Hepatitis B, ChronicPhase 4NCT04201808
Efficacy and Safety of TAF in Patients With Suboptimal Response to Other Nucleos(t)Ides
A Phase 4 study testing Tenofovir Alafenamide 25 MG in people with Hepatitis B, Chronic, run by New Discovery LLC at 10 sites in China.
Trial summary
Both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are potent antiviral agents for hepatitis B virus (HBV) and recommended by the American Association for the Study of Liver Disease (AASLD) as well as the European Association for the Study of Liver (EASL) guidelines for the treatment of… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Tenofovir Alafenamide 25 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 10 sitesChina
- Study dates
- 1 May 2021to 30 Sep 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be 18-80 years of age.
- Patients must have documented compensated and stable chronic hepatitis B defined by all of the following:
- HBsAg persistently positive > 6 months.
- Clinical history, physical findings, and test results are compatible with compensated chronic hepatitis B
- Patients must have received nucleos(t)ide therapy consisting of LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks with medication adherence.
- Although having undergone therapy, patients have had failure to achieve the levels of HBV-DNA below 300 IU/mL.
- Patient is willing and able to comply with the study drug regimen and all other study requirements.
- Patient must understand the risk, and be willing and able to provide written informed consent to participate in the study.
Who cannot join
- Pregnant women, and women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
- Males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception.
- Unwilling and/or unable to provide written informed consent
- Patients with CHB but are also co-infected with HIV or other viral hepatitis
- Patients whose serum levels of HBV DNA are too low (i.e. about 300 IU/mL) to be analyzed for the genotypic mutation(s) at the onset of this trial, i.e. baseline
- At the screening visit, nucleos(t)ide resistant mutants have been detected in the strain of HBV of the patient
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- The patient is under a clinical research protocol of phase I-III development; unable to consent or unlikely to complete one year follow up after the enrollment; and other medical condition may affect the ability to participate the study.
- Decompensated liver disease defined as direct (conjugated) bilirubin ≥ 1.2 Upper Limit of Normal (ULN); Prothrombin Time (PT) ≥ 1.2 ULN, platelets ≤ 150,000/mm3, or serum albumin ≤ 3.5 g/dL
- Prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy) or variceal hemorrhage
- Serum α-fetoprotein ≥ 50 ng/mL
- Evidence of hepatocellular carcinoma (HCC)
- History of significant renal disease (e.g., nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
- History of significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures)
- Significant cardiovascular, pulmonary or neurological disease
- Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
- History of solid organ or bone marrow transplantation
- Ongoing therapy with any of the following: Nephrotoxic agents
- Parenteral aminoglycoside antibiotics (e.g., gentamicin, tobramycin, amikacin)
- Cidofovir
- Cisplatin
- Foscarnet
- IV amphotericin B
- IV pentamidine
- Oral or IV ganciclovir
- Cyclosporine
- Tacrolimus
- IV vancomycin
- Chronic daily non-steroidal anti-inflammatory drug therapy
- Competitors of renal excretion (e.g., probenecid) Systemic chemotherapeutic agents
- Systemic corticosteroids
- Interleukin-2 (IL-2) and other immunomodulating agents
- Investigational agents (except with the expressed approval of the lead investigators)
- Note: administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period.
