Larazotide

Larazotide at a Glance

Larazotide is an octapeptide designed to act only inside the gut — it is not absorbed, which is unusual and deliberate. It blocks zonulin, the signal that loosens the tight junctions between intestinal cells, and was developed to keep the barrier closed in celiac disease so gluten fragments could not cross. It progressed further than almost any peptide in this category, reaching phase 3, where it did not meet its primary endpoint. It is investigational and unapproved.

History & Development

Larazotide got further than any other drug for celiac disease, and then stopped - not because it did not work, but because the trial could not prove that it did at any feasible size.

First described	Entered clinical trials in the mid-2000s, as AT-1001 4Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →
Discovered / synthesised by	Not established in the sources consulted for this section
Institution	Developed by Alba Therapeutics, later 9 Meters Biopharma 4,19Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →Reference 19Beyond Celiac · 2022Phase 3 study of larazotide acetate to treat celiac disease discontinued. https://www.beyondceliac.org/research-news/phase-3-study-discontinued/View study →
Origin	De-novo synthetic octapeptide, designed as a zonulin antagonist
Key patent	Not established in the sources consulted for this section
Assignee	9 Meters Biopharma
Development status	Discontinued at Phase 3 - CeDLara trial stopped 21 June 2022 after interim analysis 19Reference 19Beyond Celiac · 2022Phase 3 study of larazotide acetate to treat celiac disease discontinued. https://www.beyondceliac.org/research-news/phase-3-study-discontinued/View study →

Discovery

The idea behind larazotide is that celiac disease begins with a barrier failure. Zonulin regulates the tight junctions between intestinal epithelial cells; when it signals, the junctions loosen and molecules that should stay in the gut lumen - including gluten peptides - can cross into the tissue beneath, where the immune reaction happens.

Larazotide is an octapeptide designed to block that signal and keep the junctions closed. Two design choices define it: it is oral, and it is gut-restricted - deliberately not absorbed, so it acts only on the epithelium it passes over and has essentially no systemic exposure. That is unusual and it is a genuine safety advantage.

It entered clinical trials as AT-1001 more than fifteen years ago, making it the first drug candidate for celiac disease to reach human testing at all ^{4Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →}. A Phase 2 study in 342 adults already on a gluten-free diet found that the 0.5 mg dose significantly reduced persistent symptoms - and notably, the lowest dose outperformed higher ones ^{4Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →}.

Development & ownership

Development began at Alba Therapeutics and later moved to 9 Meters Biopharma, which took the compound into Phase 3 in 2020 - the first celiac drug ever to get there ^{19Reference 19Beyond Celiac · 2022Phase 3 study of larazotide acetate to treat celiac disease discontinued. https://www.beyondceliac.org/research-news/phase-3-study-discontinued/View study →}.

The CeDLara trial did not meet its primary endpoint. On 21 June 2022, 9 Meters announced discontinuation, and the stated reason is worth quoting precisely: an interim analysis found that the sample size needed to demonstrate a significant difference from placebo was too large to support continuing the trial ^{19Reference 19Beyond Celiac · 2022Phase 3 study of larazotide acetate to treat celiac disease discontinued. https://www.beyondceliac.org/research-news/phase-3-study-discontinued/View study →}. That is not the same as a drug that does nothing - it is a drug whose effect, if real, is too small to prove at a practical trial size.

How it reached the market

It did not. Larazotide has never been approved anywhere and is not sold as a supplement or research chemical in any meaningful volume - unlike most compounds here, its story ends with the programme rather than continuing into grey-market supply. Celiac disease still has no approved drug treatment; a gluten-free diet remains the only management.

What It's Used For

Larazotide (larazotide acetate; AT-1001, INN-202) is a synthetic eight-amino-acid peptide — Gly-Gly-Val-Leu-Val-Gln-Pro-Gly — whose sequence derives from a fragment of the Vibrio cholerae zonula occludens toxin (ZOT). It acts as a zonulin antagonist: it blocks the signaling that pulls intestinal tight junctions open, reducing the paracellular (“leaky gut”) permeability that lets gliadin peptides and other macromolecules cross the epithelium. The route story is the inverse of almost every other peptide here. Most research peptides must be injected because the gut would destroy them; larazotide is taken orally precisely because it is not absorbed — it is designed to work in the lumen, on the apical face of the epithelium, and reaches negligible plasma concentrations. Non-absorption is the feature, not a limitation, and it reframes the entire safety and dosing picture below. Larazotide also has more human data behind it than most compounds in this category — several completed randomized controlled trials in celiac disease, including a positive phase 2b — but the decisive fact is what happened next: the confirmatory phase 3 celiac trial (CeDLara, NCT03569007) was stopped in June 2022 after an interim analysis found continuation unjustifiable, and larazotide has never been approved by any regulator, for any indication, anywhere.

