Larazotide Acetate 2 mg<br>larazotide acetate 2 mg capsules TID | Drug: Larazotide Acetate<br>* gelatin capsule<br>* Other names: INN-202;|
| Placebo Comparator: Placebo<br>placebo capsules TID | Drug: placebo<br>* gelatin capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of larazotide acetate versus placebo for the treatment of celiac disease in adults as an adjunct to a gluten-free diet | The primary efficacy endpoint was average on-treatment (Baseline to Week 12) score of theCeliac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS). | CeD GSRS was completed weekly Baseline through the end of 12-week double-blind treatment period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of larazotide acetate in subjects with active celiac disease | 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 12 weeks | 
| Validate a CeD PRO diary instrument in subjects with celiac disease | The CeD PRO is a 12-item questionnaire that was developed to assess symptom severity in clinical trials in subjects with celiac disease. Items in the questionnaire were formulated based on one-on-one interviews with subjects with celiac disease and thus reflect the symptoms that subjects consider part of their celiac disease experience. Subjects rated their symptom severity on an 11-point (0-10) scale. Symptoms included abdominal cramping, abdominal pain, bloating, constipation, diarrhea, gas, loose stools, nausea, vomiting, headache, and tiredness. The questionnaire was designed as a self-administered daily diary, to be completed at the same time each day, and required < 10 minutes to complete. | The CeD PRO was administered daily throughout the study. | 
| Compare various efficacy endpoints during 12 weeks of double-blind treatment | Additional efficacy assessments comprised a variety of known scales used for evaluating subjects with celiac disease, including the Gastrointestinal Symptoms Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), Short Form 12 health survey Version 2 (SF12v2), Celiac Disease Quality of Life (CeD-QoL) scale, and the Clinical Global Assessment (CGA). A Gluten-Free Diet Compliance Questionnaire (GFDCQ) and Celiac Dietary Adherence Test (CDAT) were also included to assess compliance with the gluten-free diet. | GSRS - weekly; BSFS - daily; CGA - screening, baseline, Week 12 and follow-up visits; CeD-QoL and SF12v2 - start of placebo run-in, Week 12 and follow-up visits; CD and CFDCQ - follow-up visit. | 

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