Efficacy and Safety of a Nanoparticle Therapeutic Vaccine in Patients with Chronic Hepatitis B: A Randomized Clinical Trial.

BACKGROUND & AIM HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, ePA-44, for CHB. APPROACH & RESULTS A two-stage phase II trial, which included a 76-week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68-week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov number, NCT00869778). In stage 1, 360 HLA-A2-positive and HBeAg-positive patients were randomly and equally distributed to receive six subcutaneous injections of 600 µg or 900 µg ePA-44 or placebo at week 0, 4, 8, 12, 20, and 28. In stage 2, 183 patients received extended 900 µg ePA-44 and 26 patients were observed for relapse without further treatment. The primary endpoint was the percentage of patients with HBeAg seroconversion at week 76. At week 76, patients receiving 900 µg ePA-44 achieved significantly higher HBeAg seroconversion rate (38.8%) vs. placebo (20.2%) (95% CI, 6.9-29.6%; P=0.002). With a combined endpoint of HBeAg seroconversion, ALT normalization and HBV DNA <2000 IU/mL, both 900 µg (18.1%) and 600 µg (14.3%) resulted in significantly higher rate vs. placebo (5.0%) (P=0.002 and P=0.02, respectively) at week 76. In stage 2, none (0/20) of 900 µg ePA-44 treated patients experienced serologic relapse. The safety profile of ePA-44 was comparable to that of placebo. CONCLUSIONS Among progressive CHB patients with HLA-A2-positive, a finite duration of 900 µg ePA-44 monotherapy resulted in significantly higher HBeAg seroconversion rate than placebo and sustained off-treatment effect. A phase III trial is ongoing (ChiCTR2100043708).