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigators, would make the subject unsuitable for the study or unable to comply with dosing requirements
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
China10 sites, 10 recruiting
- Recruiting
Beijing Ditan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100015
Qi Wang, MD, (+86) 15611265361, Wangqidl04@126.com
Wen Xie, MD, (+86) 13651113763, Xiewen6218@163.com
- Recruiting
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233000
Wei Li, MD, (+86) 13955292316, liwei79722.student@sina.com
Shousong' Zhao, MD, (+86) 13955215571, 1260345655@qq.com
- Recruiting
Southwest Hospital
Chongqing, Chongqing Municipality, 400038
Yuming Wang, MD, (+86) 023-65334998, wym417@163.com
Hongfei Huang, MD, (+86) 13983068253, huanghongfei1987@126.com
- Recruiting
Liver Research Center, The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Su Lin, MD, (+86) 13809505042, sumer5129@fjmu.edu.cn
Yueyong Zhu, MD, (+86) 13950233535, zhuyueyong@fjmu.edu.cn
- Recruiting
Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510630
Bixin Xu, MD, (+86) 13622286803, 718366615@qq.com
Zhiliang Gao, MD, (+86) 18922102588, gaozl@21cn.com
- Recruiting
The Third Hospital of Hebei Medical University
Hebei, Shijiazhuang, 050035
Ru Ji, MD, (+86) 15511643992, jiru0803@163.com
Cai-Yan Zhao, MD, (+86) 18533112898, zhaocy2015@163.com
- Recruiting
Huashan Hospital Fudan University
Jing’an, Shanghai Municipality, 200040
Chen Chen, MD, (+86) 13916484390, atheran@163.com
Wenhong Zhang, MD, (+86) 13801844344, zhangwenhong@fudan.edu.cn
- Recruiting
Shengjing Hospital of China Medical University
Shengyang, Liaoning, 110004
Qiuju Sheng, MD, (+86) 18940254812, shengqj@sj-hospital.org
Xiaoguang Dou, MD, (+86) 18940251121, guang40@163.com
- Recruiting
Wuhan Union Hospital, Tongji Medical College (TJMC), Huazhong University of Science and Technology (HUST)
Wuhan, Hubei, 430022
Wei Li, MD, (+86) 13657254656, lsnlw@sina.com
Dongliang Yang, MD, (+86) 13971063026, dlyang@hust.edu.cn
- Recruiting
Department of Infectious Diseases, Xi'an Jiaotong University Second Affiliated Hospital
Xi'an, Shaanxi, 710004
Le Ma, MD, (+86) 15029554007, happymale@163.com
Shuang-suo Dang, MD, (+86) 13992896471, dang212@126.com
About this study
Official title: Efficacy and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients With Suboptimal Response Following Nucleos(t)Ide Therapy
Both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are potent antiviral agents for hepatitis B virus (HBV) and recommended by the American Association for the Study of Liver Disease (AASLD) as well as the European Association for the Study of Liver (EASL) guidelines for the treatment of nucleos(t)ide therapy induced HBV resistance. However, it is not clear if chronic hepatitis B (CHB) patients with nucleos(t)ide treatment experience without genotypic mutations would be benefit from TAF therapy. Previous studies have observed that suboptimal response (SOR) following antiviral therapy with nucleos(t)ide treatment is associated with an increased risk of subsequent treatment failure and viral resistance. It remains unclear whether switching to TAF is a reasonable approach in patients with SOR to second-line antivirals Lamivudine (LAM)/ Telbivudine (LdT)/ Adefovir Dipivoxil (ADV) and its combinations with other second-line antivirals for 24 weeks, or SOR to the first-line antiviral Entecavir (ETV) or any antiviral combinations containing ETV for 48 weeks. This study is aimed to determine how the aforementioned patients with SOR to nucleos(t)ide treatment respond to TAF monotherapy. The investigator's study will provide evidence base for therapy selection in SOR patients, especially in China where the majority of patients with CHB are treated with nucleos(t)ide therapy.
Read the detailed description
This is a prospective, single-arm, multicenter cohort study evaluating the efficacy, safety, and tolerability of TAF monotherapy in in Asian CHB adults with SOR to the nucleos(t)ide therapy by assessing the HBV DNA suppression in 48 weeks. Approximately one hundred adults who received the aforementioned nucleos(t)ide therapy will be prospectively enrolled during the period from December 2019 to June 2021. Subjects will be enrolled by medical clinic in about 10 university centers in different regions in China. Approximately 10-15 consecutive eligible patients will be enrolled from each participating sites. This study will be conducted in accordance with the guidelines of Good Clinical Practices (GCPs) including Institutional Review Board (IRB) approval and consent will be applied. Patient identification (ID) will be de-identified for submitting to the central database for analyses from all study sites. Free TAF treatment will be provided to all enrolled patients for 48 weeks. Patients will be under the local standard of care upon the completion of the current study.
Patients aged 18-80 with CHB infection who had received nucleos(t)ide therapy over 24 weeks of LAM/LdT/ADV or 48 weeks of ETV with medication adherence, but failure to achieve the levels of HBV-DNA below 300 IU/mL will be eligible. Subjects will be excluded if they meet the following criteria: co-infected with HIV or other viral hepatitis; the serum levels of HBV DNA are too low (i.e. about 300 IU/mL) to be analyzed for the genotypic mutation(s); nucleos(t)ide resistant mutants have been detected at screening visit, patient is under a clinical research protocol of phase I-III development; unable to consent or unlikely to complete one year follow up after the enrollment; and other medical condition may affect the ability to participate the study.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Tenofovir Alafenamide 25 MG
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir Alafenamide 25 MGDrug
Also called Vemlidy
All patients will receive Tenofovir Alafenamide, 25mg PO, to treat chronic hepatitis B and their previous suboptimal response over the study duration of 48 weeks. Patients will be followed every 12 weeks for medication adherence, medication refill, and follow up as per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Intervention Group | Experimental | All approximately 100 patients experienced previous suboptimal response to other direct acting antivirals. Patients must have received nucleos(t)ide therapy consisting of LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks with medication adherence. All patients in this study are in the same arm. Receives: Drug: Tenofovir Alafenamide 25 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
this study seeks to evaluate the efficacy of TAF in Asian CHB adults with a proven SOR to previous nucleo(t)side therapy by assessing the percentage of patients who achieve HBV DNA viral suppression over a time span of 48 weeks.