Evidence by IndicationStrength of support · Beta

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric. Each application links down to its write-up.

01Celiac disease (adjunct to gluten-free diet)Promising58%Multiple human RCTs + a positive phase 2b + meta-analysis — but the phase 3 was stopped for futility and it was never approved.

02Post-COVID MIS-C in childrenShaky40%One phase 2a RCT that enrolled 12 children before terminating early, plus a 4-patient case series. One group.

03Non-celiac gut-barrier protectionShaky28%Porcine ex-vivo and rodent models (ischemia, colitis, pancreatitis, liver failure, NAFLD). No human data.

04Skin barrier / atopic dermatitisShaky15%A single in-vitro human keratinocyte study (PAR2 antagonism). No animal or human data; skin penetration unknown.

Mechanisms

Pharmacokinetics

Larazotide is given orally and is gut-restricted — this is the single most decision-relevant fact on the page. It is designed to act on the luminal side of the intestinal epithelium and reaches negligible systemic concentrations, which is exactly why an oral route works for a peptide that would otherwise be irrelevant by mouth. The corollary matters just as much: there is no meaningful systemic exposure to speak of, so plasma half-life, clearance, and volume of distribution are not the operative pharmacology. Local luminal concentration, site of release, and stability in the gut are.

As an octapeptide it is degraded in the intestine by brush-border aminopeptidases into fragments. Not all fragments are inert — one, lacking both N-terminal glycines, can antagonize the parent peptide, which is part of the rationale for delayed-release formulations and D-amino-acid analogues ^{16Reference 16Slifer ZM et al. · 2021ReviewLarazotide acetate: a pharmacological peptide approach to tight junction regulation — reviewView study →}. A delayed-release formulation designed to deliver drug to the duodenum and proximal jejunum — the site of celiac injury — was characterized in a porcine model, giving peak luminal concentrations in the low-micromolar range roughly an hour after dosing ^{15Reference 15Enomoto H et al. · 2021AnimalIn vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model — animal (porcine, formulation PK)View study →}. Clinically it was dosed before meals: three times daily in the celiac trials, four times daily in the MIS-C and Long COVID trials. No verified human bioavailability or half-life figure exists, and none is expected to be informative for a compound whose intended pharmacology is entirely local.

Clinical & regulatory status

Larazotide is an unapproved investigational drug. It has never been approved by the FDA, EMA, TGA, PMDA, or any other regulator, for any indication, and it is not a dietary supplement or a prescription medicine.

The development history runs Alba Therapeutics (the originator, which licensed the intellectual property onward) → Innovate Biopharmaceuticals → 9 Meters Biopharma, which held it as its lead celiac program. After the phase 3 CeDLara termination in June 2022, 9 Meters deprioritized larazotide and pivoted to other assets; the company ceased operations and filed for Chapter 7 bankruptcy in July 2023. Where the larazotide rights sit today is not clearly documented in public sources — treat current ownership as unknown, not as “abandoned.”

Registered clinical activity has since shifted entirely to investigator-sponsored work at Massachusetts General Hospital: the phase 2a MIS-C trial (NCT05022303, terminated early at n=12, results published 2025) and a phase 2a Long COVID trial (NCT05747534, n=107, active/not recruiting, estimated completion September 2026, no results posted).

A naming trap worth knowing: the code “AT1001” also designates migalastat (Galafold), Amicus Therapeutics’ approved Fabry-disease drug — a completely unrelated small molecule. The many Fabry “AT1001” trials on ClinicalTrials.gov are not larazotide, and migalastat’s approvals say nothing about larazotide’s status. Vendor copy occasionally conflates the two.

There are no approved indications and no registered trials of any kind supporting the generic “leaky gut” and gut-repair uses under which larazotide is marketed on the research-chemical market.

Last checked: July 2026.

