Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects

• ClinicalTrials.gov Identifier: NCT00362856
• Recruitment Status: Completed
• First Posted: August 10, 2006
• Last Update Posted: September 12, 2017
• Sponsor: 9 Meters Biopharma, Inc.
• Information provided by (Responsible Party): 9 Meters Biopharma, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Celiac Disease	Drug: larazotide acetate; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized, double-blind, placebo controlled, dose ranging, multicenter
• Masking: Double (Participant, Investigator)
• Masking Description: double-blind
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: September 13, 2006
• Actual Primary Completion Date: March 6, 2007
• Actual Study Completion Date: March 6, 2007

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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

Secondary Outcome Measures :

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Research Site

Scottsdale, Arizona, United States, 85259

United States, California

San Diego, California, United States, 92123

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02215

United States, Minnesota

Research Site

Rochester, Minnesota, United States, 55905

United States, New Jersey

Morristown, New Jersey, United States, 07960

United States, North Dakota

Bismarck, North Dakota, United States, 58501

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19107

Pittsburgh, Pennsylvania, United States, 15241

United States, Virginia

Research Site

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

9 Meters Biopharma, Inc.

More Information

Publications of Results:

Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24.

• Responsible Party: 9 Meters Biopharma, Inc.
• ClinicalTrials.gov Identifier: NCT00362856
• Other Study ID Numbers: CLIN1001-004
• First Posted: August 10, 2006
• Last Update Posted: September 12, 2017
• Last Verified: September 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by 9 Meters Biopharma, Inc.:

larazotide acetate

Additional relevant MeSH terms:

Celiac Disease; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases