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

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

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

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Drug: larazotide acetate; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2X8
      • Study Site
  • British Columbia
    • Abbotsford, British Columbia, Canada, V5ZIH2
      • Study Site
    • Kelowna, British Columbia, Canada, V1Y2H4
      • Study Site
  • Ontario
    • Richmond Hill, Ontario, Canada, L4B3PB
      • Study Site
• Spain
  • Barcelona, Spain, 08028
    • Study Site
  • Huesca, Spain, 22004
    • Study Site
  • Leon, Spain, 24005
    • Study Site
  • Madrid, Spain, 28007
    • Study Site
  • Madrid, Spain, 28034
    • Study Site
  • Madrid, Spain, 28040
    • Study Site
  • Reus, Spain, 43201
    • Study Site
  • Valladolid, Spain, 47005
    • Study Site
  • Mallorca
    • Palma, Mallorca, Spain, 07014
      • Study Site
• United States
  • California
    • Orange, California, United States, 92868
      • Study Site
    • San Francisco, California, United States, 94115
      • Study Site
  • Connecticut
    • Torrington, Connecticut, United States, 06790
      • Study Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Study Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Study Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Study Site
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Study Site
    • Silver Spring, Maryland, United States, 20901
      • Study Site
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Study Site
    • Troy, Michigan, United States, 48084
      • Study Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Study Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Study Site
    • Harrisburg, North Carolina, United States, 28075
      • Study Site
  • Ohio
    • Gallipolis, Ohio, United States, 45631
      • Study Site
  • Pennsylvania
    • Paoli, Pennsylvania, United States, 19301
      • Study Site
    • Philadelphia, Pennsylvania, United States, 19014
      • Study Site
    • Pittsburgh, Pennsylvania, United States, 15243
      • Study Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Study Site
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Study Site
  • Texas
    • Houston, Texas, United States, 77030
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsules	Drug: placebo; gelatin capsule
Experimental: Larazotide acetate 4 mg; larazotide acetate capsules 4 mg TID	Drug: larazotide acetate; gelatin capsule; Other Names: AT-1001; INN-202
Experimental: Larazotide acetate 8 mg; Larazotide acetate capsules 8 mg TID	Drug: larazotide acetate; gelatin capsule; Other Names: AT-1001; INN-202

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: 9 Meters Biopharma, Inc.
• Investigators: Study Director: Francisco Leon, MD, Ph.D, Alba Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: February 7, 2008
• First Submitted That Met QC Criteria: February 11, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Treatment; Remission; Induction; Celiac; Active
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: AT1001-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No