Larazotide acetate
Also known as: Larazotide, AT-1001, INN-202, Larazotide acetate
Key Facts: Larazotide acetate
- Category
- Immune
- FDA Status
- Not FDA Approved
- Clinical Status
- Investigational, not approved anywhere. Phase 3 celiac trial (CedLara, NCT03569007) terminated in 2022 after interim analysis; sponsor 9 Meters Biopharma filed for Chapter 7 liquidation in July 2023. No known active development.
- Banned in Sport (WADA)
- Not named on the WADA list, but WADA's S0 catch-all (non-approved substances) covers any substance without human therapeutic approval, which includes larazotide. Prohibited at all times.
- Administration
- Oral capsule taken before meals, alongside a gluten-free diet (not instead of it)
- Typical Dose
- 0.5 mg three times daily before meals (trial dose)
- Frequency
- Three times daily, before meals
- Duration
- 12 weeks of treatment in the phase 2b trial
How does Larazotide acetate work?
Larazotide is modeled on a fragment of Vibrio cholerae zonula occludens toxin, a region that overlaps with zonulin, the human protein that loosens tight junctions in the gut wall. The idea is that it blocks zonulin signaling and helps tight junctions reassemble, so gluten fragments have a harder time slipping between cells into the tissue underneath, where they trigger the immune reaction in celiac disease. It acts locally in the gut lumen and is not meant to be absorbed. That is a reasonable hypothesis with lab and animal support, but it is worth being clear: larazotide does not stop the immune response to gluten itself, and no human trial proved it protects the gut lining on biopsy.
What does the research show?
The key human study is a phase 2b trial published in Gastroenterology in 2015 (Leffler and colleagues, NCT01396213). It randomized 342 adults with celiac disease who still had symptoms on a gluten-free diet to 0.5 mg, 1 mg, or 2 mg three times daily or placebo for 12 weeks. Only 0.5 mg met the primary endpoint (symptom score 2.59 vs 2.88), with 26% fewer symptomatic days. The 1 mg and 2 mg doses did nothing measurable, an odd inverse dose response the authors could not explain (peptide aggregation was one guess), and most secondary endpoints missed. Safety looked similar to placebo. The phase 3 CedLara trial (NCT03569007) then tested the same 0.5 mg dose, but in June 2022 an interim analysis showed the number of patients needed to separate drug from placebo was too large to continue, and the trial was terminated. 9 Meters later pointed larazotide at COVID-related conditions such as MIS-C, then filed Chapter 7 in July 2023. We found no active development after that. Bottom line: one positive-ish phase 2b, one stopped phase 3, no approval.
What doses have been studied?
Typical Dosingⓘ
Community experience
0.5 mg three times daily before meals (trial dose)
0.5-2 mg three times daily tested; only 0.5 mg showed any effect
Three times daily, before meals
These are clinical trial doses, not a recommendation. Larazotide was always tested as an add-on to a strict gluten-free diet, never as a way to eat gluten. The higher doses did not work in phase 2b, and the phase 3 at 0.5 mg was halted.
Research Dosingⓘ
Scientific studies
Trial doses only (no approved dose exists)
Doses from Studies
0.5 mg three times daily
Phase 2b RCT (trial dose) - Leffler et al., Gastroenterology 2015;148(7):1311-1319 (PMID 25683116) ↗
0.5 mg three times daily
Duration
12 weeks of treatment in the phase 2b trial
Administration
Oral capsule taken before meals, alongside a gluten-free diet (not instead of it)
When and how is Larazotide acetate taken?
Best Time to Take
About 15 minutes before each main meal (trial protocol)
Three times daily before meals in trials
Food Recommendation
With or without food
Why This Timing?
It acts locally in the gut, so the trials timed it to be in place before food (and any stray gluten) arrived.
What are the side effects of Larazotide acetate?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●GI complaints at rates similar to placebo in phase 2b
- ●Headache
- ●No drug-related serious adverse events reported in phase 2b
- ●Long-term safety unknown (no trial ran past a few months)
- ●Quality and identity of non-trial material are unknown
References
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4446229
- https://clinicaltrials.gov/study/NCT01396213
- https://clinicaltrials.gov/study/NCT03569007
- https://www.beyondceliac.org/research-news/phase-3-study-discontinued/
- https://www.sec.gov/Archives/edgar/data/1551986/000093041323001864/c106716_8k-ixbrl.htm
Research This Peptide Further
Frequently Asked Questions
What does Larazotide acetate do?
Larazotide is an 8-amino-acid oral peptide (GGVLVQPG) designed to tighten the junctions between gut lining cells, aimed at celiac disease. For years it was the furthest-along celiac drug in development and it gets talked about online as a 'leaky gut' or zonulin blocker. The honest story is short: one phase 2b trial found a modest symptom benefit at the lowest dose only, the phase 3 trial was stopped in 2022 when it could not show a clear effect, and the sponsor 9 Meters Biopharma filed for Chapter 7 liquidation in July 2023. It is not approved anywhere.
How does Larazotide acetate work?
Larazotide is modeled on a fragment of Vibrio cholerae zonula occludens toxin, a region that overlaps with zonulin, the human protein that loosens tight junctions in the gut wall. The idea is that it blocks zonulin signaling and helps tight junctions reassemble, so gluten fragments have a harder time slipping between cells into the tissue underneath, where they trigger the immune reaction in celiac disease. It acts locally in the gut lumen and is not meant to be absorbed. That is a reasonable hypothesis with lab and animal support, but it is worth being clear: larazotide does not stop the immune response to gluten itself, and no human trial proved it protects the gut lining on biopsy.
Is Larazotide acetate FDA approved?
No, Larazotide acetate is not currently FDA approved. Current status: Investigational, not approved anywhere. Phase 3 celiac trial (CedLara, NCT03569007) terminated in 2022 after interim analysis; sponsor 9 Meters Biopharma filed for Chapter 7 liquidation in July 2023. No known active development.
Is Larazotide acetate banned in sport?
Not named on the WADA list, but WADA's S0 catch-all (non-approved substances) covers any substance without human therapeutic approval, which includes larazotide. Prohibited at all times.
What are the side effects of Larazotide acetate?
Reported side effects include: GI complaints at rates similar to placebo in phase 2b, Headache, No drug-related serious adverse events reported in phase 2b, Long-term safety unknown (no trial ran past a few months), Quality and identity of non-trial material are unknown. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Larazotide acetate?
Community-reported common dose: 0.5 mg three times daily before meals (trial dose) (Three times daily, before meals). Range: 0.5-2 mg three times daily tested; only 0.5 mg showed any effect. Administration: Oral capsule taken before meals, alongside a gluten-free diet (not instead of it). Community-reported doses. Not medical advice. Consult healthcare provider.
Related Peptides
Peptides commonly compared with Larazotide acetate or used in similar applications.
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