Larazotide

Research overview

Key studies

1. Paterson et al., Aliment Pharmacol Ther (2007)

   In-patient, double-blind, randomized, placebo-controlled single-dose safety study with gluten challenge
   Model: Humans (adults with celiac disease)

   No increase in adverse events versus placebo; after gluten exposure, intestinal permeability rose 70% in the placebo group but not in the AT-1001 group, and gastrointestinal symptoms were more frequent with placebo ^4.

2. Leffler et al., Am J Gastroenterol (2012)

   Dose-ranging, randomized, double-blind, placebo-controlled, 14 days with or without gluten challenge
   Model: Humans (86 adults with diet-controlled celiac disease)

   The lactulose/mannitol ratio difference versus placebo was not significant and was highly variable; some lower doses, but not the highest, appeared to limit gluten-induced symptom worsening ^3.

3. Kelly et al., Aliment Pharmacol Ther (2013)

   Exploratory randomized, double-blind, placebo-controlled gluten-challenge study, 6 weeks
   Model: Humans (184 adults with celiac disease)

   No significant difference in lactulose-to-mannitol ratio; the lowest dose limited gluten-induced symptoms and all doses showed lower anti-tTG IgA rise versus placebo; adverse event rates were similar to placebo ^2.

4. Leffler et al., Gastroenterology (NCT01396213) (2015)

   Multicenter, randomized, double-blind, placebo-controlled, 12 weeks of treatment
   Model: Humans (342 adults with celiac disease and persistent symptoms on a gluten-free diet)

   The primary symptom endpoint (CeD-GSRS) was met with the lowest dose only; the two higher doses did not differ from placebo; adverse events were comparable with placebo ^1.

5. Gopalakrishnan et al., Peptides (2012)

   Cell-culture and transgenic mouse experiments
   Model: Cells (Caco-2, IEC6) and animals (HLA-HCD4/DQ8 mice)

   Larazotide inhibited tight-junction opening caused by gliadin, AT-1002 and cytokines, and preserved tight-junction structure in sensitized mice ^5.

6. Yonker et al., Sci Transl Med (2025)

   Phase 2a randomized, double-blind, placebo-controlled, 3 weeks of adjuvant treatment with 24-week follow-up
   Model: Humans (12 children with post-COVID MIS-C, median age 5.7 years)

   No larazotide-related adverse events were reported; treated children showed faster resolution of gastrointestinal symptoms and faster spike-antigen clearance ^8.

Doses used in published trials

What investigators administered in the cited studies, recorded as a fact about those studies. Not a protocol and not a recommendation.

• In the phase 2b trial NCT01396213 (342 adults), participants received larazotide acetate 0.5, 1 or 2 mg capsules three times daily or placebo for 12 weeks, after a 4-week placebo run-in and before a 4-week placebo run-out ^1,11.
• In the phase 3 trial NCT03569007 (307 enrolled; terminated by sponsor), arms were larazotide 0.25 mg or 0.50 mg capsules three times daily, or matching placebo ^10.
• In the gluten-challenge trial by Kelly et al. (184 patients), arms were 1, 4 or 8 mg three times daily or placebo, with 2.7 g of gluten daily for 6 weeks ^2.
• In the long COVID phase 2a trial NCT05747534, participants received 250 or 500 micrograms orally four times daily for 21 days (by body weight below or at least 25.0 kg), or placebo ^12.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

• Headache
  Among the most common adverse events (rates not given in the abstract)
  86 adults with celiac disease, 14-day trial ³ · No serious adverse events were observed
• Urinary tract infection
  Among the most common adverse events (rates not given in the abstract)
  86 adults with celiac disease, 14-day trial ³ · No serious adverse events were observed
• Overall adverse events
  Similar to placebo
  184 adults with celiac disease undergoing 6-week gluten challenge; 342 adults over 12 weeks ² · Not graded in the abstracts

What is not known: Whether larazotide changes intestinal permeability in humans has not been shown; trials found no significant difference in the lactulose-to-mannitol ratio ^2,3,7. Phase 3 efficacy results were not identified in the registry, which records the trial as terminated by the sponsor ^10. Results of the completed long COVID phase 2a trial were not posted as of 2026-10-24 ^12. Long-term safety, human pharmacokinetics and half-life were not reported in the sources reviewed. The proposed link to zonulin has been questioned ^9.

Regulatory status

Status

Investigational; not FDA-approved for any use as of 2026-10-24. The phase 3 celiac disease trial (NCT03569007) is recorded as terminated by the sponsor, and phase 2a trials in long COVID and MIS-C have been run by Massachusetts General Hospital ^10,12,13.

United States (FDA)

No FDA approval was identified as of 2026-10-24; the phase 3 trial NCT03569007 is recorded as terminated by the sponsor (last update July 2022) ^10.

Sport (WADA)

Larazotide is not named on the WADA 2026 Prohibited List; S0 prohibits at all times any pharmacological substance not addressed elsewhere on the List with no current governmental approval for human therapeutic use, such as drugs under clinical development ^14.

Status varies by country and changes over time. How we describe regulatory status.

References

1. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial Gastroenterology. 2015
2. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study Aliment Pharmacol Ther. 2013
3. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge Am J Gastroenterol. 2012
4. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study Aliment Pharmacol Ther. 2007
5. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo Peptides. 2012
6. Larazotide acetate promotes tight junction assembly in epithelial cells Peptides. 2012
7. Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials Clin Res Hepatol Gastroenterol. 2022
8. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide Sci Transl Med. 2025
9. Lack of relationship of AT1001 to zonulin and prehaptoglobin-2: clinical implications Gut. 2021
10. ClinicalTrials.gov record NCT03569007: Phase 3 study of larazotide acetate for persistent symptoms in celiac disease on a gluten-free diet (terminated) ClinicalTrials.gov. 2026
11. ClinicalTrials.gov record NCT01396213: Phase 2 dose-ranging study of larazotide acetate in celiac disease ClinicalTrials.gov. 2026
12. ClinicalTrials.gov record NCT05747534: Phase 2a study of larazotide (AT1001) for long COVID in children and adults ClinicalTrials.gov. 2026
13. ClinicalTrials.gov record NCT05022303: Phase 2a study of AT1001 for COVID-19 related MIS-C (terminated) ClinicalTrials.gov. 2026
14. World Anti-Doping Agency Prohibited List 2026 (online version) WADA. 2026
15. PubChem compound record for larazotide PubChem. 2026