Larazotide

Larazotide acetate (AT-1001) is a synthetic peptide drug candidate designed to block zonulin-mediated opening of tight junctions between intestinal cells. It was developed specifically for celiac disease, to reduce the gut-permeability increase and downstream immune symptoms triggered by gluten exposure. It reached Phase 3 human clinical trials but its most recent Phase 3 study was discontinued in 2022 after an interim analysis showed it was unlikely to succeed. It is not an FDA-approved medication.

Research snapshot

Category	Current information
Peptide category	Synthetic zonulin-antagonist octapeptide
Primary research interest	Celiac disease symptom relief as an adjunct to a gluten-free diet
Highest available evidence	Published human clinical trials through Phase 3 (terminated for futility)
Human research available	Yes — Phase 1b/2b gluten-challenge study, Phase 2b dose-ranging trial, and a Phase 3 trial terminated in 2022 after an interim futility analysis
Development status	No active, ongoing pivotal registration trial identified as of the last verified date; sponsor 9 Meters Biopharma discontinued the Phase 3 program
Regulatory status	Not FDA-approved; not approved by any other major regulatory agency
Last reviewed	September 27, 2026

Technical identity

Technical property	Information
Primary name	Larazotide acetate
Alternative names	AT-1001, AT1001
Peptide sequence	Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (linear octapeptide, acetate salt)
Amino-acid length	8 residues
Molecular formula	C32H55N9O10 (free peptide, per PubChem)
Molecular weight	Not independently re-derived for this entry from a single authoritative source
CAS Registry Number	881851-50-9
PubChem CID	9810532
Chemical modifications	Acetate salt form
Peptide class	Zonulin-pathway antagonist, tight-junction modulator
Primary biological target	Zonulin signaling pathway, regulating intestinal epithelial tight-junction permeability
Developer or originator	Originally developed by Alba Therapeutics; most recently advanced by 9 Meters Biopharma
Development status	Phase 3 trial (NCT03569007) terminated 2022 after interim futility analysis; no active pivotal trial identified

What it is

Larazotide acetate is a synthetic octapeptide (sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly, formulated as the acetate salt) originally developed under the name AT-1001 by Alba Therapeutics, and later advanced by Innovate Biopharmaceuticals and its successor, 9 Meters Biopharma. It was designed as a “tight junction regulator”: a molecule intended to counteract zonulin, an endogenous protein signal that, in celiac disease, is released in response to gluten exposure and causes the tight junctions between intestinal epithelial cells to open, increasing intestinal permeability (“leaky gut” in permeability terms) and allowing gluten peptides greater access to the underlying immune system.

Unlike enzyme-based or immune-modulating celiac drug candidates, larazotide does not attempt to break down gluten or suppress the immune response directly. Instead, it targets the junction-opening step, with the therapeutic goal of reducing symptom flares that occur from incidental, unintentional gluten exposure in patients who are otherwise trying to maintain a gluten-free diet — not as a replacement for the gluten-free diet itself.

Larazotide has one of the more extensive clinical trial histories of any peptide discussed on this site, spanning Phase 1 pharmacokinetic and safety studies in healthy volunteers, a Phase 1b and Phase 2b acute gluten-challenge study, a large 342-patient Phase 2 dose-ranging trial, and, ultimately, a Phase 3 trial in patients with persistent symptoms despite a gluten-free diet. That Phase 3 trial (NCT03569007) was terminated in 2022 after an interim analysis indicated the trial was unlikely to meet its primary endpoint, effectively ending the drug’s most advanced late-stage development program as of the last verified update. It has also been explored, separately, in early-phase trials for gut-permeability-related conditions outside celiac disease, including Long COVID and COVID-19-associated multisystem inflammatory syndrome in children, sponsored by Massachusetts General Hospital rather than the drug’s original commercial developer.

How does it work?

Plain-English explanation

Picture the lining of the small intestine as a tightly sealed floor made of individual tiles (cells) glued together at every seam. In celiac disease, gluten exposure triggers release of a signal (zonulin) that loosens those seams, letting gluten fragments and other material leak through more easily and trigger inflammation. Larazotide is designed to work like an extra layer of glue at the seams, counteracting that loosening signal so the barrier stays tighter even when gluten is present.

Technical explanation

Larazotide acetate is proposed to act locally within the gut lumen as a tight-junction regulator, antagonizing zonulin-dependent signaling that leads to disassembly of tight-junction protein complexes (such as those involving claudins, occludin, and ZO-1) between enterocytes. By limiting this junction opening, it is intended to reduce paracellular permeability increases associated with gluten exposure in celiac disease, thereby reducing translocation of immunogenic gluten peptides across the epithelial barrier. It is formulated for oral administration and is intended to act locally in the gut rather than being appreciably systemically absorbed, which is consistent with the pharmacokinetic and safety profile reported from its Phase 1 studies in healthy volunteers.

