Larazotide safe, could improve MISC symptoms as adjuvant therapy | Image Credit: © Bernard Chantal - © Bernard Chantal - stock.adobe.com.

An oral drug initially developed to treat Celiac disease may help children recover more quickly from multisystem inflammatory syndrome in children (MIS-C), according to a randomized trial published in Science Translational Medicine.¹

Larazotide, a zonulin antagonist, was tested in 12 hospitalized children with MIS-C, a rare but serious inflammatory condition that occurs in some pediatric patients following SARS-CoV-2 infection. In the phase 2a, double-blind, placebo-controlled study, patients received either larazotide or placebo 4 times daily for 3 weeks and were followed for 24 weeks. The median age of participants was 5.7 years.

The therapy was well tolerated, with no larazotide-related adverse events reported. The drug was associated with faster clearance of SARS-CoV-2 spike antigen from circulation, quicker resolution of gastrointestinal symptoms, and an accelerated return to usual activities.

Larazotide is designed to strengthen intestinal barriers, limiting the translocation of viral particles from the gut into the bloodstream. Researchers hypothesized that reducing this translocation might dampen the hyperinflammatory response seen in MIS-C and improve recovery.

According to study results, spike protein concentrations correlated with inflammation markers such as interferon-γ (P = 0.004) and interleukin-6 (P < 0.0001), and with gastrointestinal symptoms as assessed by the PedsQL GI symptom score (P = 0.003).

Early signals of therapeutic potential

In a statement released by Mass General Brigham, lead study author Lael Yonker, MD, emphasized the broader implications of the findings.²

“While our study is small, its results are powerful and have implications not only for MIS-C, but potentially for long COVID,” said Yonker, co-director of the Cystic Fibrosis Center and Pulmonary Genetics Clinic at Mass General Brigham for Children. “Our findings suggest that larazotide is safe and quickly resolves symptoms in children with MIS-C. We are now running a clinical trial to test whether larazotide may also be a useful therapy to treat patients with long COVID.”²

Current treatment strategies for MIS-C primarily involve anti-inflammatory medications, such as intravenous immunoglobulin or corticosteroids. However, some children experience a relapse of symptoms after initial treatment, as these drugs, according to Mass General Brigham, are not designed to target the "sticky SARS-CoV-2 viral particles that may persist in the gut."

“Larazotide strengthens intestinal barriers to limit the number of materials—like SARS-CoV-2 viral particles—that exit the intestines and enter circulation,” the press release stated.

Study design and next steps

The clinical trial was funded in part by the National Institutes of Health and monitored children for 6 months after enrollment.² The findings offer preliminary evidence of a targeted gut-based approach in treating MIS-C.¹

Larazotide's mechanism of action, focused on reducing zonulin-mediated gut permeability, may have relevance beyond MIS-C, as viral antigen persistence in the gastrointestinal tract is increasingly being explored in long COVID.

The trial’s outcomes demonstrate larazotide may be a safe and promising treatment option for children with MIS-C.

References:

1. Yonker LM, Kane AS, Swank Z, et al. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. Sci. Transl. Med. doi:10.1126/scitranslmed.adu4284
2. Clinial trial finds safe, effective treatment for children with severe post-COVID syndrome. Mass General Brigham. Press release. July 30, 2025. Accessed July 30, 2025.