larazotide (AT1001) / 9 Meters Biopharma - LARVOL DELTA

LARAZOTIDE ACETATE: ANALYSIS OF A PHASE # STUDY FOR PERSISTENT SYMPTOMS IN PATIENTS WITH CELIAC DISEASE (DDW 2025) - No abstract available

Clinical • Celiac Disease • Immunology

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Elucidating the Significance of Zonulin in the Pathogenesis of Chronic Inflammatory Disorders: Emphasis on Intestinal Barrier Function and Tight Junction Regulation. (PubMed, Curr Med Chem) - "Recent research has demonstrated the therapeutic potential of targeting zonulin, specifically through the use of larazotide acetate, a zonulin antagonist...Further research is needed to elucidate the precise mechanisms of action of zonulin antagonists and evaluate their efficacy and safety in clinical trials. A deeper understanding of the complex interplay among zonulin, intestinal permeability, and CIDs is crucial, paving the way for novel therapeutic strategies and personalized approaches to patient care."

Journal • Celiac Disease • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Multiple Sclerosis

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2 | N=12 | Terminated | Sponsor: Massachusetts General Hospital | N=20 ➔ 12 | Trial completion date: Dec 2025 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ May 2024; Decline in MISC cases

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2022 ➔ Dec 2025 | Trial primary completion date: Sep 2022 ➔ Jun 2025

Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Novel Coronavirus Disease

Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats. (PubMed, Dig Dis Sci) - "Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects."

Journal • Preclinical • Immunology • Inflammation • Pancreatitis • Systemic Inflammatory Response Syndrome • TJP1

Bromelain and ficin proteolytic effects on gliadin cytotoxicity and expression of genes involved in cell-tight junctions in Caco-2 cells. (PubMed, Amino Acids) - "Finally, we examined the effect of these treatments along with Larazotide Acetate on the expression of genes involved in cell-tight junctions, such as Occludin, Claudin 3, tight junction protein-1, and Zonulin in the Caco-2 cell line. Furthermore, the proteolytic effects of bromelain and ficin on gliadin indicated the expression of genes involved in cell-tight junctions was improved. This study confirms that bromelain and ficin mixture could be effective in improving the symptoms of CeD."

Journal • Celiac Disease • Immunology • CLDN3 • OCLN • TJP1

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2a | N=48 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions. (PubMed, Int J Mol Sci) - "In addition to focusing on the effect of microbiome on intestinal zonulin release, we also summarize potential pharmaceutical approaches to modulate zonulin-associated pathways with larazotide acetate and other zonulin receptor agonists or antagonists. The present review also addresses the emerging issues, including the use of misleading nomenclature or the unsolved questions about the exact protein sequence of zonulin."

Journal • Review • CNS Disorders

AT1001 for the Treatment of Long COVID (clinicaltrials.gov) - P2a | N=48 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2a trial • Infectious Disease • Novel Coronavirus Disease

Sex-dependent Lupus Blautia (Ruminococcus) gnavus strain induction of zonulin-mediated intestinal permeability and autoimmunity. (PubMed, Front Immunol) - "Strikingly, gut permeability was completely reversed by oral treatment with larazotide acetate, an octapeptide that is a specific molecular antagonist of zonulin. Taken together, these studies document a pathway by which RG strains from Lupus patients contribute to a leaky gut and features of autoimmunity implicated in the pathogenesis of flares of clinical Lupus disease."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms (clinicaltrials.gov) - P3 | N=307 | Terminated | Sponsor: 9 Meters Biopharma, Inc. | N=630 ➔ 307 | Trial completion date: Dec 2021 ➔ Jul 2022 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2021 ➔ Jul 2022; Trial terminated by Sponsor

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Celiac Disease • Immunology

Modulation of the Intestinal Tight Junction Reduces Lung Fibrosis in an Animal Model for Idiopathic Pulmonary Fibrosis: The Role of Intestinal Microbiome Gut-Lung Axis in Idiopathic Pulmonary Fibrosis (ATS 2022) - "Methods - Forty-eight pathogen-free, 6-week old, female C57BL/6J mice were induced to develop pulmonary fibrosis by a single intratracheal administration of bleomycin (3.0 mg/kg). On the following 20 days, mice were administered once daily with larazotide orally (1 mg/kg), larazotide intratracheally (25 μg/mouse), vehicle (control) or dexamethasone (0.25 mg/kg, active control)...Conclusions - In an animal model for IPF, the tight-junction modulator larazotide administered orally reduced pulmonary fibrosis better than administered intratracheally, indicating that the gut microbiome may play an important role in pulmonary fibrosis. Therefore, intestinal tight junction modulators, such as larazotide, may have a role in the treatment of IPF via gut-lung axis."

