- In most cases of multisystem inflammatory syndrome in children, a rare condition that can occur after a COVID infection, kids present with gastrointestinal symptoms.
- In this small placebo-controlled trial, the proportion of patients who achieved gastrointestinal symptom recovery at days 7 and 14 was significantly greater with larazotide.
- The novel drug may help prevent inflammatory spike protein antigens from escaping the gastrointestinal tract and reaching the bloodstream.
Adding a novel oral drug originally designed to treat celiac disease to standard treatment for post-COVID multisystem inflammatory syndrome in children (MIS-C) appeared safe and effective in a small, phase IIa randomized, double-blind trial.
Among 11 patients with MIS-C, a larger proportion of those randomized to larazotide achieved 90% or greater gastrointestinal symptom recovery compared with placebo at days 7 and 14 of treatment (67% vs 20% at each time point; P<0.0001 for both), with no difference at day 21, reported Lael Yonker, MD, of Massachusetts General Hospital in Boston, and colleagues.
A significantly larger proportion of children taking the zonulin antagonist also cleared spike protein antigen at 7, 14, and 21 days, and none of the children receiving larazotide had detectable spike protein antigen by day 21 of treatment. Significantly more of the larazotide-treated children were back to their usual activities at day 14 and day 21 than those on placebo, the study authors noted in Science Translational Medicine.
“We show that larazotide serves as a beneficial adjuvant in the treatment of MIS-C, and it may also prove beneficial for treating long COVID and other post-acute sequelae of COVID-19 [PASC] presentations as well,” the researchers wrote.
MIS-C is a rare condition that can occur after a COVID infection in children and that presents with a combination of gastrointestinal symptoms, high fever, or life-threatening cardiac injury. Recent estimates show that cases are still occurring but at a much lower rate than early in the pandemic.
Most MIS-C patients present with gastrointestinal symptoms. Larazotide inhibits gut epithelial cells’ zonulin receptor, which in turn helps prevent damage to the gut epithelial barrier, Yonker and colleagues explained. An intact barrier stops the escape of inflammatory spike protein antigens from the gastrointestinal tract into the bloodstream.
“Lots of researchers have shown that there are viral reservoirs after someone has COVID-19, and definitely in the gut,” Yonker told MedPage Today. “Our hope is that we can use larazotide to block the leak of spike protein antigen from the gut and contain it there. If we can get the antigen out of the blood, maybe that can help people recover faster.”
The researchers randomized 12 children ages 1 month to 21 years with current or recent SARS-CoV-2 infection and MIS-C to either oral larazotide or placebo four times daily for 21 days in addition to standard MIS-C treatment, which includes corticosteroids, intravenous immunoglobulin, or anakinra (Kineret).
Patients weighing less than 25 kg received 0.25 mg of larazotide, while those 25 kg or more received 0.5 mg of larazotide. Safety follow-up continued for 168 days. One patient in the placebo group did not complete dosing (and was not included in the efficacy analysis) while a patient who received larazotide was lost to follow-up at 16 weeks.
The median age for the entire cohort was 5.7 years and two-thirds of the patients were male.
The larazotide and placebo group had similar rates of mild and moderate adverse events, and none of the patients had a severe adverse event.
Study limitations included enrolling fewer study participants than planned, driven by rising vaccination rates and a subsequent steep drop in MIS-C cases during the study. The researchers had planned on up to 20 patients, but having only 12 made it possible that intrinsic differences between the two groups, rather than drug effect, contributed to the findings.
Yonker and her colleagues are now enrolling children and adults in a larger phase II trial to assess larazotide’s safety and effectiveness in people with long COVID symptoms.
Disclosures
The study was supported by the Chleck Foundation, the European Biomedical Research Institute of Salerno, and the National Heart, Lung, and Blood Institute.
Yonker is a co-inventor on a patent for zonulin antagonists to treat MIS-C, as are two other co-authors. Co-authors also disclosed relationships with Alba Therapeutics, Mead Johnson Nutrition, and Quanterix.
Primary Source
Science Translational Medicine
Source Reference: Yonker LM, et al “Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide” Sci Transl Med 2025; DOI: 10.1126/scitranslmed.adu4284.
