Safety Study of AT1001 to Treat Celiac Disease.

Condition(s) targeted: Celiac Disease

Intervention: AT-1001 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Alba Therapeutics

Official(s) and/or principal investigator(s):
Blake Paterson, MD, Study Chair, Affiliation: Alba Therapeutics

To demonstrate the safety and tolerance of single, oral doses of AT-1001 in celiac disease subjects that are gluten-free diets and in remission.

Official title: A Phase Ib, Randomized, Double-Blind, Placebo Controlled Study to Determine the Safety, Tolerance, Pharmacokinetic and Pharmacodynamic Effects of Single Doses of AT-1001 in Celiac Disease Subjects.

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety Study

Primary outcome:

To demonstrate the safety and tolerance of single, oral doses of AT-1001 in celiac disease subjects that are gluten-free and in remission

To determine whether quantifiable AT-1001 concentrations are present in plasma following single oral doses and to characterize the pharmacokinetic behavior of AT-1001 in celiac disease subjects that are gluten-free and in remission

To evaluate the effects of single doses of AT-1001 on intestinal permeability ratios and zonulin levels following single, oral challenge doses of gluten (2.5 gm) by utilizing urinary lactulose and mannitol, and serum zonulin concentrations as biomarkers.

Secondary outcome:

Self-reported measures of GI discomfort

Pharmacokinetic Measures

Pharmacodynamic Measures

Detailed description: One (1) cohort of 24 (2: 1 drug: placebo) subjects will receive single oral doses of either AT-1001 or matching placebo. Subjects will complete screening and thereafter be admitted to the clinic prior to treatment. On Day 1 AT-1001 or matching placebo will be administered followed by a baseline intestinal permeability test. Intestinal permeability will be measured by administration of an oral sucrose, lactulose and mannitol solution followed by an 8-hour urine collection. Day 2 subjects will be given AT-1001 or matching placebo followed by a gluten challenge and have the intestinal permeability test repeated. Day 3 subjects will be administered AT-1001 or matching placebo followed by a post gluten challenge intestinal permeability test. Serial blood samples will be collected for pharmacokinetic determinations at baseline, 2, and 3 hours post administration of AT-1001 or matching placebo, for zonulin determinations at baseline (prior to first dose) and at 3 hours post dose, and for cytokine determination at baseline, 3 hours post dose (Days 2 and 3 only) and Day 7. Sucrose, lactulose, mannitol, zonulin and AT-1001 concentrations will be determined by validated analytical methods.

Subjects will be evaluated at screening (medical history, physical examination, vital signs, clinical laboratory testing, and 12-lead electrocardiogram). Vital signs and clinical laboratory testing will be conducted pre-dose and vital signs, clinical laboratory testing and EKG will be monitored post dose. Adverse event reports will be monitored throughout the study. At the end of the study a physical exam and clinical laboratory testing will be performed.

Minimum age: 18 Years. Maximum age: 59 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subject must have been diagnosed with celiac disease by biopsy for ≥ 6 months

(attending physician confirmation will be accepted in lieu of a biopsy report).

- Subject must be on a gluten-free diet for at least the past 6 months.

Exclusion Criteria:

- Subject has Anti-Tissue Transglutaminase (tTG) > 10 EU as measured by serology

- Subject intermittently consumes clinically significant quantities of non-steroidal

anti-inflammatory agents (“NSAIDs”) and proton-pump inhibitors, within the last 3 days prior to the treatment visit.

Parexel, Baltimore, Maryland 21225, United States

Starting date: January 2006
Ending date: February 2006
Last updated: October 10, 2006