Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects

September 11, 2017 updated by: 9 Meters Biopharma, Inc.

A Phase 2a, 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 Gluten Challenge.

This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

CLIN1001-004 was a randomized, double-blind, placebo controlled, dose-ranging, 7-arm, multicenter study with a gluten challenge. The objects were multiple dose safety and tolerance; efficacy (intestinal permeability [change in urinary LAMA ratio] and disease signs and symptoms) following gluten challenge.

Following a 21-day screening period, subjects were randomized to one of seven treatments groups: four groups received larazotide acetate (0.25 mg, 1 mg, 4 mg or 8 mg TID) along with an 800 mg gluten challenge, one group received placebo with an 800 mg gluten challenge, a safety control arm received the highest dose of larazotide acetate (8 mg TID) and gluten placebo and the last group received drug placebo and gluten placebo. The gluten challenge was administered as capsules (800 mg TID) with each main meal for a total of 2.4 g daily. Drug or drug placebo was administered TID 15 minutes prior to each main meal. Subjects received their assigned treatments for two weeks (Day 0 through Day 14) and came to clinic for a follow-up visit one week later (Day 21). Subjects remained on their gluten-free diet for the duration of the study.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Research Site
    • California
      • San Diego, California, United States, 92123
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Site
    • New Jersey
      • Morristown, New Jersey, United States, 07960
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15241
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have been diagnosed with celiac disease by biopsy for ≥ 6 months.
  • Have a Anti-Tissue Transglutaminase (tTG) ≤ 10 EU as measured by serology.
  • Must be on a gluten-free diet for at least the past 6 months.

Exclusion Criteria:

  • Have any chronic active GI disease other than celiac disease (e.g., IBS, Crohn's, Colitis).
  • Have diabetes (Type 1 or Type 2).
  • Chronically consumes non-steroidal anti-inflammatory agents ("NSAIDs") or takes proton-pump inhibitors.
  • Consuming oral corticosteroids or immune suppressants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo + Gluten
placebo TID + gluten 800 mg TID administered orally in capsules
Drug: Placebo
capsule
Placebo Comparator: Placebo + Gluten placebo
placebo TID + gluten placebo TID administered orally in capsules
Drug: Placebo
capsule
Other: Larazotide acetate 8 mg + Gluten placebo
Safety Control Arm. Larazotide acetate 8 mg TID + gluten placebo TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 0.25 mg + Gluten
Larazotide acetate 0.25 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 1 mg + Gluten
Larazotide acetate 1 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 4 mg + Gluten
Larazotide acetate 4 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 8 mg + Gluten
Larazotide acetate 8 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
Time Frame: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).
Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG
Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21).
To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge
Time Frame: On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies.
The primary efficacy outcome was the Day 0-to-Day 14 change in urinary LAMA ratio ( a measure of intestinal permeability) as a response to gluten
On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in daily and weekly reported health outcomes
Time Frame: Symptom diary - daily; PGWBI - weekly; GSRS - weekly
Health outcomes were assessed using a daily symptom diary; a weekly PGWBI and a weekly GSRS
Symptom diary - daily; PGWBI - weekly; GSRS - weekly
Changes in urinary LAMA ratios between Day 0 to Day 7
Time Frame: See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14
Time Frame: See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14
Time Frame: See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
See Primary Outcome Measure No. 2
Change in urinary nitrite / nitrate levels from Day 0 to Day 14
Time Frame: Day 0 and Day 14
Nitrite/nitrate levels were assessed for correlation to the measures of intestinal permeability
Day 0 and Day 14
Change in anti-tTG levels from Screening to Day 21
Time Frame: Screening and Day 21
Changes between screening and Day 21 anti-tTG levels were assessed for correlation to the measures of intestinal permeability
Screening and Day 21
Change in cell markers and cytokines from PBMCs
Time Frame: Days 0, 7, 14 and 21
Serum cytokine and cell surface marker determinations were assessed for correlation to the measures of intestinal permeability
Days 0, 7, 14 and 21
Changes in zonulin level
Time Frame: Days 0, 7, 14 and 21
Serum zonulin levels were assessed for correlation to the measures of intestinal permeability
Days 0, 7, 14 and 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

9 Meters Biopharma, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 13, 2006

Primary Completion (Actual)

March 6, 2007

Study Completion (Actual)

March 6, 2007

Study Registration Dates

First Submitted

August 8, 2006

First Submitted That Met QC Criteria

August 8, 2006

First Posted (Estimate)

August 10, 2006

Study Record Updates

Last Update Posted (Actual)

September 12, 2017

Last Update Submitted That Met QC Criteria

September 11, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIN1001-004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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