Potential benefits and research applications

Reducing symptoms from gluten exposure in treated celiac disease

What is being investigated: whether larazotide reduces gastrointestinal symptoms (abdominal pain, bloating, diarrhea) in celiac disease patients who remain symptomatic despite an established gluten-free diet, and whether it blunts the effects of an acute, controlled gluten challenge. How the effect might occur: by limiting zonulin-driven tight-junction opening and the resulting immune activation from gluten exposure. Evidence: registered, published human clinical trials, including a Phase 1b/2b gluten-challenge study and a 342-patient Phase 2 dose-ranging trial. Strength: mixed — some earlier-phase studies reported statistically significant improvement on certain symptom measures, particularly in a gluten-challenge model, but the definitive Phase 3 trial designed to confirm a clinical benefit was stopped early for futility. Limitation: no trial has yet produced a result sufficient to support regulatory approval, and the drug’s efficacy in a normal, real-world persistent-symptom population on a gluten-free diet has not been established.

Gut-barrier support in non-celiac permeability-related conditions

What is being investigated: use of larazotide in conditions proposed to involve intestinal barrier dysfunction outside celiac disease, including post-acute COVID-19 syndrome (“Long COVID”) and pediatric multisystem inflammatory syndrome associated with COVID-19 (MIS-C). How the effect might occur: the same proposed tight-junction-stabilizing mechanism, applied to a different suspected trigger of gut permeability. Evidence: is being investigated in early-phase, investigator-initiated trials (sponsored by Massachusetts General Hospital, not celiac-focused developers). Strength: preliminary; these are exploratory studies, and one related MIS-C trial (NCT05022303) was terminated. Limitation: this application rests on the “leaky gut” hypothesis in these other conditions, which is itself an active and unsettled area of research, not an established mechanism of disease.

What dosage information circulates?

Figures in this section summarize amounts and schedules reported in published research or circulating online. Their inclusion documents what is reported and does not establish that a regimen is verified, safe, effective, or appropriate.

Reported use or research objective	Route reported	Amount reported	Frequency reported	Reported duration	Evidence or source category
Celiac disease, Phase 2b dose-ranging	Oral	0.5, 1, or 2 mg	Three times daily (TID)	12 weeks	Published human clinical trial (NCT01396213, n=342)
Gluten-challenge study, Phase 1b/2b	Oral	Doses in a similar range to the Phase 2b trial	Multiple times daily	Short-term controlled gluten challenge	Published human clinical trial (NCT00889473; PMID 25683116)
Persistent symptom relief, Phase 3 (terminated)	Oral	Not reported to a definitive dose-response result; trial stopped before completion	Not reported to a definitive result	Planned 12 weeks; terminated at interim analysis	Registered but terminated trial (NCT03569007, n=307)
General “research compound” framing	Oral	Largely repeats the 0.5-2 mg trial-dose range	Multiple times daily, per trial pattern	Not established	Community / vendor reported, tracing back to the published trial doses rather than an independent origin

Amounts studied in human research

Larazotide has been studied at multiple oral doses across its trial program. The pivotal Phase 2 dose-ranging trial (NCT01396213, n=342) evaluated three doses — 0.5 mg, 1 mg, and 2 mg — each dosed three times daily (TID), as an adjunct to a gluten-free diet, over a 12-week double-blind treatment period. Earlier Phase 1b/2b gluten-challenge work (NCT00889473) tested larazotide at doses in a similar range during a controlled, short-term gluten challenge rather than everyday dietary exposure. The subsequent Phase 3 trial (NCT03569007) evaluated larazotide against placebo for relief of persistent symptoms over a 12-week period in patients already on a gluten-free diet, but was terminated before reporting a definitive dose-response efficacy result, after an interim analysis did not support continuing the trial.

Amounts studied in animal research

Not consistently reported in the sources reviewed for this entry; larazotide’s public trial record is dominated by its human clinical program rather than a widely cited animal dosing literature.

Practitioner and community-reported protocols

Because larazotide has never been an approved or commercially marketed drug, there is not an established practitioner-prescribed dosing convention outside its clinical trials. Some compounding pharmacies and research-chemical vendors offer “larazotide” products referencing the 0.5–2 mg oral, multiple-times-daily range used in trials, but these are not clinically validated, approved, or standardized protocols. Community and vendor material largely repeats the trial dose figures rather than reporting independently derived protocols. Evidence category: community/vendor reported, tracing back to the published trial doses rather than an independent origin.

