Clinical trial NCT03471624: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Keywords: Tenofovir alafenamide (TAF)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2018-03-20
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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):

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With HBV DNA <20 IU Per mL
timeFrame: Baseline, 6, 12, 18, 24 months
Secondary outcomes:
measure: Number of Participants With Normal Alanine Aminotransferase (ALT).
timeFrame: Baseline, 6, 12, 18, 24 months
measure: Calculated eGFR
timeFrame: Baseline, 6, 12, 18, 24 months
measure: The Mean Bone Mass Density (T-score) Change
timeFrame: Baseline, month 24
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Nagoya
country: Japan
facility: Nagoya City University
city: Osaka
country: Japan
facility: Osaka City University
city: Saga
country: Japan
facility: Saga University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Nowon Eulji Medical Center, Eulji University College of Medicine,
city: Seoul
country: Korea, Republic of
facility: Sanggye Paik Hospital, Inje University College of Medicine
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: Stanford University
name: Mindie H Nguyen, MD,MAS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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, 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.