闻玉梅YIC 第三阶段的临床试验结果

StephenW

Results of a Phase III Clinical Trial with an HBsAg-HBIG Immunogenic Complex Therapeutic Vaccine for Chronic Hepatitis B Patients: Experiences and Findings

    Dao-Zhen Xua,
    Xuan-Yi Wangb,
    Xin-Liang Shenc,
    Guo-Zhong Gongd,
    Hong Rene,
    Li-Min Guoa,
    Ai-Min Sunf,
    Min Xug,
    Lan-Juan Lih,
    Xin-Hui Guoi,
    Zhen Zhenj,
    Hui-Fen Wangk,
    Huan-Yu Gongl,
    Cheng Xum,
    Nan Jiangn,
    Chen Pano,
    Zuo-Jiong Gongp,
    Ji-Ming Zhangq,
    Jia Shangr,
    Jie Xus,
    Qing Xiet,
    Tie-Feng Wuu,
    Wen-Xiang Huangv,
    Yong-Guo Liw,
    Jing Xuc,
    Zheng-Hong Yuanb,
    Bin Wangb,
    Kai Zhaoc,
    Yu-Mei Wenb, Corresponding author contact information, E-mail the corresponding author, E-mail the corresponding author,
    for the
        YIC Efficacy Trial Study Team

    a Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China
    b Key Laboratory Medical molecular Virology, MoE/MoH, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China
    c National Vaccine & Serum Institute, Beijing, People’s Republic of China
    d The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China
    e The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
    f The Institute of Medical Sciences, Henan, Zhengzhou, People’s Republic of China
    g Guangzhou Eight People’s Hospital, Guangzhou, People’s Republic of China
    h The First Affiliated Hospital, Medical School of Zhejiang University, Hanzhou, People’s Republic of China
    i Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China
    j Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China
    k Beijing 302 Hospital, Beijing, People’s Republic of China
    l The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China
    m Shenzhen Donghu Hospital, Shenzheng, People’s Republic of China
    n People’s Hospital of Sichuan Province, Chengdu, People’s Republic of China
    o Fuzhou Infectious Disease Hospital, Fuzhou, People’s Republic of China
    p People’s Hospital, Wuhan University, Wuhan, People’s Republic of China
    q Huashan Hospital, Fudan University, Shanghai, People’s Republic of China
    r Henan Provincial People’s Hospital, Zhenzhou, People’s Republic of China
    s The Third People’s Hospital, Jiaotong University, Shanghai, People’s Republic of China
    t Ruijin Hospital, Jiaotong University, Shanghai, People’s Republic of China
    u Hangzhou Sixth People’s Hospital, Hanzhou, People’s Republic of China
    v The First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
    w The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China

    http://dx.doi.org/10.1016/j.jhep.2013.05.003, How to Cite or Link Using DOI

   

Abstract
Background and Aims

Though, various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind placebo controlled phase II B clinical trial of YIC has been reported previously, and herein results of phase III clinical trial among 450 patients are presented.
Methods

Twelve doses of either YIC or alum alone as the placebo was administrated randomly to 450 CHB patients and followed for 24 weeks after the completion of immunization. The primary endpoint was HBeAg seroconversion, and the secondary endpoints were decrease in viral load, improvement of liver function and histology.
Results

In contrast to previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in decrease of HBeAg seroconversion rate from 21.8% to 14.0% in YIC group, but increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05).
Conclusions

Over stimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. Appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation。
Funding

Supported by China National Science and Technology Major Project (grant No.: 2008ZX10002-003)

StephenW

背景和目的

虽然，各种实验性的治疗方法对慢性B型肝炎感染已有报道，少数已通过临床试验验证。我们已经开发出抗原抗体（乙肝表面抗原，乙肝免疫球蛋白）免疫原性复杂的治疗性疫苗候选明矾佐剂（YIC），旨在打破乙肝免疫耐受，通过调节病毒抗原处理和演示。一项双盲安慰剂对照的临床试验阶段II B YIC已先前报道，本文在450名患者的III期临床试验的结果。
方法

12剂量的任YIC或明矾单独给药安慰剂随机对450例慢性乙型肝炎患者免疫完成后，其次为24周。主要终点为HBeAg血清学转换，病毒载量下降，改善肝功能和组织学和次要终点。
结果

YIC或明矾注射相反前一阶段II B YIC六剂和明矾作为安慰剂的试验，导致YIC组从21.8％至14.0％，HBeAg血清学转换率下降，但是从9％上升至21.9％中的明矾小组。血清中HBV DNA和肝功能正常化，减少在两组相似（P> 0.05）。
结论

过度刺激YIC没有增加，反而降低其疗效由于疲劳主机免疫。应探索适当的免疫方案和治疗性疫苗是至关重要的。多个单独明矾注射可能已经刺激了强有力的炎症和先天免疫反应，有助于其疗效，需要进一步调查。

姑苏旅伴

StephenW 发表于 2013-5-15 19:55
Results of a Phase III Clinical Trial with an HBsAg-HBIG Immunogenic Complex Therapeutic Vaccine for ...

“Results
In contrast to previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in decrease of HBeAg seroconversion rate from 21.8% to 14.0% in YIC group, but increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05).”

这是个什么结果呀？看上去对照组(明矾)的效果比治疗组(YIC)要好啊！(21.9％ vs 14.0％)

StephenW

回复 姑苏旅伴 的帖子

Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation。

需要进一步调查

姑苏旅伴

回复 StephenW 的帖子

看来，那治疗性疫苗希望渺茫啊！

StephenW

回复 姑苏旅伴 的帖子

需要进一步研究

姑苏旅伴

StephenW 发表于 2013-5-15 21:46
回复 姑苏旅伴 的帖子

Multiple injections of alum alone could have stimulated potent inflammatory an ...

“Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation。”

我猜想您我都写过科研论文吧。上面的那段话难道不是用来对negative results作自我解脱的经典话语吗？

MP4

姑苏旅伴 发表于 2013-5-15 23:32
“Multiple injections of alum alone could have stimulated potent inflammatory and innate immune re ...

结果打了还反作用，哈哈，以后要多吃明矾油条么?

http://www.chictr.org/cn/proj/show.aspx?proj=1681

还在临床试验ING，淡定。

MP4

姑苏旅伴 发表于 2013-5-15 20:44
“Results
In contrast to previous phase II B trial using six doses of YIC and alum as placebo, six ...

氢氧化铝组吧。

MP4

姑苏旅伴 发表于 2013-5-15 21:49
回复 StephenW 的帖子

看来，那治疗性疫苗希望渺茫啊！

http://www.ihepa.com/ArticleViewf.aspx?id=5513

如在中国由闻玉梅教授开展的基于抗原和抗体组合的原创方法的临床III期试验，目前正在分析结果，获得了些令人鼓舞的结果，因为这种疫苗的有效性与干扰素相似但要便宜很多，但是比预期的效果还是差些。因此我们需要一步一步地发展。从每一个试验中汲取经验，即使是阴性结果，这样我们可以在下一步提高。