Larazotide

updated September 11, 2026

Larazotide acetate showed a symptom benefit at 0.5 mg three times daily in one 12-week celiac trial, while 1 mg and 2 mg did not. The pivotal celiac phase 3 study was stopped after an interim analysis, and a separate 107-person Long COVID study is complete with no results posted.

Oral tight-junction regulator peptide

Eight-amino-acid peptide
Also called AT-1001 and INN-202
Studied in an enteric-coated oral formulation
No approved U.S. prescribing label found

What did the published celiac trial actually find?

In 342 adults with celiac disease who still had symptoms despite at least 12 months on a gluten-free diet, 0.5 mg larazotide acetate three times daily improved the average on-treatment gastrointestinal symptom score versus placebo. The primary analysis gave P = 0.022, with P = 0.005 in the repeated-measures model.

The treatment lasted 12 weeks after a 4-week placebo run-in. The drug was an adjunct to the participants' existing gluten-free diet, not a replacement for it.

Phase 2b celiac trial · 0.5 mg signal

Randomized controlled trial

Leffler et al., Gastroenterology, 2015

Among 342 adults with persistent celiac symptoms on a gluten-free diet, 0.5 mg three times daily met the gastrointestinal symptom primary endpoint versus placebo. The 1 mg and 2 mg groups did not differ from placebo on any endpoint, and short-term safety was comparable.

Primary analysis at 0.5 mg: P = 0.022
Repeated-measures analysis at 0.5 mg: P = 0.005
Higher doses did not separate

Participants / model: Adults with celiac disease, persistent symptoms, and at least 12 months on a gluten-free diet
Treatment: Larazotide acetate 0.5, 1, or 2 mg three times daily versus placebo; gluten-free diet continued
Follow-up: 4-week placebo run-in, 12-week treatment, 4-week run-out
Study design: Multicenter randomized double-blind placebo-controlled phase 2b trial

The positive dose was not supported by the two higher-dose arms and has not been confirmed in a successful pivotal trial.

Read the original source

Did the trial show a consistent dose response?

The 1 mg and 2 mg three-times-daily groups were no different from placebo on any endpoint. Only the lowest tested dose met the primary endpoint, so the study did not show a conventional increasing dose response.

Exploratory results at 0.5 mg included 26% fewer symptomatic days and 31% more improved-symptom days. Those were secondary findings from the same trial, not independent replications.

Phase 2b celiac trial · 0.5 mg signal

Randomized controlled trial

Leffler et al., Gastroenterology, 2015

Among 342 adults with persistent celiac symptoms on a gluten-free diet, 0.5 mg three times daily met the gastrointestinal symptom primary endpoint versus placebo. The 1 mg and 2 mg groups did not differ from placebo on any endpoint, and short-term safety was comparable.

Primary analysis at 0.5 mg: P = 0.022
Repeated-measures analysis at 0.5 mg: P = 0.005
Higher doses did not separate

Participants / model: Adults with celiac disease, persistent symptoms, and at least 12 months on a gluten-free diet
Treatment: Larazotide acetate 0.5, 1, or 2 mg three times daily versus placebo; gluten-free diet continued
Follow-up: 4-week placebo run-in, 12-week treatment, 4-week run-out
Study design: Multicenter randomized double-blind placebo-controlled phase 2b trial

The positive dose was not supported by the two higher-dose arms and has not been confirmed in a successful pivotal trial.

Read the original source

Why was the pivotal CeDLara trial terminated?

CeDLara randomized 307 participants before the sponsor terminated it. The sponsor's SEC filing says an independent interim analysis indicated that the additional sample needed for a significant placebo difference would be too large to support continuation. The registry has no posted results.

The registry's public reason says only "Trial terminated by Sponsor." The SEC filing supplies the interim-analysis context. Neither source provides an efficacy estimate for the 307 participants.

CeDLara · terminated with no results

Clinical trial registry record

ClinicalTrials.gov, NCT03569007

The phase 3 celiac study lists 307 actual participants, terminated status, a July 21, 2022 completion date, and no posted results. The public reason is "Trial terminated by Sponsor."