Sourcing, Route & Legal Status

Regulatory status. Larazotide is an investigational drug that has never been approved anywhere, by any regulator, for any indication. It is not a dietary supplement, not a prescription medicine, and not a compound with a legal consumer market. Its most advanced test — the phase 3 CeDLara celiac trial (NCT03569007) — was discontinued by the sponsor in June 2022 following an interim analysis that found the trial could not realistically demonstrate a significant difference from placebo; the registry lists it simply as “Terminated / Trial terminated by Sponsor,” and the futility framing comes from 9 Meters’ own June 2022 announcement, not from the registry record. Anything sold to consumers as “larazotide” is therefore an unapproved research chemical, typically labeled “for research use only / not for human consumption.” It is not a scheduled or controlled substance, but “not scheduled” is not “approved” — marketing it for human use is unlawful in most Western jurisdictions.

How it’s supplied & administered — the route is the story. Larazotide is a small synthetic octapeptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) supplied as lyophilized powder or in oral capsule/solution form. Unlike essentially every other research peptide, the intended route is oral — and it works orally because the peptide is gut-restricted and barely absorbed, acting locally in the intestinal lumen rather than entering the bloodstream. There is no reconstitution for injection, no injection-site risk, and no sterile-technique burden — the entire injection-safety discussion that dominates other peptide pages simply does not apply here. What replaces it is formulation: because activity depends on delivering intact peptide to the duodenum and proximal jejunum, release characteristics matter far more than they would for an injected compound, and a generic capsule of raw powder is not equivalent to the delayed-release formulation used in trials. In trials it was taken before meals — three times daily for celiac, four times daily for MIS-C.

Sourcing reality (this is a safety issue, not a footnote). Larazotide sold outside a clinical trial comes from unregulated vendors with no manufacturing oversight. Identity, correct sequence, purity, degradation state, and absence of contaminants cannot be assumed and cannot be assessed by eye; a peptide this short is also cheap to counterfeit or under-dose. Third-party certificates of analysis — mass-spec identity and HPLC purity — are the minimum a buyer would need to know what they actually have, and even a clean COA does not make an unapproved drug safe or effective for an indication that failed in trials. No vendors are recommended or linked here.

Safety

Larazotide barely leaves the gut, and its trial record is correspondingly quiet — adverse events tracked placebo, and the phase 3 was stopped for futility rather than harm. The real exposure is to the product, not the pharmacology: an unapproved drug bought from unregulated vendors.

Safety at a Glance

✅ Low / no toxicity

• Well tolerated in trials. Adverse-event rates comparable to placebo across the celiac studies, and no drug-related events in the pediatric MIS-C trial.
• The phase 3 trial was stopped for futility, not for harm. The failure was efficacy.
• Contraindicated by default in pregnancy and breastfeeding. Not assessed — see the box below.
• An unapproved investigational drug from unregulated vendors. Identity, purity and degradation state can’t be assessed by eye, and a peptide this short is cheap to counterfeit.
• No long-term safety data. Trials ran weeks to months, and chronically manipulating the intestinal barrier outside a monitored trial is unstudied.
• Interactions are unknown, not none. Nothing has been tested, in either direction.

Full Safety & Interactions Detail

Overall posture. Larazotide’s safety record in trials is genuinely reassuring as far as it goes, which is further than most compounds in this category. Across phase 1, phase 2, and the phase 2b celiac studies it was generally well tolerated, with adverse-event rates comparable to placebo at doses from roughly 0.25 mg to 8 mg ^{1,2,3,4Reference 1Paterson BM et al. · 2007RCTThe safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study — human (RCT, phase 1)View study →Reference 2Leffler DA et al. · 2012RCTA randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge — human (RCT)View study →Reference 3Kelly CP et al. · 2013RCTLarazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study — human (RCT)View study →Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →}, and the 2022 meta-analysis found no excess of adverse events — it actually reported less gluten-related diarrhea than placebo during gluten challenge ^{5Reference 5Hoilat GJ et al. · 2022Meta-analysisLarazotide acetate for treatment of celiac disease: a systematic review and meta-analysis of randomized controlled trials — human (meta-analysis, 4 RCTs)View study →}. In the pediatric MIS-C phase 2a trial and case series, oral larazotide at 10 µg/kg four times daily produced no drug-related adverse events ^{6,7Reference 6Yonker LM et al. · 2025RCTViral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide — human (RCT, phase 2a, n=12)View study →Reference 7Yonker LM et al. · 2022Case reportZonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: a case series — human (case series, n=4)View study →}. This is consistent with the pharmacology: a compound that is not meaningfully absorbed has little opportunity to cause systemic toxicity. Note also that the phase 3 trial was stopped for futility, not for harm — the failure was efficacy, not safety.