In this study, HBV DNA viral suppression is defined as a HBV DNA level <20 IU/mL, and previous nucleo(t)side therapy is defined as treatments including LAM, LdT, ADV, and ETV before switching to TAF. The parameters for SOR will be set as patients who exhibit a 1 log10 IU/mL decrease in HBV DNA with medication adherence, but still present with an HBV DNA level of >300 IU/mL and has no detectable genotype mutation(s) when treated with the second-line antivirals LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or treated with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks.
Measured: 48 weeks
Secondary outcomes (7)
Incidence of Treatment-Emergent Adverse Events in Patients as stratified by the CTCAE v 5.0
Assess the percentage of Asian CHB adults with SOR to nucleos(t)ide therapy who have adverse events during the study, graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
Measured: At 12, 24, 36, and 48 weeks
Percentage of Patients Who Discontinue the Therapy Due to Issues with Tolerability
To evaluate the frequency of treatment discontinuation in patients who can not tolerate TAF therapy
Measured: At 12, 24, 36, and 48 weeks
Percentage of patients with Alanine transferase (ALT) levels within the normal limit
To calculate the percentage of patients at the end of 48 weeks whose ALT (U/L) levels stay within the normal limit in response to TAF therapy in Asian adults with CHB infection who are SOR to nucleos(t)ide therapy.
Measured: 48 weeks
Percentage of patients with Aspartamine transferase (AST) levels within the normal limit
To calculate the percentage of patients at the end of 48 weeks whose AST (U/L) levels stay within the normal limit in response to TAF therapy in Asian adults with CHB infection who are SOR to nucleos(t)ide therapy.
Measured: 48 weeks
Percentage of patients who experience loss/seroconversion of HBsAg and/or HBeAg during the study.
Assess the percentage of patients who loss/seroconversion of HBsAg or/and HBeAg during the study. Loss is defined by a test showing a negative HBsAg/HBeAg result at the end of the trial, given a positive respective test result at baseline. A seroconversion is defined as a test showing a negative HBsAg and a positive HBsAb result, or a negative HBeAg and a positive HBeAb result at the end of the trial, given a positive HBsAg/HBeAg test result at baseline.
Measured: 48 weeks
Percentage of patients with detectable drug resistance mutations
To evaluate the incidence of drug resistance and drug resistance mutations in 48 weeks of TAF treatment if patients have HBV DNA levels >300 IU/mL. Drug resistance by population sequencing and genotyping will be done for these patients.
Measured: 48 weeks
Percentage of patients who have skipped TAF treatment during the study
Assess the medication compliance on patients and compare the two sub-groups of patients who will be stratified by the levels of HBV DNA using the cut of of 20 IU/mL at 48 weeks.
Measured: 48 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2019
- Study start1 May 2021 (estimated)
- Primary completion30 Sep 2023 (estimated)
- Study completion30 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is single-arm, multicenter cohort study evaluating the efficacy, safety, and tolerability of TAF monotherapy in Asian CHB adults with SOR to the nucleos(t)ide therapy by assessing the HBV DNA suppression over a duration of 48 weeks.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New Discovery LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Beijing Ditan Hospital
- Responsible party
- Sponsor
- Investigators
- Calvin Q Pan, MD, Principal investigator, NYU Langone HealthWen Xie, MD, Study director, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04201808
- Sponsor's protocol ID
- IN-CN-320-5556
- Status last verified
- Dec 2019
- First submitted
- 6 Dec 2019
- Last updated
- 17 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.
PubMed 29756595Buti 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.
PubMed 28404092European 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.
PubMed 28427875Lu L, Yip B, Trinh H, Pan CQ, Han SH, Wong CC, Li J, Chan S, Krishnan G, Wong CC, Nguyen MH. Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir. J Viral Hepat. 2015 Aug;22(8):675-81. doi: 10.1111/jvh.12368. Epub 2014 Nov 24.
PubMed 25417914Pan CQ, Chan S, Trinh H, Yao A, Bae H, Lou L. Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B. World J Gastroenterol. 2015 May 14;21(18):5524-31. doi: 10.3748/wjg.v21.i18.5524.
