AT-1001; CedLara (Phase 3 trial designation) · Evidence-based safety and harm-reduction overview.
| Also known as | AT-1001; CedLara (Phase 3 trial designation) |
| Category | Peptide (research chemical) |
| Structure | Synthetic 8-amino-acid peptide (octapeptide); derived from Vibrio cholerae ZOT |
| Drug class | Zonulin antagonist; tight junction regulator; gut barrier peptide |
| Primary indication studied | Persistent symptoms of celiac disease in patients on a gluten-free diet |
| Development status | Phase 3 (CedLara / NCT03569007) discontinued after interim futility analysis; no active program as of July 2026 |
| Developer | 9 Meters Biopharma, Inc. (NASDAQ); program status post-discontinuation unknown |
| Systemic absorption | Parent compound and metabolites undetectable in serum in human trials; local gut action only |
| US legal status | Investigational drug in the United States; no FDA approval has been granted and no New Drug Application (NDA) has been filed. Development is currently stalled following discontinuation of the Phase 3 CedLara trial by 9 Meters Biopharma, Inc. after an interim futility analysis. Holds FDA Fast Track designation and a Thorough QT study waiver. Not approved for any indication. Not legally available for human use outside of a clinical trial context. |
Larazotide acetate is a synthetic 8-amino-acid peptide (octapeptide) derived from the Vibrio cholerae zonula occludens toxin (ZOT). It acts as a zonulin antagonist - the functional opposite of its parent molecule - by competitively blocking zonulin at intestinal epithelial receptors, thereby preventing disassembly of tight junctions in the gut lining. It was developed primarily as an adjunct therapy for celiac disease (CeD) to reduce intestinal permeability and persistent GI symptoms in patients adhering to a gluten-free diet. Its mechanism is distinct from other investigational celiac therapeutics such as transglutaminase inhibitors or gluten-sequestering agents.
Larazotide acetate competitively occupies zonulin receptors on intestinal epithelial cells, preventing the native zonulin signaling cascade that normally leads to tight junction disassembly. Downstream effects include redistribution and stabilization of tight junction proteins (claudin, occludin, and zonula occludens-1), inhibition of myosin light chain kinase (MLCK), and reduction of actin filament tension, collectively facilitating paracellular closure. This mechanistically blocks the translocation of gliadin fragments - and theoretically other luminal antigens - across the epithelial barrier. More recent preclinical work (2024-2025) has identified additional ROCK inhibition as a contributory pathway, evidenced by reduced phosphorylated myosin light chain 2 (pMLC-2) levels in barrier-injured intestinal tissue. The peptide appears to act locally within the gut; parent compound and metabolites are undetectable in serum in human pharmacokinetic studies, suggesting negligible systemic absorption.
Larazotide acetate originated from research into ZOT, a Vibrio cholerae protein that opens intestinal tight junctions by mimicking the endogenous zonulin pathway. Investigators identified that a derived peptide fragment could antagonize this pathway rather than activate it. The compound was designated AT-1001 in early development and advanced through Phase 1 and Phase 2 trials with the primary indication of celiac disease. A pivotal Phase 2b randomized controlled trial in 342 subjects on a stable gluten-free diet demonstrated that only the 0.5 mg dose met its primary endpoint - higher doses (1 mg, 2 mg) were ineffective, producing a non-monotonic dose-response curve that complicated dose selection. The trial was published in Gastroenterology in 2015. 9 Meters Biopharma subsequently advanced the compound to Phase 3 under the CedLara program (NCT03569007), receiving FDA Fast Track designation. The Phase 3 trial was discontinued following an interim analysis that indicated an excessive sample-size requirement would be needed to achieve statistical significance, making completion impractical. As of mid-2026, no new sponsor or restart has been announced.
All available human efficacy data derive from Phase 1, Phase 2, and one discontinued Phase 3 trial. Approximately 600 subjects were exposed across Phase 1-2 studies with a favorable safety profile. The Phase 2b primary publication (Gastroenterology, 2015) reported a 26% decrease in symptomatic days and a 31% increase in improved symptom days at the 0.5 mg dose in celiac patients on a gluten-free diet who had persistent symptoms. The 1 mg and 2 mg doses did not replicate this benefit. Headache and fatigue were reduced at the active dose in some analyses. Preclinical data include tight junction restoration in porcine intestinal models and prevention of gliadin-induced paracellular permeability in cultured epithelial monolayers. The Phase 3 trial (NCT03569007) was discontinued due to futility at interim analysis - not safety signals. No data from the Phase 3 cohort have been published as of the research date. Current development status is stalled with no active clinical program known to be running as of July 2026.
In Phase 2b human trials, the 0.5 mg oral dose administered three times daily before meals was the only dose that met the primary efficacy endpoint; 1 mg and 2 mg TID doses were not effective. These are literature-reported trial doses only and are provided for informational reference. This does not constitute a dosing protocol or recommendation. Larazotide acetate is not an approved drug and is not available for prescription or self-administration. Any clinical use would require consultation with a physician within an approved investigational context.
This is general research/context information, not medical advice or a recommended protocol.
No human data exist on combining larazotide acetate with other compounds. Its mechanism as a tight junction regulator is conceptually orthogonal to gluten-digesting enzyme therapies (e.g., AN-PEP, ALV003) and immune-modulating approaches, but no combination trials have been conducted. Speculation about synergy is unsupported by published evidence.
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Get tested with Ulta Lab Tests →The Phase 2b results were only positive at the lowest dose tested (0.5 mg), and the effect size - while statistically significant - was modest. When 9 Meters Biopharma conducted an interim analysis of the Phase 3 CedLara trial (NCT03569007), the projection indicated that achieving statistical significance at the chosen endpoints would require an impractically large sample size. This is a common scenario where a Phase 2 signal does not replicate cleanly in a larger, more rigorous Phase 3 design. The discontinuation was driven by futility projection, not safety concerns.
No. Larazotide acetate is an unapproved investigational drug with no approved indication in the United States or elsewhere. It is not commercially available as a pharmaceutical. No legitimate supply chain exists for non-research use. Peptide synthesis vendors may be capable of producing the sequence, but such material would have no regulatory oversight or quality assurance.
In the Phase 2b trial, only the 0.5 mg three-times-daily dose met the primary endpoint. The 1 mg and 2 mg doses did not demonstrate efficacy, producing a non-monotonic dose-response relationship that is not fully explained by available data. This dosing information is from published trial literature and is not a dosing recommendation. Consult a clinician for any clinical questions.
Intestinal tight junction regulation is a biologically plausible target in multiple conditions involving increased gut permeability, including inflammatory bowel disease, irritable bowel syndrome, and systemic inflammatory conditions. However, no clinical trials in non-celiac populations have produced published efficacy data for larazotide acetate. Any such application would remain speculative and unsupported by human evidence at this time.
Human pharmacokinetic data from trials found the parent compound and its metabolites undetectable in serum. This profile supports the hypothesis of local luminal action and was cited by the FDA in granting a Thorough QT study waiver - meaning the FDA agreed systemic cardiac exposure risk was sufficiently low to waive a required cardiac safety study. No serious systemic adverse events were reported across approximately 600 exposed subjects in Phase 1-2 programs.
As of July 2026, the outlook is uncertain. 9 Meters Biopharma discontinued the CedLara Phase 3 program and indicated the possibility of re-engagement with the FDA based on analysis of existing data, but no new trial initiation or partnership announcement has been made publicly available. Without acquisition by a new sponsor or compelling new data framing a different trial design, advancement appears unlikely in the near term.
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