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流浪1216 发表于 2015-12-10 11:39 
有知道什么时候上市吗 它的疗效到底怎么样 能不能达到功能性痊愈
Phase III study of a therapeutic vaccine candidate (NASVAC)
containing the hepatitis B virus core antigen (HBcAg)
and the HBV surface antigen (HBsAg) for treatment of patients
with chronic hepatitis B
Mamun-Al-Mahtab 1, Mohammed Fazle Akbar 2, Julio Ce´sar
Aguilar 3, Vincent Serra 4, Salimur Rahman 1, Pascale Berthillon 5,
Christian Trepo 5, Josianne Nitcheu 4, Pierre Vandepapelie`re 4,
Gerardo Enrique Guillen Nieto 3
1Department of Hepatology, Bangabandhu Sheikh Mujib Medical University,Dhaka,Bangladesh,
2 Toshiba General Hospital, Tokyo,
Japan,
3 Center for Genetic Engineering and Biotechnology, Havana,
Cuba,
4 Wittycell, Evry, France,
5 INSERM 1052/CRCL, Lyon France
Background and aims: Curative therapies for patients with chronic
Hepatitis B (CHB) include pegylated interferon-alpha (pegIFN-a) and
nucleot(s)ide analogues (NUCs). However, pegIFN-a is effective in
approximately one-third of the treated patients only, while the need for
long term treatment is the main limitation of NUCs. Because immune
responses are impaired in patients suffering from CHB, therapeutic
vaccination has become an important strategy to help viral clearance, by
stimulating patients’ hepatitis B specific immune responses. We have
developed a therapeutic vaccine candidate (NASVAC) which is based
on the use of a combination of recombinant HBsAg and HBcAg. We
conducted a phase III clinical study in Bangladesh to evaluate the
clinical efficacy of repeated intranasal/subcutaneous immunizations of
NASVAC to CHB patients to reduce serum HBV DNA levels and to
induce HBsAg/HBeAg clearance or seroconversion.
Methods: One hundred and sixty subjects (of whom 20 % were
HbeAg positive and 80 % HBeAg negative) naı¨ve to anti-HBV
treatment for at least 6 months were randomly assigned to one of the
two following regimens: either NASVAC (100 mcg antigen per
dose), five intranasal (IN) inoculations every 14 days during the first
cycle followed by 5 IN and 5 subcutaneous (SC) inoculations every
14 days during the second cycle of inoculation for a total duration of
24 weeks or weekly SC injections of pegIFN-a for 48 weeks. Patients
in both groups were evaluated over time at week 12, 24, 48, 72 and 96
after beginning of the treatment for serum HBVDNA (quantitative
PCR), ALT, AST, HBeAg, HBsAg, and for safety.
Results: NASVAC was safe and well tolerated inducing reactions
similar to those caused by pegIFN-a but less frequently and less
severe. Both treatments induced a strong and similar antiviral
response during therapy. After cessation of treatment HBV DNA
levels increased again in both groups, but at very different rates. At
week 72 (24 weeks after the end of pegIFN-a treatment and 48 weeks
after the end of NASVAC treatment), the HBV DNA levels were
significantly lower in the NASVAC group than in the pegIFN-a group
(p = 0.03), with almost 80 % of NASVAC treated patients remaining
under 10’000 c/mL. This delayed rebound in the NASVAC group
suggests a sustained antiviral effect as compared to the pegIFN-a
group. Similarly, while at the end of treatment the percentage of
patients with HBeAg loss was similar in both groups (NASVAC 50 %
at week 24; pegIFN-a 55 % at week 48), at week 96 the percentages
in the NASVAC and pegIFN-a groups were 62 and 33 %
respectively. The level of HBsAg in the pegIFN-a group decreased
following treatment until W48, and then increased back to the baseline
levels at W96. However, while no difference in the level of
HBsAg was found from baseline until W72 in the NASVAC group,
the treatment had a significant influence on lowering the HBsAg at
W96 follow-up (p = 0.0074).
Conclusions: The data presented here demonstrate that therapeutic
vaccination with NASVAC has a profound antiviral effect that is
more sustained than pegIFN-a after the end of treatment. This delayed
viral rebound is accompanied by a sustained HBeAg loss. These
results do support further developments to evaluate the therapeutic
potential of NASVAC in endemic regions.
