Clinical trial NCT03566030: Switching From Tenofovir Disoproxi Fumarate to Tenofovir Alafenamide in Chronic Hepatitis B Patients With Antiviral Resistance
Official title: Real-life Data of Switching From Tenofovir Disoproxi Fumarate (TDF) to Tenofovir Alafenamide (TAF) in Virologically Suppressed Chronic Hepatitis B Patients With Antiviral Resistance
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis B
Antiviral Drug Adverse Reaction
Keywords: Hepatitis B
Tenofovir Disoproxil Fumarate
Tenofovir Alafenamide
Switch
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2018-06-21
Enrollment: 300
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The investigators will conduct a multicenter observational study to evaluate the safety and efficacy of TAF 25 mg QD in chronic hepatitis B patients with antiviral resistance who switch from TDF to TAF. Subjects will be obtained from an existing cohort of patients treated with a TDF-based regimen due to antiviral resistance, which has been supported by Gilead (IN-US-174-1255).

Brief summary: * To evaluate the efficacy of switching to tenofovir alafenamide (TAF) 25 mg QD versus continued tenofovir disoproxil fumarate (TDF) 300 mg QD in CHB patients with antiviral resistance, as determined by the proportion of virologically suppressed patients at week 48
* To evaluate the safety and tolerability of switching to TAF 25 mg QD versus continuing TDF 300 mg QD in antiviral-resistant subjects with chronic HBV at week 48

Detailed description: The investigators will conduct a multicenter observational study to evaluate the safety and efficacy of TAF 25 mg QD in chronic hepatitis B patients with antiviral resistance who switch from TDF to TAF. The safety and antiviral activity will be assessed as a part of routine medical care. Subjects will be obtained from an existing cohort of patients treated with a TDF-based regimen due to antiviral resistance, which has been supported by Gilead (IN-US-174-1255).

It is anticipated that approximately 300 CHB patients with antiviral resistance taking TDF 300 mg QD will be enrolled in this study. All consecutive patients will be allocated to receive either TAF 25 mg QD or TDF 300 mg QD (possibly 50% vs. 50%, the proportion of patients enrolled in the study is an estimate based on the clinical experience.), according to the decision of the individual patients and their physicians, with informed consent. Patients are switched independently based on physicians discretion/decision prior to study enrollment, and the study protocol would NOT have any influence over the process.

All consecutive patients will be prospectively monitored every 6 months during the first year and thereafter every 6 months up to 3 years. At each visit, a routine examination and determination of biochemical and virological parameters (HBV DNA level, HBeAg, anti-HBe, HBsAg \[quantitatively, if available\], and anti-HBs) will be performed. Lab tests and markers will be routinely monitored every 6 months.

Recruitment method: In this study, we plan to use an existing cohort of patients treated with a TDF-based regimen due to antiviral resistance (IN-US-174-1255). Data on all consecutive patients currently receiving TDF due to antiviral resistance at enrollment will be followed up prospectively every 3-6 months for 2 years. The patients will be recruited consecutively. Patients will be recruited only after the treatment decision has been made. No aspect of this study will interfere with or influence routine medical practice.

Number of study sites: At least seven representative institutes in South Korea. Target population: Korean adult subjects with CHB receiving TDF due to antiviral resistance.

Eligibility criteria: Inclusion Criteria:

* Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
* Adult male and non-pregnant, non-lactating female subjects, ≥20 years of age based on the date of the screening visit.
* Documented evidence of chronic HBV infection previously
* TDF monotherapy, TDF-based combination therapy, or switching to TAF at least 4 weeks prior to screening in virologically suppressed chronic hepatitis B patients with multi-antiviral resistance
* Must be willing and able to comply with all study requirements

Exclusion Criteria:

• Co-infection with HCV, HDV, HIV

Primary outcomes:
measure: Serum HBV DNA level
timeFrame: at week 48
Secondary outcomes:
measure: Serum HBV DNA level
timeFrame: at week 96
measure: Hip and spine BMD
timeFrame: at 48, 96 week
measure: Serum eGFR
timeFrame: at 24, 48, 72, and 96 week
measure: Serum creatinine & PO4 level
timeFrame: at 24, 48, 72, and 96 week
Other outcomes:
Locations:
Study officials:
References: