隨機臨床試驗：HS-10234與替諾福韋治療慢性乙型肝炎的安全性

StephenW

Randomised clinical trial: safety, efficacy and pharmacokinetics of HS-10234 versus tenofovir for the treatment of chronic hepatitis B infection
Hong Zhang  1 , Yue Hu  1 , Min Wu  1 , Jingrui Liu  1 , Xiaoxue Zhu  1 , Xiaojiao Li  1 , Hong Chen  1 , Cuiyun Li  1 , Chengjiao Liu  1 , Junqi Niu  2 , Yanhua Ding  1
Affiliations
Affiliations

    1
    Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
    2
    Department of Hepatology, The First Hospital of Jilin University, Jilin, China.

    PMID: 33249630 DOI: 10.1111/apt.16196

Abstract

Background: HS-10234 is a novel prodrug of tenofovir developed to increase anti-viral potency and to reduce systemic toxicities.

Aims: To evaluate the tolerability, pharmacokinetics and anti-viral efficacy of HS-10234 in patients with chronic hepatitis B (CHB) infection METHODS: Treatment-naïve subjects with non-cirrhotic CHB were divided into three groups (n = 12/group) and randomised within each group to receive 10, 25 or 40 mg of HS-10234, or 300 mg of tenofovir disoproxil fumarate (TDF) once a day for 28 days.

Results: Among 36 enrolled subjects, 33.3% were hepatitis B e antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.32-7.42 log10 IU/mL. Nephrotoxicity and serious adverse events were not observed; all adverse events were mild or moderate and non-specific. The mean reductions in serum HBV DNA after 28 days were -2.70, -2.89, -2.72 and -3.04 log10 IU/mL for treatment with 10, 25 or 40 mg HS-10234, and 300 mg TDF, respectively. HS-10234 and its metabolite TFV showed linear, dose-proportional pharmacokinetics. The concentrations of active TFV-DP in peripheral blood mononuclear cells were higher (approximately 2- to 11-fold increase) and TFV in plasma were lower (approximately 4.5- to 25-fold reduction) in subjects taking HS-10234 than those in the TDF group.

Conclusions: HS-10234 was well tolerated during a 4-week course. TDF and HS-10234 had comparable potency in inhibiting HBV replication. A daily dose of 10-25 mg of HS-10234 is recommended for CHB treatment. (Chinese Drug Trial Identifier: CTR20161077).

© 2020 John Wiley & Sons Ltd.

StephenW

隨機臨床試驗：HS-10234與替諾福韋治療慢性乙型肝炎的安全性，療效和藥代動力學
張洪1，胡越1，吳敏1，劉靜瑞1，朱小雪1，李小嬌1，洪紅1，李翠雲1，劉成嬌1，牛俊奇2，丁艷華1
隸屬關係
隸屬關係

    1個
    吉林大學第一醫院臨床一期研究中心，吉林
    2
    吉林大學第一醫院肝臟科，吉林

    PMID：33249630 DOI：10.1111 / apt.16196

抽象

背景：HS-10234是替諾福韋的新型前藥，其開發目的是提高抗病毒效力並降低全身毒性。

目的：評估HS-10234在慢性乙型肝炎（CHB）患者中的耐受性，藥代動力學和抗病毒療效。方法：將未接受治療的非肝硬化性CHB患者分為三組（n = 12 /組）並隨機分為兩組，每天接受一次10，25或40 mg的HS-10234或300毫克的替諾福韋富馬酸替諾福韋酯（TDF），持續28天。

結果：在36名受試者中，乙型肝炎e抗原陰性的患者佔33.3％，平均乙型肝炎病毒（HBV）DNA水平為6.32-7.42 log10 IU / mL。未觀察到腎毒性和嚴重不良事件。所有不良事件均為輕度或中度且非特異性。用10、25或40 mg HS-10234和300 mg TDF處理後，28天后血清HBV DNA的平均降低分別為-2.70，-2.89，-2.72和-3.04 log10 IU / mL。 HS-10234及其代謝產物TFV呈線性，與劑量成比例的藥代動力學。服用HS-10234的受試者的外周血單核細胞中活性TFV-DP的濃度較高（約增加2至11倍），血漿TFV較低（減少約4.5至25倍）。 TDF組。

結論：HS-10234在4週的療程中耐受良好。 TDF和HS-10234在抑制HBV複製方面具有可比的效力。建議每天服用10-25毫克的HS-10234進行CHB治療。 （中國藥品試驗編號：CTR20161077）。

分級為4 +©2020 John Wiley＆Sons Ltd.

齐欢畅

齐欢畅

10-毫克

liuzai

HS-10234 10毫克，副作用应该会比TAF还轻吧？

tim889

不直接和TAF比一点意义都没有。类似的药有CMX157, 最后也不了了之了。

乙肝人1949

889和你的观点一样，丅AF已出，机理一样或类似，意义不大。且TAF，明年已经可以仿制药出来了

乙肝人1949

价格己能可及了。还是来点创新的东东吧。没有搞头

tim889

不能只看10mg，要看摩尔质量转化成等量替诺夫韦才能比较

liuzai

回复 tim889 的帖子

怎么看？假设这个 每天10mg 是不是副作用会比TAF 还少？ 要是 每天10mg 的TAF  估计绝大部分人的副作用可以忽略不计