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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Larazotide acetate 8 mg	larazotide acetate	Larazotide acetate capsules 8 mg TID
Placebo	placebo	Placebo capsules
Larazotide acetate 4 mg	larazotide acetate	larazotide acetate capsules 4 mg TID

Primary Outcome Measures

Name	Time	Method
Assess the efficacy of larazotide acetate in inducing remission in subjects with active celiac disease	duodeno-jejunal biopsies were performed at Baseline and Day 56	Remission was defined as an improvement in the Villous Height to Crypt Depth (Vh:Cd) ratio obtained by duodeno-jejunal biopsy.

Secondary Outcome Measures

Name	Time	Method
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.	Up to 8 weeks	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
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.	CGA, PWBI and SF-12v2 were collected at Visits 2, 3 and 4.	The CGA was completed by the PI or designee; the PWBI and SF-12v2 were completed by the subject.
Assess the safety and tolerability of larazotide acetate	Up to 8 weeks	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.
To assess the effects of larazotide acetate on inflammatory markers in subjects with active celiac disease subjects	Blood draws occurred at Visits 1, 2, 3, 4 and 5.	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".