NCT05747534

AT1001 for the Treatment of Long COVID

Phase 2a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Larazotide (AT1001) for the Treatment of Long COVID in Children and Adults

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 7 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study is to evaluate the safety and efficacy of Larazotide (AT1001) versus placebo in children and adults 7 to ≤50 years of age who present with symptoms of Long COVID in the presence of SARS-CoV-2 antigenemia. AT1001 (n=100) or placebo (n=50) will be administered orally four times a day (QID) for 21 days.

Detailed description

This is a Phase 2a randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of AT1001 for use in children and adults with symptoms of Long COVID. Eligible participants (N= 150) will be treated with AT1001 (n= 100) or matching placebo (n= 50) orally four times a day (QID for 21 days). The study will consist of two phases: I. Baseline Visit and Treatment phase After confirming subject eligibility, a licensed physician investigator will obtain informed consent. Subjects will be asked to complete baseline surveys (SBQ™-LC, PedsQL, and Symptom Severity Survey) to assess organ involvement and symptom severity. A venous blood sample will be obtained to, among other things, assess for SARS COV-2 antigenemia (such as Spike protein) and obtain a comprehensive metabolic panel and liver function test. Patients who meet inclusion criteria will be treated with AT1001 or matching placebo at a dose of 250 μg or 500 μg for 21 days. Drug dose will be determined by weight: patients \<25.0 kg will receive 250 μg of Larazotide or Placebo, and patients ≥25.0 kg will receive 500 μg of Larazotide or Placebo. Randomization and initial dosing will occur on Visit 1 (Day 1). Visits will then occur on a weekly basis during the treatment phase and will consist of data and/or specimen collection. Visit 2 (Week 1) and Visit 3 (Week 2) will take place virtually and will not involve sample collection. Once the subject has completed 21 days of dosing, Visit 4 (Week 3) will take place in person and require the collection of blood, stool and nasal swabs. II. Follow-up phase Patients will have two additional virtual follow-up visits after completing their 21-day course of treatment with the study drug. The first follow up visit will occur one week after completing the study drug (ie. at week 4), and the second will occur one month later (ie. at week 8). Week 8 visit will serve as the end of study visit. Biospecimens will not be collected during the follow-up phase. Safety monitoring, including physical examination, vitals, and clinical laboratory testing will be performed during the baseline phase and after completion of treatment. Adverse events and concomitant medications will be recorded during the entire study. Total duration of the participants' participation in the study is approximately 8 weeks (with 21 days treatment period). Total duration of the study is projected to be roughly 42 months, dependent on enrollment timeline.

Conditions

• Long COVID
• Long COVID-19
• Post Acute COVID-19 Syndrome
• Post Acute Sequelae of COVID-19

Interventions

Type	Name	Description
DRUG	Larazotide Acetate	AT1001 (Larazotide) is a locally acting, non-systemic, octapeptide inhibitor of the zonulin receptor that has shown efficacy in a large variety of animal models of inflammation. The effectiveness of AT1001 in controlling paracellular permeability as a tight junction regulator has been widely demonstrated in animal models both in vitro and in vivo. In MIS-C, prolonged presence of SARS-CoV-2 in the GI tract leads to release of zonulin, a biomarker of intestinal permeability, with subsequent trafficking of SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation (Yonker, et. al. 2021). Five children treated with AT1001 (through an Emergency Investigational New Drug request authorized by the FDA) displayed a decrease in plasma SARS-CoV-2 Spike antigen levels, inflammatory markers, and symptom improvement superior to that achieved with the current standard of treatment for MIS-C (ie. immunoglobulin, systemic steroids) (Yonker, et. al. 2021) (Yonker, et. al. 2022)
DRUG	Placebo	Matching placebo will be administered orally four times a day (QID) to participants in the placebo arm.

Timeline

• Start date: 2023-05-31
• Primary completion: 2026-07-31
• Completion: 2027-03-31
• First posted: 2023-02-28
• Last updated: 2025-07-28

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study