Chronic Hepatitis bPhase 4NCT03241641
Switching From TDF to TAF vs. Maintaining TDF in Chronic Hepatitis B With Resistance to Adefovir or Entecavir.
A Phase 4 study testing Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate in people with Chronic Hepatitis b, run by Young-Suk Lim at 1 site in South Korea.
Trial summary
Treatment of CHB patients with genotypic resistance to NUCs has been problematic due to the lack of data from randomized trials. Recently, two randomized trials comparing the efficacy of TDF monotherapy versus TDF and ETV combination therapy in CHB patients with documented genotypic resistance to adefovir (ADV) or ETV… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Chronic Hepatitis b
- What is being tested?
- Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 1 siteSouth Korea
- Study dates
- 26 Oct 2017to 25 Mar 2021
- 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 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- Male or female, 20 to 80 years of age
- Compensated liver disease (Child-Pugh score < 8)
- HBsAg positive at least 6 months or more
- HBeAg positive or negative
- Confirmation of ETV resistance mutation (rt184, rtS202, or rtM250) at the enrollment of IN-US-174-0202 study, or ADV resistance mutation (rtA181V, rtA181T or rtN236T) at the enrollment of IN-US-174-0205 study
- Completion of the week 240 visit in studies IN-US-174-0202 or 0205 study and maintained on TDF 300 mg QD
- Patient is willing and able to comply with all study requirements
Who cannot join
- Co-infection with HCV, HDV, HIV
- Abusing alcohol (more than 40 g/day) or illicit drugs
- Abnormal hematological and biochemical parameters, including:
- 1) serum bilirubin >3 mg/dL 2) prothrombin time (INR) >1.5 3) serum albumin <2.8 g/dL 4) ascites, encephalopathy or variceal hemorrhage 5) Child-Pugh score ≥8
- 4. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
- 5. Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agent
Show all 14Show fewer
- 6. Received solid organ or bone marrow transplant
- 7. Known hypersensitivity to study drugs, metabolites, or formulation excipients
- 8. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study or unable to comply with dosing requirements
- 9. Use of investigational agents within 3 months of screening, unless allowed by the Sponsor or Investigator
- 10. A history of hepatocellular carcinoma (HCC) within 5 years of screening
- 11. A history treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years
- 12. Participation in another investigational drug trial
- 13. Pregnant or breastfeeding or willing to be pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Switching From Tenofovir Disoproxil Fumarate(TDF) to Tenofovir AlaFenamide(TAF) vs. Maintaining TDF Monotherapy in Chronic Hepatitis B Patients With Genotypic Resistance to Adefovir or Entecavir
Treatment of CHB patients with genotypic resistance to NUCs has been problematic due to the lack of data from randomized trials. Recently, two randomized trials comparing the efficacy of TDF monotherapy versus TDF and ETV combination therapy in CHB patients with documented genotypic resistance to adefovir (ADV) or ETV demonstrated TDF monotherapy was not statistically different in viral suppression at week 48 of treatment.1,2 The extension study based on the above two trials merged study subjects from these trials with changing from TDF and ETV combination group to TDF monotherapy to evaluate long-term efficacy and safety of TDF monotherapy for multidrug-resistant patients. At the time of merging of 192 subjects, by intention-to-treat analysis, 66.3% of TDF group and 68.0% of TDF-ETV group had virological response as determined by serum HBV DNA <15 IU/mL. (in press) Three year long-term follow up study showed that the proportion of virologic suppression increased to 76.8% and 72.2% in TDF-TDF and TDF/TDF-ETV groups, respectively( P=0.46). (in press)
TAF, a novel prodrug of tenofovir was developed to have greater stability in plasma than TDF, thereby enabling more efficient delivery of the active metabolite to target cells at a substantially lower dose. The reduced systemic exposure of tenofovir offers the potential for an improved safety profile compared to TDF a benefit that demonstrated in a recent clinical trial in patients with HIV infection. In a recent double-blind randomized phase 3 noninferiority trial with 873 treatment naive patients who were positive for HBeAg, the proportion of patients receiving TAF who had HBV DNA <29 IU/mL at week 48 was 64%, which was non-inferior to the rate of 67% in patients receiving TDF (P=0.25).3 In the safety profile, TAF group had significantly smaller decrease in BMD than TDF group in the hip and spine, as well as significantly smaller increases in serum creatinine at week 48.3 For treatment naive HBeAg negative patients, a recent study with 425 subjects applied the same methodology and showed noninferiority in efficacy of TAF compared to TDF at week 48.4 Considering noninferiority in efficacy and superior bone and renal safety from TAF, TAF might be considered preferred choice of NUC instead of TDF. However, it is still unknown whether TAF would show similar efficacy and safety profile in patients with multidrug-resistant CHB.
