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

NCT03471624 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 45054
• Study Type: interventional
• Target: 270
• Locations: 4 countries
• Sites: 12

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

Conditions

Hepatitis B, Chronic

Keywords

Tenofovir alafenamide (TAF)

Outcome Measures

Primary Outcomes (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.

  Baseline, 6, 12, 18, 24 months

Secondary Outcomes (3)

• Number of Participants With Normal Alanine Aminotransferase (ALT).

  Baseline, 6, 12, 18, 24 months

• Calculated eGFR

  Baseline, 6, 12, 18, 24 months

• The Mean Bone Mass Density (T-score) Change

  Baseline, month 24

Study Arms (1)

Tenofovir Alafenamide for 24 months

EXPERIMENTAL

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.

Drug: Tenofovir Alafenamide

Interventions

Tenofovir Alafenamide DRUG

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).

Also known as: Vemlidy

Tenofovir Alafenamide for 24 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Gilead Sciences: collaborator

Study Sites (12)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

San Jose Gastroenterology

San Jose, California, 95128, United States

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Nagoya City University

Nagoya, 467-8601, Japan

Location

Osaka City University

Osaka, 545-8585, Japan

Location

Saga University Hospital

Saga, 849-8501, Japan

Location

Hanyang University Seoul Hospital

Seoul, 04736, South Korea

Location

Nowon Eulji Medical Center, Eulji University College of Medicine,

Seoul, South Korea

Location

Sanggye Paik Hospital, Inje University College of Medicine

Seoul, South Korea

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

E-Da Hospital

Kaohsiung City, 82445, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

Related Publications (8)

• 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.

  PMID: 26188135 BACKGROUND

• 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.

  PMID: 26566246 BACKGROUND

• 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.

  PMID: 26231459 BACKGROUND

• 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.

  PMID: 18802412 BACKGROUND

• 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.

  PMID: 22532028 BACKGROUND

• 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.

  PMID: 26563120 BACKGROUND

• 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.

  PMID: 29405329 BACKGROUND

• 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.

  PMID: 37882252 RESULT

Related Links

• Vemlidy package insert

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mindie H Nguyen, Professor of Medicine, GI & Hepatology, Liver Transplant
• Organization: Stanford University

mindiehn@stanford.edu

650-498-6084

Study Officials

• Mindie H Nguyen, MD,MAS

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Profesor of Medicine

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 20, 2018
• Study Start: May 1, 2018
• Primary Completion: April 19, 2022
• Study Completion: April 19, 2022
• Last Updated: November 18, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-11

Locations

KR (3); JP (4); US (2); TW (3)