Tenofovir Alafenamide in HBV Related Decompensated Liver
Safety and Efficacy of Tenofovir Alafenamide for Chronic Hepatitis B Patients With Decompensated Liver Disease
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Tipo de estudo
Tipo de estudo
Inscrição (Antecipado)
Inscrição
Estágio
Estágio
- Fase 4
Contactos e Locais
Contato de estudo
Contato de estudo
- Nome: Ming-Lung Yu, Professor
- Número de telefone: 7475 886-7-3121101
- E-mail: fish6069@gmail.com
Locais de estudo
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Kaohsiung, Taiwan, 807
- Recrutamento
- Kaohsiung Medical University Hospital
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Contato:
- Ming-Lung Yu
- Número de telefone: 7475 +886-7-312-1101
- E-mail: fish6069@gmail.com
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Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Male or non-pregnant female, age ≥20 years
- Chronic HBV infection with positive hepatitis B surface antigen (HBsAg) for at least 6 months at screening.
- Hepatic decompensation, defined as Child-Turcotte-Pugh (CTP) score ≥7, or the presence of portal hypertension related complications including ascites, hepatic encephalopathy (<grade 2) at screening.
- HBV NUC treatment naïve or experienced (except prior TAF) for Arm A or currently under HBV NUC treatment (except TAF) with HBV DNA < 20 IU/mL within 6 months prior screening for Arm B.
- Patients with either liver cirrhosis or non-cirrhosis (defined by histology, non-invasive assessments, or imaging/clinical based diagnosis).
- Estimated creatinine clearance ≥30 ml/min (using the Cockcroft-Gault method) at screening. (Note: multiply estimated rate by 0.85 for women).
- Willing and able to provide informed consent
- Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments
Exclusion Criteria:
- Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study.
- Previous recipient of a solid organ (including liver), or bone marrow transplant.
- Severe or uncontrolled comorbidities determined by the Investigator.
- Currently ≥grade 2 hepatic encephalopathy, currently or history (within 60 days) of variceal bleeding, hepatorenal syndrome, refractory ascites or spontaneous bacterial peritonitis; cytopenia of absolute neutrophil count < 750/mm3, or hemoglobin < 8 g/dL, or platelet <30000/mm3; or MELD score ≥30 at screening.
- Malignancy history including hepatocellular carcinoma, except basal cell skin cancer without recurrence for more than 5 years.
- Acute exacerbation of HBV, defined as an elevation of alanine aminotransferase (ALT) activity to more than 10 times the upper limit of normal and more than twice the baseline value.
- On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 16). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening.
- Males and females of reproductive potential who are unwilling to use "effective" protocol-specified method(s) of contraception during the study.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
|---|---|
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Experimental: Arm A - initial TAF treatment group
cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and HBV NUC treatment naïve or experienced (except prior TAF) will receive initial treatment (Arm A) with TAF 25 mg/day.
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Approximately 100 adults, cirrhotic or non-cirrhotic (capped at 50), CHB patients with hepatic decompensation, will receive initial treatment (Arm A) with or switch (Arm B) to TAF 25 mg/day for 144 weeks.
For Initiation Arm (Arm A), CHB patients with hepatic decompensation, who are currently not under HBV antiviral treatment will be enrolled.
For Switch Arm (Arm B), CHB patients who are currently with hepatic decompensation and virally suppressed under HBV NUC treatment (HBV DNA < 20 IU/mL) will be enrolled.
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Experimental: Arm B - switch to TAF treatment group
cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and currently under HBV NUC treatment (except TAF) with HBV DNA < 20 IU/mL within 6 months prior screening will switch (Arm B) to TAF 25 mg/day
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Approximately 100 adults, cirrhotic or non-cirrhotic (capped at 50), CHB patients with hepatic decompensation, will receive initial treatment (Arm A) with or switch (Arm B) to TAF 25 mg/day for 144 weeks.
For Initiation Arm (Arm A), CHB patients with hepatic decompensation, who are currently not under HBV antiviral treatment will be enrolled.
For Switch Arm (Arm B), CHB patients who are currently with hepatic decompensation and virally suppressed under HBV NUC treatment (HBV DNA < 20 IU/mL) will be enrolled.
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O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Complete virological suppression
Prazo: week 48
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Proportion of patients treated with TAF who achieve complete virological suppression (HBV DNA < 20 IU/ml) at week 48 of TAF therapy in per-protocol (PP) population.
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week 48
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Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Rate of adverse events
Prazo: week 48
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Rate of adverse events including serious adverse events and discontinuation at Week 48
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week 48
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Rate of recovery from hepatic decompensation
Prazo: week 48, 96, and 144
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Rate of recovery from hepatic decompensation (improvement of CTP score ≥1) at week 48, 96, and 144 of TAF therapy in FAS, modified FAS (mFAS) and PP populations.
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week 48, 96, and 144
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Liver transplant-free survival
Prazo: week 48, 96, and 144
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Liver transplant-free survival at week 48, 96, and 144 of TAF therapy in FAS, mFAS and PP populations.