Participants / model: Adults with celiac disease and persistent symptoms despite a gluten-free diet
Treatment: Enteric-coated larazotide 0.25 mg or 0.50 mg three times daily versus placebo
Follow-up: Terminated; actual completion July 21, 2022
Study design: Randomized triple-masked placebo-controlled phase 3 trial
Funding: 9 Meters Biopharma

The registry does not post outcome data and gives no numerical futility boundary.

Read the original source

Sponsor filing · CeDLara interim decision

SEC filing

9 Meters Biopharma, Form 10-K for 2022

The company reported that an independent interim analysis found the additional number of participants needed to reach a significant placebo difference would be too large to support continuation, after which it discontinued celiac development.

The filing also describes the enteric-coated multiparticulate oral formulation.

Participants / model: CeDLara celiac development program
Treatment: Larazotide acetate
Follow-up: Decision disclosed for June 2022
Study design: Sponsor regulatory and financial disclosure
Funding: Company filing

This explains the sponsor's decision but is not a substitute for participant-level or posted trial results.

Read the original source

What is the current status of the Long COVID trial?

NCT05747534 is completed, with 107 actual participants and a June 18, 2026 completion date. It tested larazotide against placebo in people ages 7 through 50, but the registry posts no results.

The research schedule was 250 or 500 micrograms by body weight, taken four times daily for 21 days, with adverse events and symptom resolution assessed over 8 weeks. That is a monitored study protocol, not routine-use guidance.

NCT05747534 · completed, no results

Clinical trial registry record

ClinicalTrials.gov, NCT05747534

The randomized phase 2 study is completed with 107 actual participants and no posted results. It tested 21 days of weight-banded larazotide or placebo and assessed adverse events and symptom resolution over 8 weeks.

Actual completion June 18, 2026
The registry posts no results.

Participants / model: Children, adolescents, and adults ages 7 through 50 with Long COVID
Treatment: Oral larazotide acetate 250 micrograms below 25 kg or 500 micrograms at or above 25 kg, four times daily, versus placebo
Follow-up: 21 days treatment; 8-week primary assessment
Study design: Randomized quadruple-masked placebo-controlled phase 2 trial
Funding: Massachusetts General Hospital

Completion does not establish benefit or safety while the result tables remain absent.

Read the original source

How is larazotide supposed to work, and does it enter the blood?

The studied enteric-coated formulation was designed to release an octapeptide in the small intestine and regulate epithelial tight junctions. The proposed pathway involves zonulin signaling and cytoskeletal junction proteins, but the precise receptor-level mechanism remains unsettled.

"Gut restricted" describes the low systemic exposure of the studied formulation. It does not establish zero absorption or equivalence to a different oral product.

Mechanism review · gut-targeted formulation

Peer-reviewed mechanistic review

Slifer and Blikslager, American Journal of Physiology Gastrointestinal and Liver Physiology, 2021

The review describes larazotide as an eight-amino-acid, intestine-targeted tight-junction regulator and summarizes proposed zonulin, cytoskeletal, and myosin-light-chain-kinase pathways. It also notes unresolved details in the proposed receptor pathway.

Participants / model: Cell, animal, formulation, and clinical literature
Treatment: Larazotide acetate
Follow-up: Literature through publication
Study design: Narrative mechanistic review

This 2021 mechanism review predates the 2022 CeDLara termination and provides no current approval or clinical efficacy result.

Read the original source

Sponsor filing · CeDLara interim decision

SEC filing

9 Meters Biopharma, Form 10-K for 2022

The company reported that an independent interim analysis found the additional number of participants needed to reach a significant placebo difference would be too large to support continuation, after which it discontinued celiac development.

The filing also describes the enteric-coated multiparticulate oral formulation.

Participants / model: CeDLara celiac development program
Treatment: Larazotide acetate
Follow-up: Decision disclosed for June 2022
Study design: Sponsor regulatory and financial disclosure
Funding: Company filing

This explains the sponsor's decision but is not a substitute for participant-level or posted trial results.

Read the original source

Is larazotide an approved or commercially established medicine?

The cited FDA records list no approved larazotide product or prescribing label. The celiac program did not reach approval, and the completed Long COVID trial has not posted results.

