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Hep C Vax Flops Among Injection Drug Users in Phase I/II Trial

WASHINGTON — There was a silver lining to a prophylactic vaccine against hepatitis C virus (HCV) that failed to prevent chronic HCV infection: it proved that testing vaccines in a population of patients who inject drugs is possible, a researcher said here.

A phase I/II randomized trial found no effect on 6-month chronic HCV outcome among participants randomized to receive HCV vaccine or placebo (vaccine efficacy -0.529, 95% CI -2.535 to 0.339), reported Andrea Cox, MD, of Johns Hopkins University in Baltimore.

But the vaccine was well-tolerated, and produced an immunogenic response in 78% of vaccine recipients (who responded to vaccine peptide pools in IFN-γ ELISpot assay, which measures T cell response), she reported in a late-breaking presentation at the IDWeek meeting, with joint sponsorship by the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the Society for Healthcare Epidemiology of America (SHEA), and the HIV Medicine Association.

Cox painted a dire picture of the global HCV epidemic worldwide, saying that the chronic rate of both HCV and hepatitis B virus (HBV) infection is rising.

“If the trend continues as predicted, by 2040, [it is] estimated that the mortality from HCV and HBV will exceed that of [tuberculosis], HIV, and malaria combined,” she said.

The World Health Organization is targeting HCV for elimination by 2030, but significant barriers remain, Cox noted. She added that there are 1.5 million new annual infections globally and the rising rate of incident infections in the U.S., whereas HBV, a vaccine-preventable illness, has not shown similar increases.

This vaccine was designed to generate T cell immunity based on viral vectors, and was comprised of recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV, the authors said.

Participants included adults (ages 18-45) who inject drugs at high risk of HCV, but who were not infected with HCV at screening. They were counseled and referred to drug treatment and needle syringe programs, Cox said. Overall, 455 participants received two injections at 0 and 8 weeks of either vaccine or placebo. Their immune response was assessed and they were tested for HCV RNA to measure incident infection. They were followed for 20 months or 9 months following acquisition of infection.

But the result was the same as it has been for the past 30 years for people who have been trying to develop a vaccine against HCV, said Douglas Dieterich, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

“The positive is they were able to prove you can do a study in this population of IV drug users at risk for hepatitis C. The bad news is they haven’t figured out what would work yet. Hepatitis C is a smart virus,” he told MedPage Today.

Dieterich, who was not involved in the study, characterized the study as “a valiant effort, and proof of principle for drug users at high risk.”

Patients were 78% men, 61% white, and were well-balanced in gender, race/ethnicity; ILB28 status, age, and BMI were similar in both groups.

The overall incidence of infection was 13 infections per 100 person years, but there was no difference in incident infection between groups. For immunogenicity, peak response in the vaccine group was 7 days following administration of the boost vaccine.

“T-cell responses were induced, but they were less robust and less broad than in healthy volunteers,” Cox said. “It’s unknown if the vaccine response is targeting the infecting viruses, but that’s something we’re now determining.”

Examining safety, there were 79 serious adverse events reported for 65 participants (12%), but none were related to the vaccine regimen, Cox said. They included endocarditis, trauma, and overdose, which is to be expected in this population. The most common adverse events in the vaccine group were tenderness, pain and erythema, or superficial reddening of the skin. But less than 1% of vaccinated participants experienced severe reactions, including high-grade local reactions, the authors said.

Cox emphasized that the need for a vaccine is critical to interrupt HCV transmission, is significant, and critical to achieve HCV elimination goals.

“Testing vaccines in [people who inject drugs] is possible, but additional strategies will need to be considered, ideally with information gained from this vaccine in informing future vaccine design,” she said.

The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID).

Page and Cox disclosed no relevant relationships with industry. Co-authors disclosed support from Gilead and employment with GlaxoSmithKline and ReiThera.