Side effects, risks, and limitations

Across its published trials, larazotide has generally been reported as well tolerated, with gastrointestinal adverse effects (such as headache, nausea, and mild GI upset) reported at rates similar to or only modestly above placebo, consistent with a drug intended to act locally in the gut with limited systemic absorption. However, because the pivotal Phase 3 trial was terminated for futility rather than completed and fully reported, a complete, confirmatory safety and efficacy dataset from that trial is not available. Key limitations include: efficacy results across the trial program have been inconsistent between studies and endpoints (some Phase 2 measures reached statistical significance while others, and ultimately the Phase 3 primary endpoint outlook, did not); the drug has not been evaluated long-term outside trial settings; and any larazotide obtained outside a regulated clinical trial or approved pharmaceutical supply chain (for example, from research-chemical vendors) carries the same purity, identity, and quality-control uncertainties that apply to any unapproved peptide product.

Regulatory and developmental status

Larazotide acetate is not approved by the FDA or any other major regulatory agency for any indication. Its most advanced program was a Phase 3 trial in celiac disease patients with persistent symptoms on a gluten-free diet (NCT03569007, sponsor 9 Meters Biopharma, enrollment 307), which began in 2019 and was terminated in 2022 after an interim analysis indicated the study was unlikely to meet its primary endpoint (a binary responder analysis based on reduction in Celiac Disease Patient-Reported Outcome Abdominal Domain scores); the sponsor publicly announced that the interim analysis did not support continuing the trial. Earlier programs included a completed Phase 2b dose-ranging trial (NCT01396213) and a Phase 1b/2b gluten-challenge study (NCT00889473), both completed by 2013. Separately, smaller investigator-initiated Phase 2 studies of larazotide in Long COVID (NCT05747534, completed) and pediatric MIS-C (NCT05022303, terminated) have been run by Massachusetts General Hospital, independent of the celiac disease development program; these are not evidence of progress toward approval for celiac disease. As of the last verified date, no active, ongoing pivotal registration trial for larazotide in celiac disease was identified. Date verified: 2026-09-20.

Frequently asked questions

What is larazotide acetate?

It is a synthetic peptide drug candidate (AT-1001) designed to block zonulin-driven opening of intestinal tight junctions, studied primarily as an add-on treatment for celiac disease symptoms.

Did larazotide pass its Phase 3 trial?

No. Its Phase 3 trial (NCT03569007) was terminated in 2022 after an interim analysis showed it was unlikely to meet its primary endpoint; the sponsor, 9 Meters Biopharma, discontinued the study rather than complete it.

What dosage was studied in clinical trials?

The main Phase 2 dose-ranging trial tested 0.5 mg, 1 mg, and 2 mg doses taken three times daily over 12 weeks, in addition to a gluten-free diet.

Is larazotide approved for celiac disease?

No. It is not approved by the FDA or any other major regulator and is not commercially available as a prescription medication.

Does larazotide replace the need for a gluten-free diet?

No. In every trial conducted, larazotide was studied as an adjunct to an ongoing gluten-free diet, not as a substitute for it.

Has larazotide been studied for conditions other than celiac disease?

Yes, in smaller, separate investigator-initiated trials for Long COVID and pediatric multisystem inflammatory syndrome (MIS-C), based on the same proposed gut-permeability mechanism; these are exploratory and not part of the original celiac disease development program.

What side effects have been reported?

Trials have generally reported mild gastrointestinal effects such as headache and nausea, at rates similar to placebo in most studies, though a full safety dataset from the terminated Phase 3 trial was not completed.

Who developed larazotide?

It was originally developed by Alba Therapeutics as AT-1001, later advanced by Innovate Biopharmaceuticals, which became 9 Meters Biopharma.

What remains unknown?

Whether any future trial design could demonstrate a clear, reproducible clinical benefit; why efficacy signals were inconsistent across the drug’s trial history; and whether development will continue given the Phase 3 outcome.

Bottom line

Larazotide acetate has a genuinely deep clinical trial history for a peptide of this kind, including a large Phase 2 dose-ranging study and a full Phase 3 program — which is more rigorous testing than most peptides discussed on this site have received. But that same trial history ends, as of the last verified update, with the pivotal Phase 3 trial stopped for futility, not with a positive, approvable result. It has real published human dosing data (0.5–2 mg TID studied in Phase 2), but no confirmed clinical benefit sufficient for approval, and no established role outside of clinical trials.