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

Hepatitis B, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03471624
• Other study ID #: 45054
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2018
• Est. completion date: April 19, 2022

Study information

• Verified date: November 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: April 19, 2022
• Est. primary completion date: April 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Male or female, age =18 years

2. Chronic hepatitis B diagnosis confirmed by positive HBsAg or HBV DNA or HBeAg or documented history of chronic hepatitis B in physician note

3. 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

4. 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).

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Tenofovir Alafenamide
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).

Locations

Country	Name	City	State
Japan	Kyushu University Hospital	Fukuoka
Japan	Nagoya City University	Nagoya
Japan	Osaka City University	Osaka
Japan	Saga University Hospital	Saga
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Nowon Eulji Medical Center, Eulji University College of Medicine,	Seoul
Korea, Republic of	Sanggye Paik Hospital, Inje University College of Medicine	Seoul
Taiwan	E-Da Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
United States	Stanford University Medical Center	Palo Alto	California
United States	San Jose Gastroenterology	San Jose	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Gilead Sciences

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of,  Taiwan, 

References & Publications (8)

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. — View 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. — View Citation

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, Nguye — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Baseline, 6, 12, 18, 24 months
Secondary	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]a × [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, a is -0.329 for females and -0.411 for males	Baseline, 6, 12, 18, 24 months
Secondary	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.	Baseline, month 24

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