Randomized, Double-Blind, Placebo-Controlled Study of Larazotide Acetate in Subjects With Active Celiac Disease

Study Overview
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Brief Summary
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This study was conducted to assess the safety and efficacy of larazotide acetate versus placebo in inducing remission in subjects with active celiac disease.

Detailed Description
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This was an outpatient, randomized, parallel- group, double-blind, multicenter, 8-week study with three treatment arms: larazotide acetate 4 mg TID, larazotide acetate 8 mg TID and placebo TID in subjects with celiac disease. The primary objective was to assess the efficacy of larazotide acetate versus placebo in inducing remission in subjects with active celiac disease, as defined by an improvement in the Villous Height to Crypt Depth (Vh:Cd) ratio, obtained by duodeno-jejunal biopsy. Secondary objectives included assessment of the safety and tolerability of larazotide acetate, to prospectively validate the components of a composite weighted index of celiac disease activity (celiac disease Activity Rating Score, CeDARS), individually and as a whole, to To compare the CeDARS against the Clinician Global Assessment of disease (CGA), Psychological Well Being Index and the Short Form 12 version 2 (SF-12 v2) health survey and to assess the effects of larazotide acetate on inflammatory markers in subjects with active celiac disease.

Official Title
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A Phase IIb, Randomized, Double-Blind, Placebo Controlled Study for the Treatment of Active Celiac Disease With Larazotide Acetate (AT-1001)

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 celiac disease (as demonstrated by duodenal/jejunal biopsy or by capsule endoscopy plus positive anti-tTG) Marsh score ≥ II at screening Positive serum anti-tTG antibodies as determined by screening serology Willing to comply with a gluten-free diet for the duration of the study Exclusion Criteria: Has refractory Celiac Disease or severe complications of celiac disease (eg, EATL-, ulcerative jejunitis, perforation, etc.) Has chronic active GI disease other than Celiac Disease Has diabetes (Type 1 or Type 2) or other autoimmune disease that might interfere with the conduct of the study Has hemoglobin value below 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, parallel- group, double-blind, multicenter
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Larazotide acetate 4 mg<br>larazotide acetate capsules 4 mg TID | Drug: larazotide acetate<br>* gelatin capsule<br>* Other names: INN-202;|
| Experimental: Larazotide acetate 8 mg<br>Larazotide acetate capsules 8 mg TID | Drug: larazotide acetate<br>* gelatin capsule<br>* Other names: INN-202;|
| Placebo Comparator: Placebo<br>Placebo capsules | 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 in inducing remission in subjects with active celiac disease | Remission was defined as an improvement in the Villous Height to Crypt Depth (Vh:Cd) ratio obtained by duodeno-jejunal biopsy. | duodeno-jejunal biopsies were performed at Baseline and Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of larazotide acetate | Safety endpoints assessed in this study were adverse events, vital signs, physical examination results, clinical laboratory test results and ECG results. Plasma larazotide acetate and metabolites, as well as potential serum antibodies against larazotide acetate, were also determined. | Up to 8 weeks | 
| To prospectively validate the components of a composite weighted index of Celiac Disease activity (Celiac Disease Activity Rating Score, CeDARS), individually and as a whole. | Candidate components of the CeDARS Index measured in this study were GSRS, anti-tTG antibodies, LAMA ratio, Hb, ferritin, body weight, triceps skin fold thickness, BMI, urinary nitrates | Up to 8 weeks | 
| To compare the CeDARS against the Clinician Global Assessment of disease (CGA), Psychological Well Being Index (PWBI) and the Short Form 12 version 2 (SF-12v2) health survey. | The CGA was completed by the PI or designee; the PWBI and SF-12v2 were completed by the subject. | CGA, PWBI and SF-12v2 were collected at Visits 2, 3 and 4. | 
| To assess the effects of larazotide acetate on inflammatory markers in subjects with active celiac disease subjects | Blood for serum was drawn for potential future determination of inflammatory mediators that might be involved in the response of Celiac Disease to larazotide acetate, such as cytokines (e.g. TNF-α,IFN-γ) or the putative permeability factor zonulin. | Blood draws occurred at Visits 1, 2, 3, 4 and 5. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, Active, Celiac, Remission, Induction