Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial)

ContextCurrent drugs for chronic hepatitis B therapy have a poor efficacy in terms of post-treatment sustained viral suppression and generate important side effects during and after therapy. Therapeutic vaccination with HBV antigens is an attractive alternative to test.ObjectiveEvaluating the efficacy of a therapeutic vaccine candidate (designated NASVAC) containing both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) versus pegylated interferon (Peg-IFN) in naïve chronic hepatitis B patients.Design, setting, participantsAn open phase III, randomised and treatment controlled clinical trial was conducted in a total of 160 CHB patients, allocated into two groups of 80 patients each to receive NASVAC or Peg-IFN. The vaccine formulation comprised 100 μg of each HBsAg and HBcAg, and was administered in 2 cycles of 5 doses. The control group received 48 subcutaneous injections of Peg-IFN alfa 2b, 180 μg per dose, every week, for 48 consecutive weeks.Main outcome measureThe primary outcome measure was in relation with the proportion of patients showing reduction of the viral load under the limit of detection (250 copies/mL) after 24 weeks of treatment completion.ResultsSustained control of HBV DNA was significantly more common in NASVAC group (pConclusionNasvac induced a superior reduction of the viral load under the limit of detection compared to Peg-IFN treatment. It is a safe and efficacious finite alternative of antiviral treatment for CHB patients.Trial registrationClinicalTrials.gov NCT 01374308.

研究背景：当前慢性乙型肝炎治疗药物在停药后持续病毒抑制方面疗效欠佳，且治疗期间及治疗后会引发显著不良反应。采用乙型肝炎病毒（hepatitis B virus, HBV）抗原开展治疗性疫苗接种，是极具吸引力的备选研究方向。
研究目的：评估同时包含乙型肝炎表面抗原（hepatitis B surface antigen, HBsAg）与乙型肝炎核心抗原（hepatitis B core antigen, HBcAg）的治疗性候选疫苗（命名为NASVAC），相较于聚乙二醇干扰素（pegylated interferon, Peg-IFN）在初治慢性乙型肝炎患者中的治疗疗效。
研究设计、研究场景与研究对象：本研究为开放标签Ⅲ期随机对照临床试验，共纳入160例慢性乙型肝炎（chronic hepatitis B, CHB）患者，按1:1比例随机分为两组，每组各80例，分别接受NASVAC或Peg-IFN治疗。该疫苗制剂每剂含100μg HBsAg与100μg HBcAg，采用2个疗程、每个疗程5剂的方案给药。对照组接受48周连续每周皮下注射聚乙二醇干扰素α2b（Peg-IFN alfa 2b），每次剂量为180μg，总计给药48次。
主要疗效指标：主要疗效终点为治疗结束后24周时，病毒载量降至检测下限（250拷贝/mL）以下的患者占比。
研究结果：现有研究结果显示，NASVAC组患者的HBV DNA持续控制率显著高于对照组（p[原文此处未完整给出]）。
研究结论：与聚乙二醇干扰素治疗相比，NASVAC可使更多患者的病毒载量降至检测下限以下，实现更优的病毒载量抑制效果。其为慢性乙型肝炎患者提供了一种安全有效、疗程有限的抗病毒治疗备选方案。
临床试验注册：ClinicalTrials.gov NCT 01374308。