Read the detailed description
Study objectives The objective of this study is to evaluate whether efficacy, safety, and tolerability (including bone and renal outcomes) were non-inferior in patients switched to a tenofovir alafenamide (TAF), compared with patients who remained on tenofovir disoproxil fumarate (TDF).
Study procedures This is a randomized, active-controlled, open-label, multicenter study to evaluate safety and non-inferior efficacy of switching from TDF 300 mg QD to TAF 25 mg QD for 48 weeks in chronic hepatitis B patients who have genotypic resistance to Adefovir/Entecavir.
174 subjects who complete the previous IN-US-174-0202/0205 studies will be randomized in a 1:1 ratio (A:B) to receive either TAF 25 mg QD or TDF 300 mg QD Case group: approximately 87 subjects administered TAF 25 mg QD Control group: approximately 87 subjects administered TDF 300 mg QD
The primary analysis will occur at Week 48 with the primary efficacy endpoint being newly achievement and maintenance of virologic response (HBV DNA <60 IU/mL at Week 48).
The duration of maintaining both arms is 48 weeks. All subjects who complete 48 weeks of treatment are eligible for participation in the open label TAF 25 mg extension period for an additional 48 weeks (through Week 96)
- Conditions
- Chronic Hepatitis b
- Being tested
- Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate
- 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 AlafenamideDrug
Also called Vemlidy
25mg, Daily Oral
Tenofovir Disoproxil FumarateDrug
Also called Viread
300mg, Daily Oral
| Study group | Role | What they receive |
|---|---|---|
| Maintaining TAF monotherapy | Experimental | - Tenofovir AlaFenamide (Vemlidy) Tablet, 25mg, Daily Oral, 96 weeks Receives: Drug: Tenofovir Alafenamide |
| Switching from TDF to TAF | Active comparator | * Tenofovir Disoproxil Fumarate (Viread) Tablet, 300mg, Daily Oral, 48 weeks
* Tenofovir AlaFenamide (Vemlidy) Tablet, 25mg, Daily Oral, 48 weeks Receives: Drug: Tenofovir Alafenamide; Drug: Tenofovir Disoproxil Fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with virologic response
The proportion of patients who achieve virologic response (serum HBV DNA concentrations below 60 IU/mL)
Measured: At week 48 of treatment
Secondary outcomes (12)
Proportion of patients with virologic response
The proportion of patients who achieve virologic response (serum HBV DNA concentrations below 60 IU/mL)
Measured: At week 96 of treatment
The proportion of patients with HBV DNA less than 15 IU/mL
The proportion of patients with HBV DNA less than 15 IU/mL
Measured: At week 48, and 96 of treatment
The proportion of patients with normal ALT
The proportion of patients with normal ALT
Measured: At week 24, 48, 72 and 96 of treatment
The proportion of patients with HBeAg loss or seroconversion
The proportion of patients with HBeAg loss or seroconversion
Measured: At week 24, 48, 72 and 96 of treatment
The proportion of patients with HBsAg loss or seroconversion
The proportion of patients with HBsAg loss or seroconversion
Measured: At week 24, 48, 72 and 96 of treatment
The incidence of virologic breakthrough
Virologic breakthrough is defined as the increases in HBV DNA levels ≥1 log10IU/mL from nadir on two consecutive tests during continued treatment
Measured: At week 48, and 96 of treatment
The proportion of patients with resistance mutations to Entecavir or Adefovir or Tenofovir
The proportion of patients with resistance mutations to Entecavir or Adefovir or Tenofovir
Measured: At week 48, and 96 of treatment
Percentage change from baseline in hip and spine bone mineral density (BMD)
Percentage change from baseline in hip and spine bone mineral density (BMD)
Measured: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine beta2-microglobulin
Percentage change from baseline in urine beta2-microglobulin
Measured: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine protein to creatinine ratio
Percentage change from baseline in urine protein to creatinine ratio
Measured: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine albumin to creatinine ratio
Percentage change from baseline in urine albumin to creatinine ratio
Measured: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in serum creatinine
Percentage change from baseline in serum creatinine
Measured: At week 24, 48, 72 and 96 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2017
- Study start26 Oct 2017
- Primary completion25 Mar 2021
- Study completion25 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis bStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Young-Suk Lim
- Sponsor type
- University, hospital or other
- Collaborators
- Samsung Medical Center, Korea University Guro Hospital, Konkuk University Medical Center, Seoul National University Hospital
- Responsible party
- Sponsor-investigator, Young-Suk Lim, Asan Medical Center
- Investigators
- Young-Suk Lim, M.D.,Ph D., Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03241641
- Sponsor's protocol ID
- IN-US-320-4390
- Status last verified
- Mar 2021
- First submitted
- 3 Aug 2017
- Last updated
- 29 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chae HB, Kim JH, Kim JK, Yim HJ. Current status of liver diseases in Korea: hepatitis B. Korean J Hepatol. 2009 Dec;15 Suppl 6:S13-24. doi: 10.3350/kjhep.2009.15.S6.S13.
