MALMO, SWEDEN – in an interim analysis of an ongoing phase 2 study, Taisei Masuda, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
The randomized, double-blind, multinational trial remains blinded because follow-up is continuing, so – to the disappointment of the ESPID audience – there are as yet no data on duration of antibody persistence or clinical efficacy.
However, an earlier phase 2 study in 420 healthy participants aged 18-64 years showed that the Takeda vaccine elicited persistent immune responses 1 year post vaccination and that higher antibody levels correlated with a reduced frequency of moderate to severe vomiting and diarrheal illness following oral challenge with norovirus (). Follow-up will continue in order to learn how long the protective immune response lasts in adults, according to Dr. Masuda, of Takeda Pharmaceuticals in Zurich.
The bivalent Takeda vaccine is the first candidate vaccine to reach the randomized trial stage. An oral vaccine in tablet form under development by Vaxart, a San Francisco Bay Area biotech company, recently completed preliminary phase 1 studies.
Dr. Masuda explained that the Takeda vaccine contains virus-like particle antigens from norovirus strains GI.1 and GII.4c, which together account for the majority of human norovirus illness. These virus-like particles are formed on the outer surface of the virus. Of note, virus-like particle–based vaccines against hepatitis B and human papillomavirus have won regulatory approval in the United States, Europe, and elsewhere.
He presented data on 120 healthy subjects aged 1 year to less than 4 years old and another 120 aged 4 years to less than 9 years. They are part of a larger phase 2 study of 840 children as young as age 6 weeks. This was a dose-finding study, so participants received various doses of the vaccine on day 1 and either a second dose or a saline injection 28 days later. The vaccine, which contains aluminum hydroxide to enhance immunogenicity, comes in prefilled syringes.
At 57 days of follow-up in this interim analysis, protective seroresponse rates as defined by at least a fourfold increase in histo-blood group antigen–blocking titers approached 100%. In the older group, this was typically achieved with a single dose of vaccine. However, the younger group of children generally derived further benefit from a second dose, according to Dr. Masuda.
In terms of safety concerns, he said no serious adverse events occurred in the study and no one withdrew from the trial because of vaccine-related side effects. The overall safety picture was the same in the two age groups. The incidence of fever of 38° C or higher was similar after administration of vaccine and placebo. Injection site pain occurred in one-quarter of younger vaccine recipients, in 38%-63% of those aged 4 years or older, and in 17%-22% who got placebo injections. Those and other local and systemic adverse events were mostly mild and transient. Their incidence and severity weren’t related to vaccine dosage.