Dataset Information

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.

ABSTRACT:

Background

A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease.

Methods

In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months.

Results

A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×10³ IU per milliliter and 1804.93×10³ IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups.

Conclusions

In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).

SUBMITTER: Page K

PROVIDER: S-EPMC8367093 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Background The development of a safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of elimination efforts, providing the rationale for the first HCV vaccine efficacy trial. Methods In a randomized, multicenter, double-blind, placebo-controlled efficacy trial (NCT01436357), we evaluated a recombinant chimpanzee adenovirus 3 vector vaccine prime followed by a recombinant modified vaccinia Ankara boost, both encoding nonstructural proteins of HCV. HCV-uninfected adults 18–45 years old at-risk for HCV infection due to injection drug use were randomized to receive the prime-boost regimen or placebo at Days 0 and 56. Trial participants were monitored for vaccine reactogenicity, adverse events, and HCV viremia. Vaccine safety, immunogenicity, and efficacy against progression to chronic HCV infection were assessed. Results A total of 455 subjects received the prime-boost regimen or two doses of placebo, with 202 and 199 in the respective groups included in the according-to-protocol efficacy cohort. Overall incidence of infection was 14.1 infections per 100 person-years. There were no differences in development of chronic infection between vaccine and placebo arms, with 14 chronically infected subjects in each group. Specifically, the vaccine efficacy in preventing chronic infection was ?0.53 (95% confidence interval [CI], ?2.5 to 0.34). Of vaccinated subjects, 78% generated T-cell responses to ?1 vaccine-encoded HCV antigens. The vaccine was generally safe and well tolerated with no serious vaccine-related adverse events. 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. Serious adverse events and deaths occurred with similar frequencies in the two groups. Conclusion A randomized, placebo controlled, Phase I/II 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 regimen elicited robust immune responses without evident safety concerns, but did not provide protection against chronic HCV infection. Disclosures Ventzislav Vassilev, PhD, GlaxoSmithKlein Vaccines (Employee), Lan Lin, MD, GlaxoSmithKlein Vaccines (Employee), Alfredo Nicosia, PhD, ReiThera (Employee, Shareholder), Antonella Folgori, PhD, ReiThera (Employee), ReiThera (Employee, Shareholder. Other Authors: No reported disclosures.