Sang Hoon Ahn1, Won Kim2, Young Kul Jung3, Jin Mo Yang4, Jae Young Jang5, Yong Oh Kweon6, Yong Kyun Cho7, Yoon Jun Kim8, Gun Young Hong9, Dong Joon Kim10, Soon Ho Um3, Joo Hyun Sohn11, Jin Woo Lee12, Sung Jae Park13, Byung Seok Lee14, Ju Hyun Kim15, Hong Soo Kim16, Seung Kew Yoon17, Moon Young Kim18, Hyung Joon Yim3, Kwan Sik Lee1, Young Suk Lim19, Wan Sik Lee20, Neung Hwa Park21, So Young Jin5, Kyun-Hwan Kim22, Won Choi23, Kwang-Hyub Han24. 1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. 2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea. 3. Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea. 4. Department of Internal Medicine, Catholic University Medical College St Vincent's Hospital, Suwon, Korea. 5. Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea. 6. Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Korea. 7. Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 8. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. 9. Department of Internal Medicine, Kwangju Christian Hospital, Gwangju, Korea. 10. Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea. 11. Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. 12. Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea. 13. Department of Internal Medicine, Paik Hospital, Inje University, Pusan, Korea. 14. Department of Gastroenterology and Hepatology, Chungnam National University School of Medicine, Daejeon, Korea. 15. Department of Internal Medicine, Gacheon University College of Medicine, Incheon, Korea. 16. Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea. 17. Department of Internal Medicine, Catholic University of Korea, Seoul, Korea. 18. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. 19. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 20. Department of Internal Medicine, Chonnam University Medical School, Gwangju, Korea. 21. Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Korea. 22. Department of Pharmacology, School of Medicine, Konkuk University, Korea. 23. Ildong Pharmaceutical Co, Ltd, Seoul, Korea. 24. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: gihankhys@yuhs.ac.
Abstract
BACKGROUND & AIMS:Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. METHODS: We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks. RESULTS: After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. CONCLUSIONS:BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.
RCT Entities:
BACKGROUND & AIMS:Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea. METHODS: We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks. RESULTS: After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups. CONCLUSIONS:BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.
Authors: Daniel Castaneda; Adalberto Jose Gonzalez; Mohammad Alomari; Kanwarpreet Tandon; Xaralambos Bobby Zervos Journal: World J Gastroenterol Date: 2021-04-28 Impact factor: 5.742
Authors: Hyung Joon Yim; Won Kim; Sang Hoon Ahn; Jin Mo Yang; Jae Young Jang; Yong Oh Kweon; Yong Kyun Cho; Yoon Jun Kim; Gun Young Hong; Dong Joon Kim; Young Kul Jung; Soon Ho Um; Joo Hyun Sohn; Jin Woo Lee; Sung Jae Park; Byung Seok Lee; Ju Hyun Kim; Hong Soo Kim; Seung Kew Yoon; Moon Young Kim; Kwan Sik Lee; Young Suk Lim; Wan Sik Lee; Kwang-Hyub Han Journal: Am J Gastroenterol Date: 2020-08 Impact factor: 12.045