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      • KCI등재

        Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients

        Jinlin Hou,Edward Gane,Rozalina Balabanska,Wenhong Zhang,Jiming Zhang,Tien Huey Lim,Qing Xie,Chau-Ting Yeh,Sheng-Shun Yang,Xieer Liang,Piyawat Komolmit,Apinya Leerapun,Zenghui Xue,Ethan Chen,Yuchen Zh 대한간학회 2024 Clinical and Molecular Hepatology(대한간학회지) Vol.30 No.2

        Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

      • Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Non-Cirrhotic Asian Patients with Genotype 1b HCV Infection: ONYX-I SVR24 Results

        ( Lai Wei ),( Jinlin Hou ),( Yan Luo ),( Jeong Heo ),( Chi-jen Chu ),( Zhongping Duan ),( Mong Cho ),( Jun Cheng ),( Jun Li ),( Jidong Jia ),( Wenjing Lu ),( Linda M Fredrick ),( Tami Pilot-matias ),( 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: HCV genotype 1b is the most common genotype in Asian patients. ONYX-I is a phase 3, randomised, double-blind, placebo-controlled study of the 3-DAA regimen of OBV/PTV/r and DSV in treatment- naive and treatment-experienced non-cirrhotic patients with HCV GT1b infection in China, South Korea and Taiwan. Methods: In this study, the safety/efficacy of OBV/PTV/r + DSV administered for 12 weeks were evaluated in non-cirrhotic Asian patients. Patients in Arm A received active study drug during a 12-week double-blind (DB) period, while patients in Arm B received placebo during the same period followed by an open-label (OL) period in which they received 12 weeks of active study drug. Efficacy was assessed by SVR12 and SVR24. Efficacy and safety were assessed in all patients who received at least one dose of active study drugs. Results: 650 HCV GT1b patients (54% female, 100% Asian, 44% treatment-experienced) were enrolled from China (n=410) South Korea (n=120) and Taiwan (n=120), and randomised 1:1 to Arms A and B. In Arm A, SVR12 and SVR24 rates were 99.5% (183/184) in treatment-naive patients and 100% (141/141) in treatment- experienced patients. Most treatment-emergent adverse events (TEAEs) in patients receiving the active drug were mild in severity. The most common (≥5%) TEAEs in Arm A were upper respiratory tract infection (10.5%), headache (6.2%) and dizziness (5.2%). Seven patients had serious AEs during active treatment (Arm A) and one patient in Arm A discontinued treatment. Conclusions: In non-cirrhotic Asian adults with HCV GT1b-infection, treated with OBV/PTV/r + DSV for 12 weeks, SVR24 rates equalled previously reported SVR12 rates from this study (99.5% of treatment- naive and 100% of treatment-experienced patients), and are consistent with other clinical trials with this drug combination. The treatment was generally well tolerated with mostly mild TEAEs reported.

      • KCI등재

        Metal-Free Photocatalysts C3N3S3 and its Polymers: Solubility in Water and Application in Benzylic Alcohols Oxidation Under Visible Light

        Liming Chen,Lulu Zhao,Jie Xu,Jinlin Long,Linxi Hou 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2017 NANO Vol.12 No.8

        Metal-free photocatalysts trithiocyanuric acid (C3N3S3) and its polymers were one-step synthesized and used for selective aerobic oxidation of benzyl alcohol under visible light. The S–S bridged C3N3S3 polymers showed higher oxidation activity with increasing polymerization time and reached a maximum at 40 h. As a major factor, catalysts' solubility in water at different temperatures (from 298.15K to 368.15 K) was measured at atmospheric pressure. The obtained data were correlated by polynomial empirical equation and modified Apelblat equation, respectively. Experimental results proved that the solubility of C3N3S3 and its polymers increased with increasing temperature. The solubility of C3N3S3 polymers with lower polymerization degree (DP) were better than that of parent C3N3S3 owing to the hydrophilicity caused by a low symmetry and disorder structure, whereas the higher DP could lead to the decrease of polymer solubility and further affect the photocatalytic activity. Thermodynamic properties of the solution system including the enthalpy (△H0S) and heat capacity (c0p) were calculated by the modified Apelblat equation.

      • Efficacy/Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin in Asian Patients with Genotype 1b HCV-Infected, Compensated Cirrhosis: ONYX-II SVR 24 Results

        ( Lai Wei ),( Gui-qiang Wang ),( Yan Luo ),( Chi-jen Chu ),( Seung Woon Paik ),( Jinlin Hou ),( Jun Cheng ),( Qing Xie ),( Zhongping Duan ),( Jia-horng Kao ),( Linda Fredrick ),( Bo Fu ),( Niloufar Mo 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: ONYX-II is a phase 3, open-label study of 3-DAA regimen of OBV/PTV/r and DSV with RBV in treatment-naive and experienced patients with genotype 1b HCV infection and compensated cirrhosis in China, South Korea and Taiwan. SVR12 rate was 100% and the favourable safety profile was shown. The present analysis reports efficacy( SVR24) and safety results. Methods: Patients with chronic GT1b HCV infection and compensated cirrhosis received OBV/PTV/r + DSV + RBV for 12 weeks and will be followed for 48 weeks post-treatment. Efficacy was assessed by SVR12 and SVR24. Safety was assessed as the percentage of patients wi th treatment-emergent adverse events (TEAEs) and laboratory evaluation. Results: Total of 104 patients with chronic GT1b HCV infection (62% female, 100% Asian, 58% treatment-experienced) were enrolled from China (n=63), South Korea (n=21) and Taiwan (n=20). All patients received at least one dose of study drugs. The SVR24 rate was 100% (concordant with SVR12), with no patient relapsing between post-treatment week 12 and 24. Most TEAEs were mild in severity. The most common TEAEs (≥10%) were increased blood bilirubin levels (25%), pruritus (15%), anaemia (14%), asthenia (12%), bilirubin conjugated increased (12%), blood bilirubin unconjugated increased (12%), dizziness (11%) and fatigue (11%). Four patients had serious AEs and all were assessed as not being related to the 3-DAA regimen (one was assessed as being possibly related to RBV). One patient discontinued treatment due to TEAEs (elevations in alanine aminotransferase [ALT], aspartate aminotransferase [AST] and blood bilirubin) after 3 weeks of dosing but achieved SVR12 and SVR24. Laboratory abnormalities ≥ grade 3 were infrequent (ALT: 3%; AST 2%; total bilirubin: 7%). No grade 3 haemoglobin decrease was reported. Conclusions: SVR24 and SVR12 rates were concordant (100%) in HCV GT1b-infected Asian patients with compensated cirrhosis. The regimen was generally well tolerated with mostly mild TEAEs reported.

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