The phase 1/2 trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population of in people who inject drugs.
According to the US Centers for Disease Control and Prevention (CDC), an estimated 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. During 2017, a total of 3186 cases of acute HCV were reported, but after adjusting for under-ascertainment and under-reporting, the CDC indicates that an estimated 44,300 acute HCV cases occurred in 2017.
For some individuals, HCV infection is a short-term illness, but for 70%-80% of individuals who become infected with HCV, it becomes a long-term, chronic condition. Therefore, it is critical to develop a safe and effective vaccine to prevent chronic HCV infections.
In a late breaker oral abstract at IDWeek 2019, a study team presented their findings from a randomized, double-blind, placebo-controlled, efficacy trial of a chronic HCV vaccine candidate conducted in an at-risk population.
In the multicenter study, the investigators evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both of which were encoded for nonstructural proteins of HCV. The investigators enrolled adults aged 18 to 45 years who were not infected with HCV, but at an increased risk for the infection due to injection drug use.
Participants were randomized to receive either the prime-boost regimen or placebo at days 0 and 56 and were monitored for reactogenicity, adverse events and HCV viremia. The investigators also assessed the vaccine safety, immunogenicity, and efficacy in preventing against progression to chronic HCV infections.
The study enrolled a total of 455 participants into the according-to-protocol efficacy cohort, 202 of whom were in the prime-boost regimen arm and 199 of which were in the placebo arm.
According to the results, the overall incidence was 14.1 infections per 100 person-years. No differences in the development of chronic HCV infection was observed between the vaccine and placebo groups, with 14 chronically infected participants in each group. The efficacy of the vaccine in preventing chronic infection was -0.53 (95% confidence interval [CI], -2.5 to 0.34).
Among the vaccinated individuals, 78% were reported to generate T cell responses to ≥1 vaccine-encoded HCV antigens. The investigators write that the vaccine was generally safe and well tolerated with no serious vaccine-related adverse events.
However, there were more solicited reports of adverse events after either injection in the vaccine group (81%) than in the placebo group (59%), with the difference mainly due to injection-site reactions. The investigators note that serious adverse events and deaths occurred with similar frequencies across the 2 groups.
“A randomized, placebo controlled, phase 1/2 trial of a prime-boost vaccine to prevent chronic HCV infection was completed in an at-risk population, demonstrating the feasibility of conducting rigorous vaccine research in people who inject drugs,” the authors conclude. “The regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection.”
The abstract, A Randomized, Double-Blind, Placebo-Controlled Efficacy Trial of a Vaccine to Prevent Chronic Hepatitis C Virus Infection in an at-Risk Population, was presented in a late breaker session on Friday, October 4, 2019, at IDWeek 2019 in Washington, DC.