Dicerna Pharma（DRNA）报告在DCR-HBVS治疗慢性乙型肝炎病毒的第一

StephenW

Dicerna Pharma (DRNA) Reports First Patient Dosing in Phase 1 Clinical Trial of DCR-HBVS for the Treatment of Chronic Hepatitis B Virus

Dicerna Pharmaceuticals, Inc. (NASDAQ: DRNA) today announced the dosing of the first patient in its Phase 1 clinical trial of DCR-HBVS, the Company’s investigational GalXCTM-based therapy for the treatment of chronic hepatitis B virus (HBV) infection in adults. The Company anticipates human proof-of-concept data from the Phase 1 trial, which is known as DCR-HBVS-101, in the fourth quarter of 2019. In January 2019, Dicerna announced the dosing of the first human volunteer in this Phase 1 study.

“Dosing of the first patient in the DCR-HBVS-101 trial signals a major step toward our ultimate goal of developing a viable therapeutic option for patients with chronic hepatitis B virus, a serious liver infection that can result in advanced liver disease or liver cancer if not treated effectively,” said Ralf Rosskamp, M.D., chief medical officer of Dicerna. “Based upon our encouraging preclinical data with DCR-HBVS and our initial experience with the healthy volunteers who are enrolled in this trial, we are optimistic about the clinical potential of RNA interference as an innovative approach to effectively treat chronic hepatitis B virus infection.”

The DCR-HBVS-101 clinical trial is a Phase 1, randomized, placebo-controlled study designed to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers (HVs) and in patients with non-cirrhotic chronic HBV infection. Secondary objectives are to characterize the pharmacokinetic profile of DCR-HBVS and to evaluate preliminary pharmacodynamics and antiviral efficacy on plasma levels of hepatitis B surface antigen (HBsAg) and HBV DNA in blood.

DCR-HBVS is comprised of a single GalXC molecule that targets HBV messenger RNAs within the HBsAg gene sequence region. Preclinical studies with a standard mouse model of HBV infection showed DCR-HBVS led to greater than 99% reduction in circulating HBsAg, suggesting a level of HBsAg suppression (both in magnitude and duration of suppression) that may be greater than that achieved from targeting within the X gene sequence region.

“Given the encouraging inhibitory activity of DCR-HBVS in animal studies, its favorable preclinical safety profile, and the lack of major safety signals among healthy volunteers dosed thus far in the DCR-HBVS-101 trial, we eagerly anticipate the results from patients with chronic hepatitis B who are treated with DCR-HBVS,” said Man-Fung Yuen, D.Sc., M.D., Ph.D., Professor of Medicine and Chair of Gastroenterology and Hepatology at the University of Hong Kong. “Unlike other therapeutic approaches to treating chronic HBV infection, DCR-HBVS leverages the power of RNA interference to silence multiple viral genes in addition to the S antigen, potentially reducing HBsAg to very low levels, which could allow the patient’s own immune system to generate an effective immune response. With its long-acting mechanism, DCR-HBVS may help patients with chronic HBV infection achieve a functional cure.”

DCR-HBVS-101 Trial Design

The DCR-HBVS-101 clinical trial is divided into three phases or groups:

    In Group A, 30 HVs are to receive a single ascending-dose of DCR-HBVS (0.1, 1.5, 3, 6, or 12 mg/kg) or placebo, with a four-week follow-up period.
    Group B is a single-dose arm in which eight participants with HBV who are naïve to nucleoside analog therapy will receive a 3 mg/kg dose of DCR-HBVS or placebo; these participants will be followed for at least 12 weeks. The Company expects to initiate Group B dosing in the third quarter of 2019, in parallel with Group C at the 3 mg/kg dose level.
    Group C is a multiple ascending dose arm in which DCR-HBVS (1.5, 3, or 6 mg/kg) or placebo will be administered to 18 participants with HBV who are already being treated with nucleoside analogs, with a treatment and follow-up period of 16 weeks or more. The first participant dosed was from this group, at a dose of 1.5 mg/kg.

Study participants in Groups B and C, in whom HBsAg will have dropped by more than 1 log10 IU/mL below baseline at their last scheduled study visit, will continue to be followed until their HBsAg level is less than 1 log10 IU/mL below the baseline value.

For more information about the DCR-HBVS-101 clinical trial, please visit www.clinicaltrials.gov and use the identifier NCT03772249.