PubMed 20037275Kim SR, Kudo M, Hino O, Han KH, Chung YH, Lee HS; Organizing Committee of Japan-Korea Liver Symposium. Epidemiology of hepatocellular carcinoma in Japan and Korea. A review. Oncology. 2008;75 Suppl 1:13-6. doi: 10.1159/000173419. Epub 2008 Dec 17.
PubMed 19092267Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
PubMed 15470215Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
PubMed 16391218Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
PubMed 16530509Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Feb;51(2):422-30. doi: 10.1002/hep.23327.
PubMed 20049753Snow-Lampart A, Chappell B, Curtis M, Zhu Y, Myrick F, Schawalder J, Kitrinos K, Svarovskaia ES, Miller MD, Sorbel J, Heathcote J, Marcellin P, Borroto-Esoda K. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology. 2011 Mar;53(3):763-73. doi: 10.1002/hep.24078. Epub 2010 Dec 22.
PubMed 21374657Zoulim F, Durantel D, Deny P. Management and prevention of drug resistance in chronic hepatitis B. Liver Int. 2009 Jan;29 Suppl 1:108-15. doi: 10.1111/j.1478-3231.2008.01939.x.
PubMed 19207973Bartholomeusz A, Locarnini SA. Antiviral drug resistance: clinical consequences and molecular aspects. Semin Liver Dis. 2006 May;26(2):162-70. doi: 10.1055/s-2006-939758.
PubMed 16673294Lim YS, Yoo BC, Byun KS, Kwon SY, Kim YJ, An J, Lee HC, Lee YS. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial. Gut. 2016 Jun;65(6):1042-51. doi: 10.1136/gutjnl-2014-308435. Epub 2015 Mar 23.
PubMed 25800784Lim YS, Byun KS, Yoo BC, Kwon SY, Kim YJ, An J, Lee HC, Lee YS. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial. Gut. 2016 May;65(5):852-60. doi: 10.1136/gutjnl-2014-308353. Epub 2015 Jan 16.
PubMed 25596179Chan 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.
PubMed 28404091Buti 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 28404092Byun KS, Choi J, Kim JH, Lee YS, Lee HC, Kim YJ, Yoo BC, Kwon SY, Gwak GY, Lim YS. Tenofovir Alafenamide for Drug-Resistant Hepatitis B: A Randomized Trial for Switching From Tenofovir Disoproxil Fumarate. Clin Gastroenterol Hepatol. 2022 Feb;20(2):427-437.e5. doi: 10.1016/j.cgh.2021.04.045. Epub 2021 May 4.
PubMed 33962041
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching From Tenofovir Disoproxil Fumarate(TDF) to Tenofovir AlaFenamide(TAF) vs. Maintaining TDF Monotherapy in Chronic Hepatitis B Patients With Genotypic Resistance to Adefovir or Entecavir
- ClinicalTrials.gov ID
- NCT03241641
- Acronym / sponsor ID
- IN-US-320-4390
- Conditions
- Chronic Hepatitis b
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 174 participants (actual)
- Lead sponsor
- Young-Suk LimUniversity, hospital or other
- Collaborators
- Samsung Medical Center, Korea University Guro Hospital, Konkuk University Medical Center, Seoul National University Hospital
- Study start
- 26 Oct 2017 (actual)
- Primary completion
- 25 Mar 2021 (actual)
- Study completion
- 25 Mar 2021 (actual)
- First posted
- 7 Aug 2017 (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.
