Peptide education
Larazotide acetate
Larazotide · AT-1001 · INN-202
Larazotide acetate is an investigational oral peptide studied for celiac symptoms that continue despite a gluten-free diet. It was designed to influence junctions between intestinal cells.
One phase 2 dose group reported fewer symptoms than placebo. The later celiac phase 3 study stopped after an interim sample-size assessment, leaving the earlier finding without completed phase 3 confirmation.
Overview
Quick answer
The celiac trials studied larazotide alongside dietary management. They did not establish that it prevents intestinal injury from eating gluten.
What was larazotide studied for?
A phase 2 trial enrolled adults with celiac disease who still had symptoms while following a gluten-free diet. Participants continued the diet during treatment.
Did the phase 2 trial find a benefit?
The 0.5 mg group had lower average gastrointestinal symptom scores than placebo during 12 weeks. The 1 mg and 2 mg groups did not show statistically significant differences from placebo on the reported endpoints.
What happened in phase 3?
The sponsor discontinued the celiac study after an interim assessment indicated that the additional enrollment needed to detect a significant difference would be too large to support continuation. The trial registry lists it as terminated.
Can it replace a gluten-free diet?
No trial established that larazotide can replace the diet or protect against intestinal injury from gluten. The symptom trial kept the diet in place, and a separate permeability study had inconclusive results.
Evidence
Evidence snapshot
The 0.5 mg group improved on the primary symptom measure versus placebo; the higher-dose groups did not show the same result.
In an exploratory gluten-challenge trial, variability in the test limited assessment of the effect on intestinal permeability.
The sponsor stopped the trial after its interim sample-size reassessment; the registry does not contain a completed phase 3 result.
A separate phase 2 long COVID study is registered as completed. The registry does not contain results.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Larazotide reduced celiac symptoms in a controlled study. | In a randomized trial, the 0.5 mg group had lower average symptom scores than placebo; the 1 mg and 2 mg groups did not. | A real phase 2 signal, but an inconsistent dose pattern and an unfinished phase 3 study leave the clinical benefit unresolved. | |
| It closes the gut barrier in people with celiac disease. | The exploratory gluten-challenge study could not reliably determine an effect on its permeability measure because of test variability. | The drug was designed as a tight-junction regulator; that proposed action does not establish the same effect in patients. | The clinical permeability claim is not established by that trial. |
| A stopped trial proves the drug has no effect. | The sponsor said an interim sample-size reassessment made the trial too large to continue. The prior phase 2 trial had reported a lower-dose signal. | The phase 3 study did not produce a completed confirmatory estimate; its termination does not erase or conclusively validate the earlier finding. |
Bottom line
Main takeaway
Larazotide is an experimental celiac research drug, not a proven way to eat gluten safely.
A symptom improvement in one phase 2 group is meaningful to investigate, but it is not the same as a completed phase 3 confirmation.
Symptom scores and lactulose-to-mannitol permeability measurements answer different questions and did not produce the same clarity in the studies.
Identity
What it is
Larazotide is an eight-amino-acid peptide. The phase 3 registration describes an oral capsule containing enteric-coated beads.
The celiac phase 2 symptom trial included adults with ongoing symptoms despite at least a year on a gluten-free diet.
Use context
Routes, doses, and cycle patterns
The celiac studies used oral larazotide alongside a gluten-free diet. Their doses and outcomes belonged to controlled research settings.
Human studies and product labels
Phase 2 symptom trial
- Context
- Adults with celiac disease and persistent symptoms
- Route
- Oral
- Amount
- 0.5 mg, 1 mg, or 2 mg per dose
- Frequency
- Three times daily
- Duration
- 12 weeks
The 0.5 mg group met the primary symptom endpoint; higher doses did not show statistically significant differences from placebo on the reported endpoints.
Celiac phase 3 registration
- Context
- Adults with persistent symptoms on a gluten-free diet
- Route
- Oral capsule
- Amount
- 0.25 mg or 0.5 mg per dose
- Frequency
- Three times daily
The study was terminated after the sponsor's interim sample-size reassessment. The registration does not provide a completed result.
Research
Research evidence
The phase 2 symptom study found a lower-dose signal; the gluten-challenge study could not reliably establish a permeability effect. The celiac phase 3 trial did not finish its planned confirmation.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Phase 2 celiac symptom trial | 342 adults with celiac disease and persistent symptoms | Randomized, double-blind, placebo-controlled, dose-ranging trial | Oral larazotide three times daily for 12 weeks with a gluten-free diet | The 0.5 mg dose improved the average on-treatment gastrointestinal symptom score versus placebo. The 1 mg and 2 mg doses did not show statistically significant differences from placebo on the reported endpoints. | The mixed dose response and lack of phase 3 confirmation limit interpretation. | Controlled human evidence with unresolved clinical benefit |
| Gluten-challenge study | 86 people with diet-controlled celiac disease | Exploratory randomized, placebo-controlled dose-ranging study | Oral larazotide with or without a controlled gluten challenge | Variability in the lactulose-to-mannitol test prevented a reliable assessment of permeability; some lower-dose groups showed differences in symptoms. | Small groups and a variable biomarker prevent firm conclusions about barrier protection. | Limited exploratory human evidence |
| Celiac phase 3 registration and sponsor update | Adults with persistent symptoms on a gluten-free diet | Randomized, blinded, placebo-controlled study terminated early | Oral larazotide capsules | The sponsor decided not to continue after estimating that substantially more participants would be needed to detect a significant difference. | The trial did not provide a completed confirmatory efficacy estimate in the registry. | Development-status evidence |
Cautions
Safety and unknowns
- The phase 2 symptom trial reported a safety profile comparable with placebo over its study period; that does not settle rare or long-term harms.
- Symptom improvement is not proof that gluten-related intestinal damage is prevented. Participants in the symptom study continued a gluten-free diet.
- A separate long COVID trial is recorded as completed, but its registry does not provide results.
Mechanism
How it is proposed to work
Larazotide was designed to affect the junctions between cells in the intestinal lining, which help regulate movement between those cells.
Laboratory tight-junction effects provide a rationale for testing the peptide, but the human gluten-challenge study could not resolve its effect on the permeability measure used.
The symptom endpoint and a measure of barrier permeability should not be treated as interchangeable evidence.
Details
Technical details
Sources
References
- 1.
PubMed. Larazotide acetate for persistent celiac symptoms on a gluten-free diet
doi:10.1053/j.gastro.2015.02.008 PMID:25683116 NCT01396213
Randomized dose-ranging trial in adults with persistent celiac symptoms.
- 2.
PubMed. Larazotide acetate and gluten challenge in celiac disease
doi:10.1038/ajg.2012.211 PMID:22825365
Randomized exploratory trial measuring permeability and symptoms under gluten challenge.
- 3.
ClinicalTrials.gov. Larazotide phase 3 celiac trial registry
NCT03569007
Registry identifies the terminated study and its treatment arms.
- 4.
Other. Sponsor filing on the celiac phase 3 interim analysis
Sponsor explains the sample-size reassessment and decision to discontinue the celiac program.
- 5.
ClinicalTrials.gov. Larazotide long COVID phase 2 trial registry
NCT05747534
A separate completed study with no results posted in the registry.