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Hepatitis B, ChronicPhase 4NCT03471624

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

A Phase 4 study testing Tenofovir Alafenamide in people with Hepatitis B, Chronic, run by Stanford University at 12 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis B, Chronic
What is being tested?
Tenofovir Alafenamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
12 sitesin 4 countries
Study dates
1 May 2018to 19 Apr 2022
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 10Show fewer
  • 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

Trial locations and contacts

12 sites in 4 countries.

12 sites in 4 countries

Japan4 sites

  • Kyushu University Hospital

    Fukuoka, 812-8582

  • Nagoya City University

    Nagoya, 467-8601

  • Osaka City University

    Osaka, 545-8585

  • Saga University Hospital

    Saga, 849-8501

Other trials in Japan

South Korea3 sites

  • Hanyang University Seoul Hospital

    Seoul, 04736

  • Nowon Eulji Medical Center, Eulji University College of Medicine,

    Seoul

  • Sanggye Paik Hospital, Inje University College of Medicine

    Seoul

Other trials in South Korea

Taiwan3 sites

  • Kaohsiung Medical University Hospital

    Kaohsiung City, 807

  • E-Da Hospital

    Kaohsiung City, 82445

  • China Medical University Hospital

    Taichung

Other trials in Taiwan

United States2 sites

  • Stanford University Medical Center

    Palo Alto, California, 94304

  • San Jose Gastroenterology

    San Jose, California, 95128

Other trials in United States

About this study

Primary Objective:

To describe rate of persistence and/or improvement of viral suppression with TAF as with previous anti-HBV (hepatitis B virus) treatment

Read the detailed description

Secondary Objective(s):

  1. Describe persistence of ALT (alanine aminotransferase) normalization and/or improvement of ALT levels with TAF as with previous anti-HBV treatment
  2. To describe trends in serum creatinine and calculated creatinine clearance as available by local labs.
  3. To describe trends in bone mass from baseline to 24 months after switch. https://med.stanford.edu/nguyenlab/clinical-trials.html
Being tested
Tenofovir Alafenamide
Keywords
Tenofovir alafenamide (TAF)
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

    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).

Study groups in NCT03471624
Study groupRoleWhat they receive
Tenofovir Alafenamide for 24 monthsExperimentalParticipants 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.
Receives: Drug: Tenofovir Alafenamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, 6, 12, 18, 24 months

Secondary outcomes (3)

  1. 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

    Measured: Baseline, 6, 12, 18, 24 months

  2. 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

    Measured: Baseline, 6, 12, 18, 24 months

  3. 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.

    Measured: Baseline, month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2018
  2. Study start1 May 2018
  3. Primary completion19 Apr 2022
  4. Study completion19 Apr 2022

Resources

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
Masking
None (open label)
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03471624
Sponsor's protocol ID
45054
Status last verified
Nov 2023
First submitted
7 Mar 2018
Last updated
18 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 26188135

  • 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.

    PubMed 26566246

  • 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.

    PubMed 26231459

  • 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.

    PubMed 18802412

  • 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.

    PubMed 22532028

  • 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.

    PubMed 26563120

  • 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.

    PubMed 29405329

  • Ogawa E, Jun DW, Toyoda H, Hsu YC, Yoon EL, Ahn SB, Yeh ML, Do S, Trinh HN, Takahashi H, Enomoto M, Kawada N, Yasuda S, Tseng CH, Kawashima K, Lee HA, Inoue K, Haga H, Do AT, Maeda M, Hoang JH, Cheung R, Ueno Y, Eguchi Y, Furusyo N, Yu ML, Tanaka Y, Nguyen MH. Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study. Aliment Pharmacol Ther. 2024 Jan;59(2):239-248. doi: 10.1111/apt.17785. Epub 2023 Oct 26.

    PubMed 37882252

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tenofovir Alafenamide in people with Hepatitis B, Chronic, run by Stanford University at 12 sites in 4 countries.

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 7 inclusion and 10 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 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Japan, South Korea, Taiwan, United States. 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?

Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With HBV DNA <20 IU Per mL (time frame: Baseline, 6, 12, 18, 24 months). 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 NCT03471624, 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 18 Nov 2023.

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