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Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)

Primary Purpose

Hepatitis B, Chronic

Status
Active
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Tenofovir Alafenamide
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Tenofovir alafenamide (TAF)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Male or female, age ≥18 years
  2. CHB (chronic hepatitis B) diagnosis confirmed by positive HBsAg or HBV DNA or HBeAg or documented history of CHB in physician note
  3. Currently maintained on antiviral therapy for at least 48 weeks with any HBV DNA value at Screening/Baseline and planned to be switched to TAF by their physician
  4. Routinely monitored for serum HBV DNA PCR (polymerase chain reaction), liver chemistry including AST (aspartate aminotransferase )/ALT/total bilirubin, renal chemistry including BUN (blood urea nitrogen)/Cr/CO2 (carbon dioxide) by their physicians every 3-6 months and a bone density scan at least every 2 years as per routine clinical care (one at baseline and one 2 years after switch).
  5. Estimated creatinine clearance > 15 ml/min (using the Cockcroft-Gault method) at Screening/Baseline Visit. (Note: multiply estimated rate by 0.85 for women).
  6. Willing and able to provide informed consent
  7. Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion criteria:

  1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
  2. Previous recipient of a liver transplant
  3. Co-infection with human immunodeficiency virus (HIV) or hepatitis C (HCV) or hepatitis D (HDV)
  4. Severe or uncontrolled comorbidities
  5. Current or known hepatic decompensation (≤2 years) (e.g ascites, encephalopathy, or variceal hemorrhage) with a Child-Pugh score of B or C
  6. Malignancy including liver cancer within 5 years except cancers curable by surgical resection (e.g. basal cell skin cancer and squamous cell cancer)
  7. On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 11). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening/Baseline visit.
  8. Males and females of reproductive potential who are unwilling to use "effective" protocol-specified method(s) of contraception during the study.
  9. Current substance or alcohol abuse judged by the investigator to potentially interfere with subject compliance.
  10. Any other clinical conditions that, in the opinion of the Investigator, would make the subject unsuitable or unable to comply with any of the study procedures

Sites / Locations

  • Stanford University Medical Center
  • San Jose Gastroenterology
  • Kyushu University Hospital
  • Nagoya City University
  • Osaka City University
  • Saga University Hospital
  • Hanyang University Seoul Hospital
  • Nowon Eulji Medical Center, Eulji University College of Medicine,
  • Sanggye Paik Hospital, Inje University College of Medicine
  • Kaohsiung Medical University Hospital
  • E-Da Hospital
  • China Medical University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tenofovir Alafenamide for 24 months

Arm Description

Participants on any antiviral treatment for chronic HBV who plan to be switched by their physician to be treated with TAF 25 mg for 24 months.

Outcomes

Primary Outcome Measures

Number of Participants With HBV DNA <20 IU Per mL
To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment.

Secondary Outcome Measures

Number of Participants With Normal Alanine Aminotransferase (ALT).
Alanine aminotransferase (ALT) normalization is defined if ALT was less than 35 U/L for men or 25 U/L for women
Calculated eGFR
To describe trends in calculated eGFR as available by local labs. Estimated glomerular filtration rates (eGFR) were calculated using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation (eGFR [mL∕min∕1.73m2] =141 × [minimum Scr∕K, 1]α × [maximum Scr/K, 1]1.209 × 0.993age × 1.018 [if female] × 1.159 [if black]) where Scr is serum creatinine in µmol/L, K is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males
The Mean Bone Mass Density (T-score) Change
To describe trends in bone mass density from baseline to end of study. Bone Mass Density(BMD) was evaluated using T-score of Lumber-spine. The T-score is a comparison of the results to a average peak bone mass of healthy young adult. 0 indicates healthy young adult's mean with a SD of 1. Normal BMD was defined with T-score of -1.0 or above; osteopenia with T-score between -1.1 and -2.4, and osteoporosis with T-score of -2.5 or below (ref). Worsened BMD was defined by upstaging of BMD class from normal to osteopenia or worse or from osteopenia to osteoporosis. Improved BMD was defined by downstaging of BMD class from osteopenia to normal or osteoporosis to osteopenia or normal.

Full Information

First Posted
March 7, 2018
Last Updated
June 13, 2023
Sponsor
Stanford University
Collaborators
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03471624
Brief Title
Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)
Official Title
Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
April 19, 2022 (Actual)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary Objective: To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV (hepatitis B virus) treatment
Detailed Description
Secondary Objective(s): Describe persistence of ALT (alanine aminotransferase) normalization and/or improvement of ALT levels with TAF as with previous anti-HBV treatment To describe trends in serum creatinine and calculated creatinine clearance as available by local labs. To describe trends in bone mass from baseline to 24 months after switch. https://med.stanford.edu/nguyenlab/clinical-trials.html