PubMed 25987775Pan CQ, Hu KQ, Yu AS, Chen W, Bunchorntavakul C, Reddy KR. Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir. J Viral Hepat. 2012 Mar;19(3):213-9. doi: 10.1111/j.1365-2893.2011.01533.x. Epub 2011 Oct 17.
PubMed 22329376Terrault 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. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
PubMed 29405329Tong MJ, Pan CQ, Han SB, Lu DS, Raman S, Hu KQ, Lim JK, Hann HW, Min AD. An expert consensus for the management of chronic hepatitis B in Asian Americans. Aliment Pharmacol Ther. 2018 Apr;47(8):1181-1200. doi: 10.1111/apt.14577. Epub 2018 Feb 26.
PubMed 29479728
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients With Suboptimal Response Following Nucleos(t)Ide Therapy
- ClinicalTrials.gov ID
- NCT04201808
- Acronym / sponsor ID
- IN-CN-320-5556
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- New Discovery LLCIndustry (pharma, biotech, devices)
- Collaborators
- Beijing Ditan Hospital
- Study start
- 1 May 2021 (estimated)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 17 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are potent antiviral agents for hepatitis B virus (HBV) and recommended by the American Association for the Study of Liver Disease (AASLD) as well as the European Association for the Study of Liver (EASL) guidelines for the treatment of nucleos(t)ide therapy induced HBV resistance. However, it is not clear if chronic hepatitis B (CHB) patients with nucleos(t)ide treatment experience without genotypic mutations would be benefit from TAF therapy. Previous studies have observed that suboptimal response (SOR) following antiviral therapy with nucleos(t)ide treatment is associated with an increased risk of subsequent treatment failure and viral resistance. It remains unclear whether switching to TAF is a reasonable approach in patients with SOR to second-line antivirals Lamivudine (LAM)/ Telbivudine (LdT)/ Adefovir Dipivoxil (ADV) and its combinations with other second-line antivirals for 24 weeks, or SOR to the first-line antiviral Entecavir (ETV) or any antiviral combinations containing ETV for 48 weeks. This study is aimed to determine how the aforementioned patients with SOR to nucleos(t)ide treatment respond to TAF monotherapy. The investigator's study will provide evidence base for therapy selection in SOR patients, especially in China where the majority of patients with CHB are treated with nucleos(t)ide therapy.
Detailed description
This is a prospective, single-arm, multicenter cohort study evaluating the efficacy, safety, and tolerability of TAF monotherapy in in Asian CHB adults with SOR to the nucleos(t)ide therapy by assessing the HBV DNA suppression in 48 weeks. Approximately one hundred adults who received the aforementioned nucleos(t)ide therapy will be prospectively enrolled during the period from December 2019 to June 2021. Subjects will be enrolled by medical clinic in about 10 university centers in different regions in China. Approximately 10-15 consecutive eligible patients will be enrolled from each participating sites. This study will be conducted in accordance with the guidelines of Good Clinical Practices (GCPs) including Institutional Review Board (IRB) approval and consent will be applied. Patient identification (ID) will be de-identified for submitting to the central database for analyses from all study sites. Free TAF treatment will be provided to all enrolled patients for 48 weeks. Patients will be under the local standard of care upon the completion of the current study.
Patients aged 18-80 with CHB infection who had received nucleos(t)ide therapy over 24 weeks of LAM/LdT/ADV or 48 weeks of ETV with medication adherence, but failure to achieve the levels of HBV-DNA below 300 IU/mL will be eligible. Subjects will be excluded if they meet the following criteria: co-infected with HIV or other viral hepatitis; the serum levels of HBV DNA are too low (i.e. about 300 IU/mL) to be analyzed for the genotypic mutation(s); nucleos(t)ide resistant mutants have been detected at screening visit, patient is under a clinical research protocol of phase I-III development; unable to consent or unlikely to complete one year follow up after the enrollment; and other medical condition may affect the ability to participate the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is single-arm, multicenter cohort study evaluating the efficacy, safety, and tolerability of TAF monotherapy in Asian CHB adults with SOR to the nucleos(t)ide therapy by assessing the HBV DNA suppression over a duration of 48 weeks.
| Arm | Type | Receives |
|---|---|---|
| Single Arm Intervention Group | Experimental | Drug: Tenofovir Alafenamide 25 MGAll approximately 100 patients experienced previous suboptimal response to other direct acting antivirals. Patients must have received nucleos(t)ide therapy consisting of LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks with medication adherence. All patients in this study are in the same arm. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must be 18-80 years of age.
- Patients must have documented compensated and stable chronic hepatitis B defined by all of the following:
- Patients must have received nucleos(t)ide therapy consisting of LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks with medication adherence.