Treatment of CHB patients with genotypic resistance to NUCs has been problematic due to the lack of data from randomized trials. Recently, two randomized trials comparing the efficacy of TDF monotherapy versus TDF and ETV combination therapy in CHB patients with documented genotypic resistance to adefovir (ADV) or ETV demonstrated TDF monotherapy was not statistically different in viral suppression at week 48 of treatment.1,2 The extension study based on the above two trials merged study subjects from these trials with changing from TDF and ETV combination group to TDF monotherapy to evaluate long-term efficacy and safety of TDF monotherapy for multidrug-resistant patients. At the time of merging of 192 subjects, by intention-to-treat analysis, 66.3% of TDF group and 68.0% of TDF-ETV group had virological response as determined by serum HBV DNA <15 IU/mL. (in press) Three year long-term follow up study showed that the proportion of virologic suppression increased to 76.8% and 72.2% in TDF-TDF and TDF/TDF-ETV groups, respectively( P=0.46). (in press)
TAF, a novel prodrug of tenofovir was developed to have greater stability in plasma than TDF, thereby enabling more efficient delivery of the active metabolite to target cells at a substantially lower dose. The reduced systemic exposure of tenofovir offers the potential for an improved safety profile compared to TDF a benefit that demonstrated in a recent clinical trial in patients with HIV infection. In a recent double-blind randomized phase 3 noninferiority trial with 873 treatment naive patients who were positive for HBeAg, the proportion of patients receiving TAF who had HBV DNA <29 IU/mL at week 48 was 64%, which was non-inferior to the rate of 67% in patients receiving TDF (P=0.25).3 In the safety profile, TAF group had significantly smaller decrease in BMD than TDF group in the hip and spine, as well as significantly smaller increases in serum creatinine at week 48.3 For treatment naive HBeAg negative patients, a recent study with 425 subjects applied the same methodology and showed noninferiority in efficacy of TAF compared to TDF at week 48.4 Considering noninferiority in efficacy and superior bone and renal safety from TAF, TAF might be considered preferred choice of NUC instead of TDF. However, it is still unknown whether TAF would show similar efficacy and safety profile in patients with multidrug-resistant CHB.
Detailed description
Study objectives The objective of this study is to evaluate whether efficacy, safety, and tolerability (including bone and renal outcomes) were non-inferior in patients switched to a tenofovir alafenamide (TAF), compared with patients who remained on tenofovir disoproxil fumarate (TDF).
Study procedures This is a randomized, active-controlled, open-label, multicenter study to evaluate safety and non-inferior efficacy of switching from TDF 300 mg QD to TAF 25 mg QD for 48 weeks in chronic hepatitis B patients who have genotypic resistance to Adefovir/Entecavir.
174 subjects who complete the previous IN-US-174-0202/0205 studies will be randomized in a 1:1 ratio (A:B) to receive either TAF 25 mg QD or TDF 300 mg QD Case group: approximately 87 subjects administered TAF 25 mg QD Control group: approximately 87 subjects administered TDF 300 mg QD
The primary analysis will occur at Week 48 with the primary efficacy endpoint being newly achievement and maintenance of virologic response (HBV DNA <60 IU/mL at Week 48).
The duration of maintaining both arms is 48 weeks. All subjects who complete 48 weeks of treatment are eligible for participation in the open label TAF 25 mg extension period for an additional 48 weeks (through Week 96)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maintaining TAF monotherapy | Experimental | Drug: Tenofovir Alafenamide- Tenofovir AlaFenamide (Vemlidy) Tablet, 25mg, Daily Oral, 96 weeks |
| Switching from TDF to TAF | Active comparator | Drug: Tenofovir Alafenamide, Drug: Tenofovir Disoproxil Fumarate* Tenofovir Disoproxil Fumarate (Viread) Tablet, 300mg, Daily Oral, 48 weeks * Tenofovir AlaFenamide (Vemlidy) Tablet, 25mg, Daily Oral, 48 weeks |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
- Male or female, 20 to 80 years of age
- Compensated liver disease (Child-Pugh score < 8)
- HBsAg positive at least 6 months or more
- HBeAg positive or negative
Key exclusion criteria (14 listed)
- Co-infection with HCV, HDV, HIV
- Abusing alcohol (more than 40 g/day) or illicit drugs
- Abnormal hematological and biochemical parameters, including:
- 1) serum bilirubin >3 mg/dL 2) prothrombin time (INR) >1.5 3) serum albumin <2.8 g/dL 4) ascites, encephalopathy or variceal hemorrhage 5) Child-Pugh score ≥8
- 4. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