What that does and does not establish. Trials ran weeks to months (celiac studies up to roughly 24 weeks; MIS-C for 21 days plus follow-up). There is no long-term human safety data, no data in unsupervized use, and no data at all on unregulated research-market product. “Low adverse-event signal in short trials” is not “safe for chronic self-administration.”

Dose-limiting and route-specific risks. No distinctive dose-limiting toxicity emerged in the doses tested; the 0.5 mg dose was both the effective and the well-tolerated one, and higher doses were less effective rather than more toxic. Because the route is oral, the dominant practical risks are product risks rather than drug risks: misidentified or impure vendor material, degradation, and contamination. There is a theoretical mechanistic caution worth naming as such — a compound that deliberately modulates intestinal tight-junction permeability is altering a barrier that regulates what enters the body, and the long-term consequences of chronically manipulating that barrier outside a monitored trial have not been studied.

Interactions. Not formally assessed. In principle, minimal systemic absorption makes classical pharmacokinetic drug–drug interactions unlikely, and there is a plausible argument that altering intestinal permeability could affect absorption of co-administered oral drugs — but neither has been tested. Treat interactions as unknown, not as “none.”

Who should avoid it. Anyone pregnant, breastfeeding, or trying to conceive; children outside a supervised trial; and anyone unwilling to accept an unapproved investigational drug of unverified identity and purity, taken for an indication where the confirmatory trial failed.

Scope disclosure (honesty, not a claim):

• Human data? Yes, unusually — multiple celiac RCTs including a positive phase 2b, plus a small pediatric MIS-C phase 2a RCT. But the confirmatory phase 3 was stopped for futility, and there is no approved use.
• Interactions assessed? No. Low systemic absorption makes pharmacokinetic interactions unlikely in principle; nothing has been tested.
• Pregnancy/lactation assessed? No — no human or animal reproductive data located.
• Long-term safety established? No. Trials ran weeks to months; there is no long-term or research-market safety data.

Never imply safety from silence. Where larazotide has not been studied — interactions, pregnancy, chronic use, and unregulated product quality — the correct statement is “not assessed,” not “safe.”

Pregnancy & Lactation

? Not established in pregnancy? Not established in lactation

Not assessed / not established. There are no human pregnancy or lactation data for larazotide, and no reproductive-toxicity data in the accessible literature. Minimal systemic absorption is a plausible reason to expect low fetal exposure, but that is an inference from pharmacology, not a finding. Treat as contraindicated by default in pregnancy and breastfeeding.

Dosage

There is no established human dose for larazotide, and none is recommended here. It is an unapproved investigational drug with no approved indication anywhere, and every figure below is data reported for context, not a personal recommendation.

In the celiac program, larazotide was given orally before meals, three times daily, across a tested range of roughly 0.25 mg to 8 mg per dose. The 0.5 mg dose was the one that met the primary endpoint in the phase 2b trial, and — importantly — higher doses performed no better than placebo, a non-monotonic dose–response attributed to peptide self-aggregation ^{4Reference 4Leffler DA et al. · 2015RCTLarazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b)View study →}. More is explicitly not better here. In the pediatric MIS-C trials the dose was weight-based: 10 µg/kg four times daily, capped at 500 µg per dose, for 21 days ^{6,7Reference 6Yonker LM et al. · 2025RCTViral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide — human (RCT, phase 2a, n=12)View study →Reference 7Yonker LM et al. · 2022Case reportZonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: a case series — human (case series, n=4)View study →}.

Two caveats do real work. First, the trial material was a delayed-release formulation engineered to release in the duodenum and proximal jejunum ^{15Reference 15Enomoto H et al. · 2021AnimalIn vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model — animal (porcine, formulation PK)View study →}; raw powder in a generic capsule is not pharmacologically equivalent, so a “0.5 mg dose” of vendor material is not the trial dose in any meaningful sense. Second, the dose that produced the phase 2b signal is the same dose that failed to confirm in phase 3 — reproducing the number does not reproduce a demonstrated benefit. This entry is informational only.