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week 48, 96, and 144
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Rate of virological response
Prazo: week 96, and 144
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Rate of virological response (HBV DNA < 20 IU/ml) at week 96, and 144 of TAF therapy
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week 96, and 144
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Rate of ALT normalization
Prazo: week 48, 96, and 144
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Rate of ALT normalization by local (<40 U/L), and AASLD (male ≤35, female ≤25 U/L) criteria at week 48, 96, and 144 of TAF therapy in FAS, mFAS and PP populations.
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week 48, 96, and 144
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Rate of HBeAg loss/seroconversion, HBsAg loss/seroconversion
Prazo: week 48, 96, and 144
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Rate of HBeAg loss/seroconversion in baseline HBeAg-seropositive patients, HBsAg loss/seroconversion, and change in HBsAg titer at week 48, 96, and 144 of TAF therapy.
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week 48, 96, and 144
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Changes of serum creatinine
Prazo: week 48, 96, and 144
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Changes of serum creatinine from baseline to week 48, 96, and 144 of TAF in mFAS and PP populations.
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week 48, 96, and 144
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Changes of calculated creatinine clearance
Prazo: week 48, 96, and 144
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Changes of calculated creatinine clearance (Cockcroft-Gault) from baseline to week 48, 96, and 144 of TAF in mFAS and PP populations.
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week 48, 96, and 144
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Changes in bone mineral density
Prazo: week 144
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Changes in bone mineral density from baseline to week 144 of TAF in mFAS and PP populations.
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week 144
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Changes in value of transient elastography
Prazo: week 144
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Changes in value of transient elastography (Fibroscan, kPa) from baseline to week 144 in mFAS and PP populations.
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week 144
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Changes in body mass index
Prazo: week 48, 96, and 144
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Changes in body mass index (BMI) from baseline to week 48, 96, and 144 of TAF in mFAS and PP populations.
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week 48, 96, and 144
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Changes in blood lipid profile
Prazo: week 48, 96, and 144
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Changes in fasting blood lipid profiles from baseline to week 48, 96, and 144 of TAF in mFAS and PP populations.
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week 48, 96, and 144
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Changes in blood glucose
Prazo: week 48, 96, and 144
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Changes in fasting blood glucose from baseline to week 48, 96, and 144 of TAF in mFAS and PP populations.
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week 48, 96, and 144
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Ming-Lung Yu, Professor, Hepatobiliary Division, Kaohsiung Medical University Hospital
Publicações e links úteis
Publicações Gerais
- Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
- European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
- Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar;11(2):97-107. doi: 10.1046/j.1365-2893.2003.00487.x.
- Liaw YF, Chu CM. Hepatitis B virus infection. Lancet. 2009 Feb 14;373(9663):582-92. doi: 10.1016/S0140-6736(09)60207-5.
- Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
- Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, Mehta R, Gane E, Flaherty JF, Massetto B, Gaggar A, Kitrinos KM, Lin L, Subramanian GM, McHutchison JG, Lim YS, Acharya SK, Agarwal K; GS-US-320-0110 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):185-195. doi: 10.1016/S2468-1253(16)30024-3. Epub 2016 Sep 22. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
- Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Clin Liver Dis (Hoboken). 2018 Aug 22;12(1):33-34. doi: 10.1002/cld.728. eCollection 2018 Jul. No abstract available.
- Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol. 2000 Aug;33(2):301-7. doi: 10.1016/s0168-8278(00)80371-2.
- Fontana RJ, Hann HW, Perrillo RP, Vierling JM, Wright T, Rakela J, Anschuetz G, Davis R, Gardner SD, Brown NA. Determinants of early mortality in patients with decompensated chronic hepatitis B treated with antiviral therapy. Gastroenterology. 2002 Sep;123(3):719-27. doi: 10.1053/gast.2002.35352.
- Schiff E, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, Colombo M, Tillmann H, Samuel D, Zeuzem S, Villeneuve JP, Arterburn S, Borroto-Esoda K, Brosgart C, Chuck S; Adefovir Dipivoxil Study 45 Intrnational Investigators Group. Adefovir dipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results. Liver Transpl. 2007 Mar;13(3):349-60. doi: 10.1002/lt.20981.
- Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, Lee YS, Suh DJ. Efficacy of entecavir in treatment-naive patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol. 2010 Feb;52(2):176-82. doi: 10.1016/j.jhep.2009.11.007. Epub 2009 Dec 16.
- Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, Suet-Hing Wong F, Chang TT, Horban A, Wang C, Kwan P, Buti M, Prieto M, Berg T, Kitrinos K, Peschell K, Mondou E, Frederick D, Rousseau F, Schiff ER. Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology. 2011 Jan;53(1):62-72. doi: 10.1002/hep.23952. Epub 2010 Oct 27.
- Dai CY, Chuang WL, Hou NJ, Lee LP, Hsieh MY, Lin ZY, Chen SC, Huang JF, Hsieh MY, Wang LY, Tsai JF, Wen-Yu, Yu ML. Early mortality in Taiwanese lamivudine-treated patients with chronic hepatitis B-related decompensation: evaluation of the model for end-stage liver disease and index scoring systems as prognostic predictors. Clin Ther. 2006 Dec;28(12):2081-92. doi: 10.1016/j.clinthera.2006.12.016.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Início do estudo
Conclusão Primária (Antecipado)
Conclusão Primária
Conclusão do estudo (Antecipado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
Outros números de identificação do estudo
- TAF-Deliver
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