Preclinical • Allergy • Asthma • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Fibrosis • Genetic Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series. (PubMed, Crit Care Explor) - "Larazotide appears safe and well-tolerated and may offer potential benefit as an adjuvant to immune-targeted therapies. Expansion of clinical trials is urgently needed to ascertain the clinical impact of larazotide on MIS-C."

Journal • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats. (PubMed, Hum Exp Toxicol) - "Our findings suggest that LA reduced intestinal damage by acting on TJs in the TAA-induced ALF model in rats."

Journal • Preclinical • Celiac Disease • Hepatology • Immunology • Liver Failure

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2a; N=20; Recruiting; Sponsor: Massachusetts General Hospital; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

Peptide Derivatives of the Zonulin Inhibitor Larazotide (AT1001) as Potential Anti SARS-CoV-2: Molecular Modelling, Synthesis and Bioactivity Evaluation. (PubMed, Int J Mol Sci) - "Thus, in the present study we tried to investigate the antiviral activity of AT1001, along with five derivatives, by cell-based assays. Our results provide with the identification of AT1001 peptide molecular framework for lead optimization step to develop new generations of antiviral agents of SARS-CoV-2 with an improved biological activity, expanding the chance for success in clinical trials."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

AT1001 for the Treatment of COVID-19 Related MIS-C (clinicaltrials.gov) - P2a; N=20; Not yet recruiting; Sponsor: Massachusetts General Hospital

Clinical • New P2a trial • Infectious Disease • Novel Coronavirus Disease • CRP • IL6

Current pharmacological approaches and potential future therapies for Celiac disease. (PubMed, Eur J Pharmacol) - "Two of the further advanced clinical trials include AT-1001 Larazotide acetate and IMGX-003 (formerly known as ALV003) Latiglutenase therapies. AT-1001 aims to close the villi's tight junctions, while IMGX-003 acts as a gluten endopeptidase that degrades gluten before being absorbed in the small intestine. This review article summarizes the various preclinical research and clinical trials being conducted and specifies the mechanism by which these drugs function."

Journal • Review • Celiac Disease • Fatigue • Immunology • Inflammation

Larazotide Acetate for Treatment of Celiac Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Clin Res Hepatol Gastroenterol) - "AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings."

Journal • Retrospective data • Review • Celiac Disease • Gastrointestinal Disorder • Immunology

The naturally occurring radioactivity of 'scalar energy' pendants and concomitant radiation risk. (PubMed, PLoS One) - "Metallic pendants code MP15 were found to contain the greatest activity, at 7043 ± 471 Bq from 232Th, while glass pendants code GP11 were presented the greatest 238U and 40K activity, at 1001 ± 172 and 687 ± 130 Bq respectively. MP15 pendants offered the greatest percentage concentrations of Th, Ce, U and Zr, with means of 25.6 ± 0.06, 5.6 ± 0.005, 1.03 ± 0.04 and 28.5 ± 0.08 respectively, giving rise to an effective dose of 2.8 mSv for a nominal wearing period of 2000 h. Accordingly, these products can give rise to annual doses in excess of the public limit of 1 mSv."

Journal

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. (PubMed, J Clin Invest) - "These mechanistic data of MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19-related disease in children."

Clinical • Journal • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions. (PubMed, PLoS One) - "We conclude that LA stimulates repair of ischemic-injured epithelium at the level of the tight junctions, at an optimal dose of 1 μM LA. Higher doses were less effective because of inhibition by LA fragments, which could be subverted by chirally-modifying the molecule, or microdosing LA."

Journal • Preclinical • Celiac Disease • Immunology • CLDN4

A Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variants and Severe Renal Impairment (clinicaltrials.gov) - P3; N=12; Not yet recruiting; Sponsor: Amicus Therapeutics; Trial completion date: Dec 2021 ➔ Dec 2025; Trial primary completion date: Dec 2021 ➔ Dec 2024

Clinical • Trial completion date • Trial primary completion date • Fabry Disease • Genetic Disorders • Renal Disease