References

1. Paterson BM, Lammers KM, Arrieta MC, Fasano A, Meddings JB. (2007). The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study — human (RCT, phase 1). Alimentary Pharmacology & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/17697209/
2. Leffler DA, Kelly CP, Abdallah HZ, et al. (2012). A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge — human (RCT). American Journal of Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/22825365/
3. Kelly CP, Green PH, Murray JA, et al. (2013). Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study — human (RCT). Alimentary Pharmacology & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/23163616/
4. Leffler DA, Kelly CP, Green PH, et al. (2015). Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial — human (RCT, phase 2b). Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/25683116/
5. Hoilat GJ, Altowairqi AK, Ayas MF, et al. (2022). Larazotide acetate for treatment of celiac disease: a systematic review and meta-analysis of randomized controlled trials — human (meta-analysis, 4 RCTs). Clinics and Research in Hepatology and Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/34339872/
6. Yonker LM, Kane AS, Swank Z, et al. (2025). Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide — human (RCT, phase 2a, n=12). Science Translational Medicine. https://pubmed.ncbi.nlm.nih.gov/40737433/
7. Yonker LM, Swank Z, Gilboa T, et al. (2022). Zonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: a case series — human (case series, n=4). Critical Care Explorations. https://pubmed.ncbi.nlm.nih.gov/35211683/
8. Slifer ZM, Krishnan BR, Madan J, Blikslager AT. (2021). Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions — ex vivo (porcine). PLoS One. https://pubmed.ncbi.nlm.nih.gov/33886649/
9. Caliskan AR, Gul M, Yilmaz I, et al. (2021). Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats — animal (rat). Human & Experimental Toxicology. https://pubmed.ncbi.nlm.nih.gov/34791921/
10. Karahan D, Harputluoglu MMM, Gul M, et al. (2024). Ameliorative effects of larazotide acetate on intestinal permeability and bacterial translocation in acute pancreatitis model in rats — animal (rat). Digestive Diseases and Sciences. https://pubmed.ncbi.nlm.nih.gov/38441784/
11. Yu F, et al. (2025). Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment — animal (mouse, DSS colitis) / in vitro. Journal of Controlled Release. https://pubmed.ncbi.nlm.nih.gov/40915363/
12. Kim J, et al. (2025). Larazotide acetate protects the intestinal mucosal barrier from anoxia/reoxygenation injury via various cellular mechanisms — in vitro / animal. Biomedicines. https://pubmed.ncbi.nlm.nih.gov/41153766/
13. Huang YC, et al. (2026). Preventive effects of larazotide acetate (AT-1001) on non-alcoholic fatty liver diseases (NAFLD) in a mouse model — animal (mouse). Pediatrics and Neonatology. https://pubmed.ncbi.nlm.nih.gov/40562584/
14. Glinka DM, et al. (2025). The PAR2 antagonist larazotide can mitigate acute histamine-stimulated epithelial barrier disruption in keratinocytes: a potential adjunct treatment for atopic dermatitis — in vitro (human keratinocytes). JID Innovations. https://pubmed.ncbi.nlm.nih.gov/40330848/
15. Enomoto H, Yeatts J, Carbajal L, et al. (2021). In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model — animal (porcine, formulation PK). PLoS One. https://pubmed.ncbi.nlm.nih.gov/33844694/
16. Slifer ZM, Krishnan BR, Madan J, Blikslager AT. (2021). Larazotide acetate: a pharmacological peptide approach to tight junction regulation — review. American Journal of Physiology — Gastrointestinal and Liver Physiology. https://pubmed.ncbi.nlm.nih.gov/33881350/
17. Troisi J, Venutolo G, Terracciano C, et al. (2021). The therapeutic use of the zonulin inhibitor AT-1001 (larazotide) for a variety of acute and chronic inflammatory diseases — review. Current Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/33397225/
18. Gopalakrishnan S, Durai M, Kitchens K, et al. (2012). Larazotide acetate regulates epithelial tight junctions in vitro and in vivo — in vitro / animal (mouse). Peptides. https://pubmed.ncbi.nlm.nih.gov/22401908/
19. Beyond Celiac (2022). Phase 3 study of larazotide acetate to treat celiac disease discontinued. https://www.beyondceliac.org/research-news/phase-3-study-discontinued/

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