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 AlafenamideAlso: Vemlidy25mg, Daily Oral | Drug | Maintaining TAF monotherapy, Switching from TDF to TAF |
| Tenofovir Disoproxil FumarateAlso: Viread300mg, Daily Oral | Drug | Switching from TDF to TAF |
Primary outcome
Proportion of patients with virologic response
Time frame: At week 48 of treatment
The proportion of patients who achieve virologic response (serum HBV DNA concentrations below 60 IU/mL)
12 secondary outcomes
Proportion of patients with virologic response
Time frame: At week 96 of treatment
The proportion of patients with HBV DNA less than 15 IU/mL
Time frame: At week 48, and 96 of treatment
The proportion of patients with normal ALT
Time frame: At week 24, 48, 72 and 96 of treatment
The proportion of patients with HBeAg loss or seroconversion
Time frame: At week 24, 48, 72 and 96 of treatment
The proportion of patients with HBsAg loss or seroconversion
Time frame: At week 24, 48, 72 and 96 of treatment
The incidence of virologic breakthrough
Time frame: At week 48, and 96 of treatment
The proportion of patients with resistance mutations to Entecavir or Adefovir or Tenofovir
Time frame: At week 48, and 96 of treatment
Percentage change from baseline in hip and spine bone mineral density (BMD)
Time frame: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine beta2-microglobulin
Time frame: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine protein to creatinine ratio
Time frame: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in urine albumin to creatinine ratio
Time frame: At week 24, 48, 72 and 96 of treatment
Percentage change from baseline in serum creatinine
Time frame: At week 24, 48, 72 and 96 of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Results publication: PubMed 20037275Chae HB, Kim JH, Kim JK, Yim HJ. Current status of liver diseases in Korea: hepatitis B. Korean J Hepatol. 2009 Dec;15 Suppl 6:S13-24. doi: 10.3350/kjhep.2009.15.S6.S13.
- Results publication: PubMed 19092267Kim SR, Kudo M, Hino O, Han KH, Chung YH, Lee HS; Organizing Committee of Japan-Korea Liver Symposium. Epidemiology of hepatocellular carcinoma in Japan and Korea. A review. Oncology. 2008;75 Suppl 1:13-6. doi: 10.1159/000173419. Epub 2008 Dec 17.
- Results publication: PubMed 15470215Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
- Results publication: PubMed 16391218Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
- Results publication: PubMed 16530509Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
- Results publication: PubMed 20049753Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Feb;51(2):422-30. doi: 10.1002/hep.23327.
- Results publication: PubMed 21374657Snow-Lampart A, Chappell B, Curtis M, Zhu Y, Myrick F, Schawalder J, Kitrinos K, Svarovskaia ES, Miller MD, Sorbel J, Heathcote J, Marcellin P, Borroto-Esoda K. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology. 2011 Mar;53(3):763-73. doi: 10.1002/hep.24078. Epub 2010 Dec 22.
- Results publication: PubMed 19207973Zoulim F, Durantel D, Deny P. Management and prevention of drug resistance in chronic hepatitis B. Liver Int. 2009 Jan;29 Suppl 1:108-15. doi: 10.1111/j.1478-3231.2008.01939.x.
- Results publication: PubMed 16673294Bartholomeusz A, Locarnini SA. Antiviral drug resistance: clinical consequences and molecular aspects. Semin Liver Dis. 2006 May;26(2):162-70. doi: 10.1055/s-2006-939758.
- Results publication: PubMed 25800784Lim YS, Yoo BC, Byun KS, Kwon SY, Kim YJ, An J, Lee HC, Lee YS. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial. Gut. 2016 Jun;65(6):1042-51. doi: 10.1136/gutjnl-2014-308435. Epub 2015 Mar 23.
- Results publication: PubMed 25596179Lim YS, Byun KS, Yoo BC, Kwon SY, Kim YJ, An J, Lee HC, Lee YS. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial. Gut. 2016 May;65(5):852-60. doi: 10.1136/gutjnl-2014-308353. Epub 2015 Jan 16.
- Results publication: PubMed 28404091Chan 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.
- Individual participant dataSharing planned: No
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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.
Young-Suk Lim, M.D.,Ph D. principal investigator
Asan Medical Center
1 site 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 and Tenofovir Disoproxil Fumarate in people with Chronic Hepatitis b, run by Young-Suk Lim at 1 site in South Korea.
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 14 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: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with virologic response (time frame: At week 48 of treatment). 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 NCT03241641, which also lists 14 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 29 Mar 2021.