None of the investigational studies, emergency IND uses, patents, or formulation records provides a marketing authorization or prescribing label.

FDA records · no approved label

FDA drug records

Drugs@FDA and FDA labeling records for larazotide and its aliases.

The cited U.S. FDA records list no approved product or prescribing label under larazotide, larazotide acetate, AT-1001, or INN-202.

Participants / model: United States marketing authorizations
Treatment: Larazotide aliases

The cited databases cover U.S. drug approval; they do not establish commercial status elsewhere.

Read the original source

CeDLara · terminated with no results

Clinical trial registry record

ClinicalTrials.gov, NCT03569007

The phase 3 celiac study lists 307 actual participants, terminated status, a July 21, 2022 completion date, and no posted results. The public reason is "Trial terminated by Sponsor."

Participants / model: Adults with celiac disease and persistent symptoms despite a gluten-free diet
Treatment: Enteric-coated larazotide 0.25 mg or 0.50 mg three times daily versus placebo
Follow-up: Terminated; actual completion July 21, 2022
Study design: Randomized triple-masked placebo-controlled phase 3 trial
Funding: 9 Meters Biopharma

The registry does not post outcome data and gives no numerical futility boundary.

Read the original source

NCT05747534 · completed, no results

Clinical trial registry record

ClinicalTrials.gov, NCT05747534

The randomized phase 2 study is completed with 107 actual participants and no posted results. It tested 21 days of weight-banded larazotide or placebo and assessed adverse events and symptom resolution over 8 weeks.

Actual completion June 18, 2026
The registry posts no results.

Participants / model: Children, adolescents, and adults ages 7 through 50 with Long COVID
Treatment: Oral larazotide acetate 250 micrograms below 25 kg or 500 micrograms at or above 25 kg, four times daily, versus placebo
Follow-up: 21 days treatment; 8-week primary assessment
Study design: Randomized quadruple-masked placebo-controlled phase 2 trial
Funding: Massachusetts General Hospital

Completion does not establish benefit or safety while the result tables remain absent.

Read the original source

How complete is the adverse-effect and interaction record?

In the 12-week celiac phase 2b study, overall safety was comparable with placebo; gastrointestinal disorders were the most frequent treatment-emergent class and no serious adverse event was judged drug related. That short trial cannot define long-term, pediatric, pregnancy, interaction, or rare-harm risks.

Phase 2b celiac trial · 0.5 mg signal

Randomized controlled trial

Leffler et al., Gastroenterology, 2015

Among 342 adults with persistent celiac symptoms on a gluten-free diet, 0.5 mg three times daily met the gastrointestinal symptom primary endpoint versus placebo. The 1 mg and 2 mg groups did not differ from placebo on any endpoint, and short-term safety was comparable.

Primary analysis at 0.5 mg: P = 0.022
Repeated-measures analysis at 0.5 mg: P = 0.005
Higher doses did not separate

Participants / model: Adults with celiac disease, persistent symptoms, and at least 12 months on a gluten-free diet
Treatment: Larazotide acetate 0.5, 1, or 2 mg three times daily versus placebo; gluten-free diet continued
Follow-up: 4-week placebo run-in, 12-week treatment, 4-week run-out
Study design: Multicenter randomized double-blind placebo-controlled phase 2b trial

The positive dose was not supported by the two higher-dose arms and has not been confirmed in a successful pivotal trial.

Read the original source

FDA records · no approved label

FDA drug records

Drugs@FDA and FDA labeling records for larazotide and its aliases.

The cited U.S. FDA records list no approved product or prescribing label under larazotide, larazotide acetate, AT-1001, or INN-202.

Participants / model: United States marketing authorizations
Treatment: Larazotide aliases

The cited databases cover U.S. drug approval; they do not establish commercial status elsewhere.

Read the original source

Studies and sources

Phase 2b celiac trial · 0.5 mg signal

Randomized controlled trial

Leffler et al., Gastroenterology, 2015

Among 342 adults with persistent celiac symptoms on a gluten-free diet, 0.5 mg three times daily met the gastrointestinal symptom primary endpoint versus placebo. The 1 mg and 2 mg groups did not differ from placebo on any endpoint, and short-term safety was comparable.