III期研究的治疗性疫苗候选（NASVAC）
含有乙型肝炎病毒核心抗原（HBcAg）
和HBV表面抗原（HBsAg）进行治疗的病人
慢性乙型肝炎
马蒙 - 铝 - Mahtab 1，穆罕默德·阿克巴Fazle 2，胡Ce'sar
阿吉拉尔3，文森特·塞拉4，Salimur拉赫曼1，帕斯卡尔Berthillon 5，
基督教TREPO 5，Josianne Nitcheu 4，皮埃尔Vandepapelie`re 4，
赫拉尔多·恩里克·吉兰涅托3
教研室肝病，Bangabandhu谢赫·穆吉布医科大学，达卡，孟加拉国，
2东芝总医院，东京，
日本，
3中心遗传工程和生物技术，哈瓦那，
古巴，
4 Wittycell，埃夫里，法国，
5 INSERM 1052 / CRCL，法国里昂
背景和目的：疗效的疗法治疗慢性
乙型肝炎（CHB）包括聚乙二醇化的干扰素-α（pegIFN-a）和
nucleot（S）类似物（NUCs）。然而，pegIFN-a是有效
大约三分之一只治疗的患者，而不需
长期治疗是NUCs的主要限制。因为免疫
反应的患者的慢性乙肝，治疗痛苦受损
接种疫苗已成为一个重要的策略，帮助清除病毒，通过
刺激患者的乙型肝炎特异性免疫应答。我们有
开发了一种治疗性的疫苗候选（NASVAC），它是基于
对使用重组HBsAg和HBcAg的的组合。我们
进行了一项III期临床研究在孟加拉国，以评估
反复鼻的临床疗效/皮下免疫接种
NASVAC到CHB患者降低血清HBV DNA水平和
诱导的HBsAg / HBeAg清除或血清学转换。
方法：100名和60名（其中20％为
HBeAg阳性和80％HBeAg阴性），天真的抗乙肝病毒
治疗至少6个月的被随机分配的所述一个
以下两种方案：每要么NASVAC（100微克抗原
剂量），五鼻内（IN）中的第一个接种每14天
周期接着用5 IN和5皮下（SC）接种每
接种的总持续时间在第二周期在14天期间
24周或pegIFN-一个48周的每周SC注射。病人
两组进行了评价随时间在12 96个周，24，48，72和
治疗血清HBVDNA的开始（定量后，
PCR），ALT，AST，e抗原，乙肝表面抗原，并为安全。
结果：NASVAC是安全且耐受性良好诱导反应
类似于致pegIFN-一个但较不频繁和少
严重。引起强烈而类似的抗病毒治疗都
治疗过程中的反应。停止治疗HBV DNA后，
水平两组再次增加，但在非常不同的费率。在
72个周（pegIFN-a治疗和48周结束后24周
NASVAC治疗结束）后，乙型肝炎病毒DNA水平
显著低NASVAC组比pegIFN-一组中的
（p值= 0.03），与NASVAC近80％的患者其余
在10,000 C /毫升。在NASVAC组中的延迟反弹
表明了持续抗病毒效果相比于pegIFN-一个
组。同样，虽然在处理的百分比的端
患者HBeAg消失在两组相似（NASVAC 50％
在第24周; pegIFN-一个在48周）55％，在96周的百分比
在NASVAC和pegIFN-A组分别为62和33％
分别。 HBsAg的pegIFN-一组中的水平降低
下面的治疗，直至W48，然后增加回到基线
水平W96。然而，虽然在水平没有差异
乙肝表面抗原被发现从基线到W72的NASVAC组中，
治疗对降低乙肝表面抗原在显著影响
W96随访（p值= 0.0074）。
结论：这里呈现的数据证明，治疗
接种NASVAC有着深刻的抗病毒效果是
比在治疗结束后pegIFN-更持续。这个延迟
病毒反弹是伴随着持续的HBeAg转阴。这些
结果并支持进一步的发展，以评价治疗
NASVAC在流行地区的潜力。 |
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楼主: StephenW
发表于 2015-12-10 08:41