- Although having undergone therapy, patients have had failure to achieve the levels of HBV-DNA below 300 IU/mL.
- Patient is willing and able to comply with the study drug regimen and all other study requirements.
Key exclusion criteria (35 listed)
- Pregnant women, and women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
- Males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception.
- Unwilling and/or unable to provide written informed consent
- Patients with CHB but are also co-infected with HIV or other viral hepatitis
- Patients whose serum levels of HBV DNA are too low (i.e. about 300 IU/mL) to be analyzed for the genotypic mutation(s) at the onset of this trial, i.e. baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir Alafenamide 25 MGAlso: VemlidyAll patients will receive Tenofovir Alafenamide, 25mg PO, to treat chronic hepatitis B and their previous suboptimal response over the study duration of 48 weeks. Patients will be followed every 12 weeks for medication adherence, medication refill, and follow up as per standard of care. | Drug | Single Arm Intervention Group |
Primary outcome
this study seeks to evaluate the efficacy of TAF in Asian CHB adults with a proven SOR to previous nucleo(t)side therapy by assessing the percentage of patients who achieve HBV DNA viral suppression over a time span of 48 weeks.
Time frame: 48 weeks
In this study, HBV DNA viral suppression is defined as a HBV DNA level <20 IU/mL, and previous nucleo(t)side therapy is defined as treatments including LAM, LdT, ADV, and ETV before switching to TAF. The parameters for SOR will be set as patients who exhibit a 1 log10 IU/mL decrease in HBV DNA with medication adherence, but still present with an HBV DNA level of >300 IU/mL and has no detectable genotype mutation(s) when treated with the second-line antivirals LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or treated with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks.
7 secondary outcomes
Incidence of Treatment-Emergent Adverse Events in Patients as stratified by the CTCAE v 5.0
Time frame: At 12, 24, 36, and 48 weeks
Percentage of Patients Who Discontinue the Therapy Due to Issues with Tolerability
Time frame: At 12, 24, 36, and 48 weeks
Percentage of patients with Alanine transferase (ALT) levels within the normal limit
Time frame: 48 weeks
Percentage of patients with Aspartamine transferase (AST) levels within the normal limit
Time frame: 48 weeks
Percentage of patients who experience loss/seroconversion of HBsAg and/or HBeAg during the study.
Time frame: 48 weeks
Percentage of patients with detectable drug resistance mutations
Time frame: 48 weeks
Percentage of patients who have skipped TAF treatment during the study
Time frame: 48 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2020.
- Background: PubMed 29756595Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.
- Background: PubMed 28404092Buti 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.
- Background: PubMed 28427875European 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.
- Background: PubMed 25417914Lu L, Yip B, Trinh H, Pan CQ, Han SH, Wong CC, Li J, Chan S, Krishnan G, Wong CC, Nguyen MH. Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir. J Viral Hepat. 2015 Aug;22(8):675-81. doi: 10.1111/jvh.12368. Epub 2014 Nov 24.
- Background: PubMed 25987775Pan CQ, Chan S, Trinh H, Yao A, Bae H, Lou L. Similar efficacy and safety of tenofovir in Asians and non-Asians with chronic hepatitis B. World J Gastroenterol. 2015 May 14;21(18):5524-31. doi: 10.3748/wjg.v21.i18.5524.
- Background: PubMed 22329376Pan CQ, Hu KQ, Yu AS, Chen W, Bunchorntavakul C, Reddy KR. Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir. J Viral Hepat. 2012 Mar;19(3):213-9. doi: 10.1111/j.1365-2893.2011.01533.x. Epub 2011 Oct 17.
- Background: PubMed 29405329Terrault 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. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
- Background: PubMed 29479728Tong MJ, Pan CQ, Han SB, Lu DS, Raman S, Hu KQ, Lim JK, Hann HW, Min AD. An expert consensus for the management of chronic hepatitis B in Asian Americans. Aliment Pharmacol Ther. 2018 Apr;47(8):1181-1200. doi: 10.1111/apt.14577. Epub 2018 Feb 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Calvin Q Pan, MD principal investigator
NYU Langone Health
Wen Xie, MD study director
Capital Medical University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir Alafenamide 25 MG in people with Hepatitis B, Chronic, run by New Discovery LLC at 10 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wen Xie, MD ((+86) 13651113763, Xiewen6218@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
this study seeks to evaluate the efficacy of TAF in Asian CHB adults with a proven SOR to previous nucleo(t)side therapy by assessing the percentage of patients who achieve HBV DNA viral suppression over a time span of 48 weeks. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04201808, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2020.