Primary analysis at 0.5 mg: P = 0.022
Repeated-measures analysis at 0.5 mg: P = 0.005
Higher doses did not separate

Participants / model: Adults with celiac disease, persistent symptoms, and at least 12 months on a gluten-free diet
Treatment: Larazotide acetate 0.5, 1, or 2 mg three times daily versus placebo; gluten-free diet continued
Follow-up: 4-week placebo run-in, 12-week treatment, 4-week run-out
Study design: Multicenter randomized double-blind placebo-controlled phase 2b trial

The positive dose was not supported by the two higher-dose arms and has not been confirmed in a successful pivotal trial.

Read the original source

CeDLara · terminated with no results

Clinical trial registry record

ClinicalTrials.gov, NCT03569007

The phase 3 celiac study lists 307 actual participants, terminated status, a July 21, 2022 completion date, and no posted results. The public reason is "Trial terminated by Sponsor."

Participants / model: Adults with celiac disease and persistent symptoms despite a gluten-free diet
Treatment: Enteric-coated larazotide 0.25 mg or 0.50 mg three times daily versus placebo
Follow-up: Terminated; actual completion July 21, 2022
Study design: Randomized triple-masked placebo-controlled phase 3 trial
Funding: 9 Meters Biopharma

The registry does not post outcome data and gives no numerical futility boundary.

Read the original source

Sponsor filing · CeDLara interim decision

SEC filing

9 Meters Biopharma, Form 10-K for 2022

The company reported that an independent interim analysis found the additional number of participants needed to reach a significant placebo difference would be too large to support continuation, after which it discontinued celiac development.

The filing also describes the enteric-coated multiparticulate oral formulation.

Participants / model: CeDLara celiac development program
Treatment: Larazotide acetate
Follow-up: Decision disclosed for June 2022
Study design: Sponsor regulatory and financial disclosure
Funding: Company filing

This explains the sponsor's decision but is not a substitute for participant-level or posted trial results.

Read the original source

NCT05747534 · completed, no results

Clinical trial registry record

ClinicalTrials.gov, NCT05747534

The randomized phase 2 study is completed with 107 actual participants and no posted results. It tested 21 days of weight-banded larazotide or placebo and assessed adverse events and symptom resolution over 8 weeks.

Actual completion June 18, 2026
The registry posts no results.

Participants / model: Children, adolescents, and adults ages 7 through 50 with Long COVID
Treatment: Oral larazotide acetate 250 micrograms below 25 kg or 500 micrograms at or above 25 kg, four times daily, versus placebo
Follow-up: 21 days treatment; 8-week primary assessment
Study design: Randomized quadruple-masked placebo-controlled phase 2 trial
Funding: Massachusetts General Hospital

Completion does not establish benefit or safety while the result tables remain absent.

Read the original source

Mechanism review · gut-targeted formulation

Peer-reviewed mechanistic review

Slifer and Blikslager, American Journal of Physiology Gastrointestinal and Liver Physiology, 2021

The review describes larazotide as an eight-amino-acid, intestine-targeted tight-junction regulator and summarizes proposed zonulin, cytoskeletal, and myosin-light-chain-kinase pathways. It also notes unresolved details in the proposed receptor pathway.

Participants / model: Cell, animal, formulation, and clinical literature
Treatment: Larazotide acetate
Follow-up: Literature through publication
Study design: Narrative mechanistic review

This 2021 mechanism review predates the 2022 CeDLara termination and provides no current approval or clinical efficacy result.

Read the original source

FDA records · no approved label

FDA drug records

Drugs@FDA and FDA labeling records for larazotide and its aliases.

The cited U.S. FDA records list no approved product or prescribing label under larazotide, larazotide acetate, AT-1001, or INN-202.

Participants / model: United States marketing authorizations
Treatment: Larazotide aliases

The cited databases cover U.S. drug approval; they do not establish commercial status elsewhere.

Read the original source

Why is Larazotide in D tier?

D reflects a mixed, unconfirmed clinical record. One dose met the celiac symptom endpoint, higher doses did not, the pivotal study stopped without results, and the completed Long COVID study has not reported outcomes.