Clinical trial NCT05583006: Tenofovir Alafenamide Switch Therapy in Chronic Hepatitis B
Official title: A Prospective Cohort Study of Tenofovir Alafenamide Switch Therapy in Chronic Hepatitis B Patients Who Are Unsatisfied to Entecavir Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Patient Satisfaction
Drug Adherence
Efficacy, Self
Safety Issues
Lead sponsor: Taichung Veterans General Hospital
Sponsor class: OTHER
Collaborators: name: Institute of Adherence to Medication
First posted: 2022-10-17
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This prospective cohort study will enroll CHB patients who are unsatisfied to ETV therapy. The patient selection in this study is essentially based on a principle of shared decision making, and not only the physician decides whether to change the treatment. In the initial screening period, study subjects will be selected according to the inclusion and exclusion criteria, therefore only patients who complain the efficacy and/or inconvenience of ETV therapy (Inclusion criteria 4), will be invited to join this study. After discussing with the physician together, the study subjects must sign the inform consents before going into the next step (baseline condition evaluation).

Brief summary: Chronic hepatitis B (CHB) patients may be unsatisfied to entecavir (ETV) therapy due to the inconvenience in drug taking, i.e., fasting for more than 2 hours and/or dose adjustment according to estimated glomerular filtration rate (eGFR). However, tenofovir alafenamide (TAF) has been approved to be highly effective and safe in patients with CHB, and is convenient in drug taking, i.e., once daily regardless food taking and renal function.Therefore,TAF can be a good option in CHB patients who are unsatisfied to ETV therapy. The aim of this prospective cohort study is to assess the improvement on satisfaction (including drug adherence) of TAF switch therapy in CHB patients who are unsatisfied to ETV therapy. In addition, with expected adherence improvement in TAF switch therapy, the efficacy of TAF switch therapy may be improved, and the efficacy benefits can be evaluated by the changes of some novel biomarkers, such as HBV core-related antigen (HBcrAg). The investigators therefore aim to conduct a prospective cohort study of TAF switch therapy for CHB patients who are unsatisfied to ETV therapy.

Detailed description: Although nucleos(t)ide analogue (NA) therapy can effectively suppress HBV replication, the ideal therapeutic endpoints, including hepatitis B surface antigen(HBsAg) seroclearance, is difficult to achieve.(1) Therefore, chronic hepatitis B (CHB) patients often require long-term HBV suppression to achieve the therapeutic goals, with the adherence to long-term NA therapy being an important clinical issue.(2, 3) ETV is one of the standard treatments for CHB,(4, 5) but its absorption can be significantly reduced by food.(6) ETV users must take the pills two hours before or after meals, and the blood level of ETV may thus be affected if this recommendation is not fully followed.In addition, the metabolism of ETV is involved by renal excretion, therefore the dosage of ETV should be adjusted according to renal function.(7) For example, among patients in chronic kidney disease (CKD) stage 4, i.e.,eGRF15-29 ml/min/1.73m, the frequency of ETV taking should be reduced from once daily to every 72-96 hours, which may be forgettable and inconvenient to ETV users.However, the adherence of NA therapy is an essential part for long-term HBV suppression, and the efficacy of ETV therapy may be affected by the reduced adherence during long-term therapy.

Except ETV, TAF is also a HBV antiviral recommended by the current practice guidelines in the treatment of CHB, with a high potency in antiviral efficacy and low rate in virological resistance.(4, 5) In addition, TAF can be a 2nd-line rescue antiviral recommendation for HBV with resistance to ETV therapy.(4, 5) Moreover, because TAF is formulated to deliver the active metabolite to target cells more efficiently than tenofovir disoproxil fumarate (TDF) at a much lower dose, thereby reducing systemic exposure to tenofovir. In the randomized controlled trials,(8, 9) patients in the TAF arm had improved renal function and bone marrow density (BMD),as compared to patients in the TDF arm. Furthermore, in some retrospective studies, switching from ETV to TAF may present a superior efficacy in HBV DNA suppression and HBsAg level reduction,(10-13) and renal safety was comparable between the TAF switch group and the ETV continuation group.(10, 11) Interestingly, switching from ETV to TAF is associated with improvement of the medication adherence,(6) which may be particularly important to patients under long-term NA therapy.

In a small retrospective study conducted in Japan,(14) medication adherence and satisfaction were compared between before and after switch antiviral therapy in patients who switched to TAF from ETV (n = 15), and medication adherence was found to be significantly improved (P = 0.04). In a prospective study aimed to evaluate the changes of serum HBsAg levels during a 48-week period after switching ETV to TAF,(6) the degree of HBsAg reduction was higher during the TAF administration period than during the ETV administration period in patients without cirrhosis, with genotype B HBV, or with undetectable serum hepatitis B core-related antigen (HBcrAg).The HBV cccDNA-related biomarkers, such as quantitative HBsAg (qHBsAg) or HBcrAg, have been considered important outcome predictors.(15, 16) With expected adherence improvement in TAF switch therapy, the changes of above-mentioned biomarkers may be improved. The investigators therefore aim to conduct a prospective cohort study of TAF switch therapy for CHB patients who are unsatisfied to ETV therapy.

Eligibility criteria: Inclusion Criteria:

1. At least 20 years of age
2. Detectable serum HBsAg
3. Chronic HBV infection under ETV therapy
4. ETV users who are unsatisfied with the efficacy and/or feel inconvenient of ETV therapy
5. No contraindications for TAF switch therapy
6. HBV antiviral period expectancy for at least 1 year

Exclusion Criteria:

1. End stage renal disease (estimated glomerular filtration rate \[eGRF\]\< 15 mL/min/1.73m2) without dialysis
2. Co-infected with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
3. Any active malignancies
4. Under immunosuppressants
5. Known allergy to tenofovir-contained regimens

Primary outcomes:
measure: Rate/ concentration of renal function markers
timeFrame: week 48
measure: HBV viral load
timeFrame: week 48
measure: The satisfaction (including drug adherence) to TAF switch therapy
timeFrame: week 48
Secondary outcomes:
measure: Rate/ concentration of renal function markers
timeFrame: week 144
measure: HBV viral load
timeFrame: week 144
measure: The satisfaction (including drug adherence) to TAF switch therapy
timeFrame: week 144
measure: Concentration of biochemical markers
timeFrame: week 144
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: Taichung Veterans General Hospital
name: Teng-Yu Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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