So Far, So Good for Chikungunya Vaccine in Phase III Trial

A live-attenuated vaccine against mosquito-borne chikungunya virus was highly immunogenic across age groups, with no serious safety concerns, a researcher said.

Topline results from the phase III trial of VLA 1553, a live-attenuated vaccine against chikungunya virus (CHIKV), had a 98.5% (95% CI 96.2-99.2) seroprotection rate, significantly exceeding the FDA's requirement of 70% for licensure, reported Juan-Carlos Jaramillo, MD, chief medical officer for Valneva in Saint-Herblain, France.

Moreover, the vaccine candidate exhibited a 64-fold increase in neutralizing antibody titers in 257 of 268 participants (95.9%) at day 29, and exhibited comparable results across age ranges.

VLA-1553 was also well-tolerated, and most adverse events (AEs) were mild or moderate, Jaramillo said in a presentation at the American Society of Tropical Medicine & Hygiene (ASTMH) virtual meeting.

There is no FDA-approved vaccine to protect against chikungunya, which is primarily seen in the Americas, parts of Africa, and southeast Asia. While the mortality rate is low, the morbidity rate is high, with four out of five people infected experiencing chronic arthralgia, Jaramillo said. There is also no cure, and the only treatment is supportive care.

"As global warming becomes more prevalent, there is an expanded geographic distribution" of chikungunya, he added, warning of "case importation and local disease transmission from travelers to affected areas."

VLA-1553 showed promise in challenge models in non-human primates, Jaramillo said, where immunization "demonstrated protection against viremia and disease" in the animals.

This phase III trial is ongoing. In total, 4,115 U.S. adults, ages 18 and up, were randomized to receive either one dose of VLA-1553 or placebo. The primary endpoint was the proportion of patients with seropositive CHIKV neutralizing antibody titers 28 days after vaccination. The seroprotective titer was a "surrogate of protection agreed upon with the FDA to support licensure via accelerated approval pathway," Jaramillo said.

Solicited AEs were captured for 10 days following vaccination, and recruitment was stratified by age: 3,652 adults ages 18-64 and 463 adults ages 65 and up.

Overall, 3,082 adults were randomized to the vaccine group and 1,033 were randomized to placebo. Participants were a mean age of 45 at screening, 55% were women, and 80% were white. All participants were seronegative at baseline.

Jaramillo noted that the immunogenicity subset was the first 500 participants enrolled at selected sites.

Of note, protective CHIKV neutralizing antibody titers were reported in 99% of older adults at day 28, he said, calling the data "robust."

"The compelling immunogenicity profile from the phase I trial was confirmed," Jaramillo added.

Examining safety, most AEs resolved within 3 days, with 1.6% of participants reporting severe solicited AEs. About half of participants had solicited systemic AEs, with headache as the most common. About 15% of participants reported solicited local AEs, with tenderness as the most common.

There were 11 AEs of special interest, including 10 participants in the vaccine group. There were two related serious AEs, which are still undergoing continued review. Three participants had "severe fever."

About 9% of participants reported unsolicited treatment-related AEs, with the most frequent being chills and transient neutropenia.

A final safety analysis is expected following 6 months of follow-up, Jaramillo said.

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