StephenW

Dicerna Pharma（DRNA）报告在DCR-HBVS治疗慢性乙型肝炎病毒的第一阶段临床试验中首例患者给药

Dicerna Pharmaceuticals，Inc。（纳斯达克股票代码：DRNA）今天宣布在第一期DCR-HBVS临床试验中给予第一名患者，该研究是基于GalXCTM的研究，用于治疗成人慢性乙型肝炎病毒（HBV）感染。公司预计2019年第四季度的第一阶段试验（称为DCR-HBVS-101）的人体概念验证数据。在2019年1月，Dicerna宣布第一阶段第一个人类志愿者的剂量计划研究。

“DCR-HBVS-101试验中第一位患者的给药标志着我们为慢性乙型肝炎病毒患者开发一种可行的治疗选择的最终目标迈出了重要一步，这种病毒是一种严重的肝脏感染，可导致晚期肝病或肝癌如果没有得到有效治疗，“Dicerna首席医疗官Ralf Rosskamp博士说。 “基于我们令人鼓舞的DCR-HBVS临床前数据以及我们参加本试验的健康志愿者的初步经验，我们对RNA干扰作为一种有效治疗慢性乙型肝炎病毒感染的创新方法的临床潜力持乐观态度。”

DCR-HBVS-101临床试验是一项随机，安慰剂对照研究，旨在评估DCR-HBVS在健康志愿者（HV）和非肝硬化慢性HBV感染患者中的安全性和耐受性。次要目标是表征DCR-HBVS的药代动力学特征，并评估血液中乙型肝炎表面抗原（HBsAg）和HBV DNA血浆水平的初步药效学和抗病毒效力。

DCR-HBVS由单个GalXC分子组成，其靶向HBsAg基因序列区域内的HBV信使RNA。使用HBV感染的标准小鼠模型进行的临床前研究显示，DCR-HBVS导致HBsAg循环减少超过99％，表明HBsAg抑制水平（抑制的幅度和持续时间）可能大于内靶定的水平。 X基因序列区。

“鉴于DCR-HBVS在动物研究中具有令人鼓舞的抑制活性，其良好的临床前安全性以及迄今为止在DCR-HBVS-101试验中健康志愿者中缺乏主要安全性信号，我们热切期待患者的结果。接受DCR-HBVS治疗的慢性乙型肝炎，“医学博士，医学博士，香港大学胃肠病学和肝病学系主任Man-Fung Yuen博士说。 “与治疗慢性HBV感染的其他治疗方法不同，DCR-HBVS利用RNA干扰的能力来沉默除S抗原之外的多种病毒基因，可能将HBsAg降低到非常低的水平，这可能使患者自身的免疫系统产生有效的免疫反应。凭借其长效机制，DCR-HBVS可以帮助慢性HBV感染患者实现功能性治愈。“

DCR-HBVS-101试验设计

DCR-HBVS-101临床试验分为三个阶段或组：

    在A组中，30个HV将接受单次递增剂量的DCR-HBVS（0.1,1.5,3,6或12mg / kg）或安慰剂，并且具有四周的随访期。
    B组是单剂量组，其中8名HBV参与者对核苷类似物治疗是天真的，将接受3 mg / kg剂量的DCR-HBVS或安慰剂;这些参与者将被跟踪至少12周。公司预计在2019年第三季度开始B组给药，与C组同时给药3 mg / kg剂量水平。
    C组是一个多次递增剂量组，其中DCR-HBVS（1.5,3或6 mg / kg）或安慰剂将给予已经接受核苷类似物治疗的18名HBV参与者，并进行治疗和随访期限为16周或以上。第一个参与者来自该组，剂量为1.5mg / kg。

B组和C组的研究参与者将继续接受HBsAg在最后一次预定的研究访视时下降超过1 log10 IU / mL的研究参与者，直到他们的HBsAg水平低于1 log10 IU / mL。基线值。

有关DCR-HBVS-101临床试验的更多信息，请访问www.clinicaltrials.gov并使用标识符NCT03772249

灵魂不屈

感谢分享。这个药是新研发的吗？以前没有看到过相关信息。

StephenW

回复 灵魂不屈 的帖子

不是新的, 另一个RNAi: DCR-HBVS是单个GalXC分子，其靶向HBsAg基因序列区域内的HBV mRNA。尚不清楚其他病毒蛋白会, 除了s-抗原, 试图沉默.