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Tenofovir alafenamide (TAF)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
270 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tenofovir Alafenamide for 24 months
Arm Type
Experimental
Arm Description
Participants on any antiviral treatment for chronic HBV who plan to be switched by their physician to be treated with TAF 25 mg for 24 months.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Alafenamide
Other Intervention Name(s)
Vemlidy
Intervention Description
Tenofovir alafenamide (TAF) is a new formulation of tenofovir with higher intracellular active drug concentration allowing for dosing of only 25 mg once daily and thus can potentially lower the already low risk of renal toxicity and bone loss with tenofovir disoproxil fumarate (TDF).
Primary Outcome Measure Information:
Title
Number of Participants With HBV DNA <20 IU Per mL
Description
To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV treatment.
Time Frame
Baseline, 6, 12, 18, 24 months
Secondary Outcome Measure Information:
Title
Number of Participants With Normal Alanine Aminotransferase (ALT).
Description
Alanine aminotransferase (ALT) normalization is defined if ALT was less than 35 U/L for men or 25 U/L for women
Time Frame
Baseline, 6, 12, 18, 24 months
Title
Calculated eGFR
Description
To describe trends in calculated eGFR as available by local labs. Estimated glomerular filtration rates (eGFR) were calculated using the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation (eGFR [mL∕min∕1.73m2] =141 × [minimum Scr∕K, 1]α × [maximum Scr/K, 1]1.209 × 0.993age × 1.018 [if female] × 1.159 [if black]) where Scr is serum creatinine in µmol/L, K is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males
Time Frame
Baseline, 6, 12, 18, 24 months
Title
The Mean Bone Mass Density (T-score) Change
Description
To describe trends in bone mass density from baseline to end of study. Bone Mass Density(BMD) was evaluated using T-score of Lumber-spine. The T-score is a comparison of the results to a average peak bone mass of healthy young adult. 0 indicates healthy young adult's mean with a SD of 1. Normal BMD was defined with T-score of -1.0 or above; osteopenia with T-score between -1.1 and -2.4, and osteoporosis with T-score of -2.5 or below (ref). Worsened BMD was defined by upstaging of BMD class from normal to osteopenia or worse or from osteopenia to osteoporosis. Improved BMD was defined by downstaging of BMD class from osteopenia to normal or osteoporosis to osteopenia or normal.
Time Frame
Baseline, month 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Male or female, age ≥18 years Chronic hepatitis B diagnosis confirmed by positive HBsAg or HBV DNA or HBeAg or documented history of chronic hepatitis B in physician note Currently maintained on antiviral therapy for at least 48 weeks with any Hepatitis B virus(HBV) DNA value at Screening/Baseline and planned to be switched to TAF by their physician Routinely monitored for serum HBV DNA Polymerase chain reaction(PCR), liver chemistry including Aspartate aminotransferase (AST )/alanine transaminase(ALT)/total bilirubin, renal chemistry including Blood urea nitrogen(BUN)/Creatinine/Carbon dioxide (CO2) by their physicians every 3-6 months and a bone density scan at least every 2 years as per routine clinical care (one at baseline and one 2 years after switch). Estimated creatinine clearance > 15 ml/min (using the Cockcroft-Gault method) at Screening/Baseline Visit. (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 breastfeeding or who believe they may wish to become pregnant during the course of the study Previous recipient of a liver transplant Co-infection with human immunodeficiency virus (HIV) or hepatitis C (HCV) or hepatitis D (HDV) Severe or uncontrolled comorbidities Current or known hepatic decompensation (≤2 years) (e.g ascites, encephalopathy, or variceal hemorrhage) with a Child-Pugh score of B or C Malignancy including liver cancer within 5 years except cancers curable by surgical resection (e.g. basal cell skin cancer and squamous cell cancer) On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 11). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening/Baseline visit. Males and females of reproductive potential who are unwilling to use "effective" protocol-specified method(s) of contraception during the study. Current substance or alcohol abuse judged by the investigator to potentially interfere with subject compliance. Any other clinical conditions that, in the opinion of the Investigator, would make the subject unsuitable or unable to comply with any of the study procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mindie H Nguyen, MD,MAS
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
San Jose Gastroenterology
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Nagoya City University
City
Nagoya
ZIP/Postal Code
467-8601
Country
Japan
Facility Name
Osaka City University
City
Osaka
ZIP/Postal Code
545-8585
Country
Japan
Facility Name
Saga University Hospital
City
Saga
ZIP/Postal Code
849-8501
Country
Japan
Facility Name
Hanyang University Seoul Hospital
City
Seoul
ZIP/Postal Code
04736
Country
Korea, Republic of
Facility Name
Nowon Eulji Medical Center, Eulji University College of Medicine,
City
Seoul
Country
Korea, Republic of
Facility Name
Sanggye Paik Hospital, Inje University College of Medicine
City
Seoul
Country
Korea, Republic of
Facility Name
Kaohsiung Medical University Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
E-Da Hospital
City
Kaohsiung
ZIP/Postal Code
82445
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
26188135
Citation
Martin P, Lau DT, Nguyen MH, Janssen HL, Dieterich DT, Peters MG, Jacobson IM. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. Clin Gastroenterol Hepatol. 2015 Nov;13(12):2071-87.e16. doi: 10.1016/j.cgh.2015.07.007. Epub 2015 Jul 15.
Results Reference
background
PubMed Identifier
26566246
Citation
Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016 Jan;63(1):284-306. doi: 10.1002/hep.28280. Epub 2015 Nov 13.
Results Reference
background
PubMed Identifier
26231459
Citation
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.
Results Reference
background
PubMed Identifier
18802412
Citation
Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW; Centers for Disease Control and Prevention (CDC). Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008 Sep 19;57(RR-8):1-20.
Results Reference
background
PubMed Identifier
22532028
Citation
Ward JW, Byrd KK. Hepatitis B in the United States: a major health disparity affecting many foreign-born populations. Hepatology. 2012 Aug;56(2):419-21. doi: 10.1002/hep.25799. No abstract available.
Results Reference
background
PubMed Identifier
26563120
Citation
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.
Results Reference
background
PubMed Identifier
29405329
Citation
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. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
Results Reference
background
Links:
URL
https://www.gilead.com/~/media/files/pdfs/medicines/liver-disease/vemlidy/vemlidy_pi.pdf?la=en
Description
Vemlidy package insert

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Treatment Outcomes in Chronic Hepatitis B Patients on Sequential Therapy With Tenofovir Alafenamide (TAF)

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