A Randomized, Double-blind, Placebo-controlled, First-in-human, 3 Part Study of Orally Administered AL-611 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Part 3) of Single Ascending Doses in Healthy Volunteers (Parts 1-2), and Multiple Ascending Doses in Subjects With Chronic Hepatitis C Virus Infection (Part 3)

This randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, pharmacokinetics (PK), and antiviral activity (Part 3 only) of orally administered AL-611 in healthy volunteers (HV; Parts 1-2) and subjects with CHC (Part 3).
Part 1: HV will receive 1 of 5 single ascending doses (SAD) of AL-611 Part 2: Eight HV from Cohort 3 in Part 1 are planned to receive a second single dose of AL-611 or placebo (as per their randomized assignment in Part 1) in a fed state after a washout period Part 3: Subjects with CHC infection will receive 1 of 3 planned multiple ascending doses (MAD)

开始日期2017-07-07

申办/合作机构

Alios BioPharma, Inc.

100 项与 AL-611 相关的临床结果

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100 项与 AL-611 相关的转化医学

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100 项与 AL-611 相关的专利（医药）

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项与 AL-611 相关的文献（医药）

2020-09-24·Journal of Medicinal Chemistry1区 · 医学

Synthesis and Anti-HCV Activity of Sugar-Modified Guanosine Analogues: Discovery of AL-611 as an HCV NS5B Polymerase Inhibitor for the Treatment of Chronic Hepatitis C

1区 · 医学

Article

作者: Williams, Caroline ; Gupta, Kusum ; Serebryany, Vladimir ; Smith, David B. ; Huang, Yongfei ; Beigelman, Leonid ; Fung, Amy ; Wang, Guangyi ; Dyatkina, Natalia ; Hu, Yujian ; Chen, Tongqian ; Jin, Zhinan ; Jekle, Andreas ; Tam, Yuen ; Deval, Jerome ; Huang, Wensheng ; Shaw, Kenneth ; Stoycheva, Antitsa ; Prhavc, Marija ; Wu, Xiangyang ; Rajwanshi, Vivek K.

Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8-16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2',3'- and 2',4'-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC₅₀ as low as 0.13 μM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC₅₀ values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5'-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.

100 项与 AL-611 相关的药物交易

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